Clinical Trials In Cancer Patients Research Articles

Implementing an educational resource for patients participating in cancer clinical trials during the pandemic.

This research is centred in the specialty of early phase cancer research - the branch of clinical research that focuses on phase one and phase two clinical trials. The aim was to gain an understanding of the complexity of work involved in implementing an educational intervention within the clinical pathway for newly referred early phase cancer clinical trial patients. The May and Finch Normalisation Process Theory (NPT) was used to understand, develop and evaluate the process of embedding an educational resource at referral hospital sites. Elements emerged from the evaluation that provide insights into the complexity of the implementation work that took place. The main elements were: pandemic-related challenges, change management, leadership, shared purpose, teamwork, workforce capacity and patient outcomes. The findings shed light on the barriers to or facilitators of the implementation of the educational resource.

Abstract PO5-20-05: The FOR ME (Fostering Opportunities in Research through Messaging and Education) study: Using multiple qualitative methods to develop a culturally sensitive narrative intervention to promote equity in clinical trials

Abstract Background: Black women are more likely to present with advanced stage disease and to die following a breast cancer (BC) diagnosis compared to women from other racial/ethnic groups. In 2020, only 7.2% of enrollees in clinical trials that led to the approval of 3 novel drugs for breast cancer were Black. While there are many contributing factors to this inequity (i.e., tumor biology, social and structural health determinants, racial injustice, and differential access to and utilization of high-quality mammography, diagnostics, and therapies), persistent underrepresentation of Black patients in cancer clinical trials (CTs) slows scientific advancements. Objective: The aim of this study is to develop, optimize, and test a narrative decision aid intervention (web-based video) for Black women diagnosed with BC to promote shared decision making and CT participation. The first aim is to conduct multiple qualitative methods with multi-level stakeholders to identify barriers, facilitators, and intervention priorities that would assist Black breast cancer patients to make informed decisions about participating in clinical trials. The second aim is to create a culturally sensitive, narrative intervention designed to support decision making and motivate Black breast cancer patients to participate in clinical trials. Aim 3 will then pilot a study to determine acceptability of the intervention among patients and assess whether it increases clinical trial participation in a safety net oncology practice. Methods: Guided by community-based participatory research approaches, we used multiple qualitative methods (key informant interviews (KIIs) and story circles) to identify barriers and facilitators that support decision-making and CT participation. The KIIs, completed in-person, via phone, or video conferencing, were recorded and professionally transcribed. The research team used thematic analysis and inductive coding approaches. Next, interviews and focus groups will invite feedback on the educational/motivational content of the intervention and will be used to develop a culturally sensitive script and story boards. A video production company will produce the narrative intervention. Finally, focus groups and interviews with participant cohorts will provide feedback on the completed intervention. Black women diagnosed with BC will view the intervention in an oncology clinic. Using a pretest/posttest design, we will analyze the acceptability of the intervention and its effect on intention to participate in clinical trials. We will then conduct a quasi-experimental study in a safety net oncology practice to determine whether the rate of clinical trial participation among Black breast cancer patients increases following implementation of the intervention as a standard component of new patient education. Progress: Recruitment started in July 2022 and currently 30 of 30 interviews with patients are completed, 20 of 20 interviews with clinical stakeholders (oncologists and clinical trial staff) are completed, and 14 of 20 interviews with advocates and community partners are completed. Data collection and the analysis of the interviews and story circles is ongoing. Citation Format: Neha Hippalgaonkar, Ryan Nguyen, Leslie Carnahan, Vida Henderson, Tigist Mersha, Eliza Cohn, Kauthar Salum, Ana Williams, Lolita Coleman, Beulah Brent, AnneMarie Murphy, Paris Thomas, Paramjeet Khosla, Kent Hoskins. The FOR ME (Fostering Opportunities in Research through Messaging and Education) study: Using multiple qualitative methods to develop a culturally sensitive narrative intervention to promote equity in clinical trials [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-20-05.

Broadening Eligibility Criteria and Diversity among Patients for Cancer Clinical Trials

BackgroundCertain populations have been historically underrepresented in clinical trials. Broadening eligibility criteria is one approach to inclusive clinical research and achieving enrollment goals. How broadened trial eligibility criteria affect the diversity of eligible participants is unknown.MethodsUsing a nationwide electronic health record–derived deidentified database, we identified a retrospective cohort of patients diagnosed with 22 cancer types between April 1, 2013 and December 31, 2022 who received systemic therapy (N=235,234) for cancer. We evaluated strict versus broadened eligibility criteria using performance status and liver, kidney, and hematologic function around first line of therapy. We performed logistic regression to estimate odds ratios for exclusion by strict criteria and their association with measures of patient diversity, including sex, age, race or ethnicity, and area-level socioeconomic status (SES); estimated the impact of broadening criteria on the number and distribution of eligible patients; and performed Cox regression to estimate hazard ratios for real-world overall survival (rwOS) comparing patients meeting strict versus broadened criteria.ResultsWhen applying common strict cutoffs for eligibility criteria to patients with complete data and weighting each cancer type equally, 48% of patients were eligible for clinical trials. Female (odds ratio, 1.30; 95% confidence interval [CI], 1.25 to 1.35), older (age 75+ vs. 18 to 49 years old: odds ratio, 3.04; 95% CI, 2.85 to 3.24), Latinx (odds ratio, 1.46; 95% CI, 1.39 to 1.54), non-Latinx Black (odds ratio, 1.11; 95% CI, 1.06 to 1.16), and lower-SES patients were more likely to be excluded using strict eligibility criteria. Broadening criteria increased the number of eligible patients by 78%, with the strongest impact for older, female, non-Latinx Black, and lower-SES patients. Patients who met only broadened criteria had worse rwOS versus those with strict criteria (hazard ratio, 1.31; 95% CI, 1.27 to 1.34).ConclusionsData-driven evaluation of clinical trial eligibility criteria may optimize the eligibility of certain historically underrepresented groups and promote access to more inclusive trials. (Sponsored by Flatiron Health.)

Abstract 6722: A CD33 antigen targeted Gamma Delta T-cell engager in combination with zoledronate promotes Vg9Vd2+ T cell proliferation and cytotoxicity against acute myeloid leukemia

Abstract Vγ9Vδ2+ T cell (GDT) targeted immunotherapy is of interest to harness its MHC-independent cytotoxic potential to promote anti-tumor immunity. However, it remains unclear whether GDT (1-5% of total T cells) are present at sufficient numbers to be therapeutically relevant. Accumulation of intracellular phosphoantigens promotes heterodimerization of butyrophilin (BTN) 2A1 and BTN3A1 on the cell surface, leading to TCR-mediated activation of GDT. To date, clinical trials in cancer patients have failed to demonstrate monotherapy activity using a variety of GDT activating agents, including aminobisphosphonates such as zoledronic acid (ZA), Vδ2+ targeted T cell engagers and BTN3A1 targeted antibodies. These data leave fundamental questions regarding the therapeutic potential of GDT unanswered, including whether they are present in sufficient numbers, whether the agents in question are providing adequate GDT activation, and whether GDT are being directed to tumor cell targets. The studies herein were thus designed to further understand the role of phosphoantigens, butyrophilins and antigen presenting cells (APCs) in activating GDT. Specifically, APC mediated GDT activation was studied in an in vitro co-culture system in the presence and absence of ZA or a CD33-directed GDT engager incorporating a heterodimer of BTN2A1 and BTN3A1 to dissect the contribution of phosphoantigens, butyrophilins and other costimulatory molecules on GDT proliferation and activation. To this end, while BTN2A1/3A1-Fc-CD33scFv treatment alone in T and monocyte-derived dendritic cell (mDC) co-cultures or in unfractionated PBMCs increased the frequency of GDT by 2 to 10-fold after 7-12 days, the combination with low dose ZA (0.5 to 2 μM) synergistically increased GDT proliferation by 40 to 100-fold. These results indicate that GDT proliferation relies both on the abundance of BTN2A1/3A1 heterodimers and other costimulatory signals activated by ZA. Synergistic effects of ZA and BTN2A1/3A1-Fc-CD33scFv in GDT proliferation was similarly observed in human PBMC-engrafted NSG-IL-15tg mice 12 days after treatment. Importantly, the addition of BTN2A1/3A1-Fc-CD33scFv to T (or PBMC) and CD33+ AML co-cultures enhanced both GDT proliferation and anti-leukemic activity while sparing healthy CD33+ immune cells. Collectively, these results demonstrate that GDT proliferation and effector function is dependent both upon the abundance of butyrophilin heterodimers, and other cell surface molecules which are modulated by intracellular phosphoantigen accumulation. Citation Format: Anne Y. Lai, Chunyan Wang, Dana C. Baiu, Kelsey Smith, Arpita Patel, Kinsley Evans, Noah Murr, Derek Franklin, Mahmud Hussain, Joseph Pate, Nathan Oien, Vishruti Makani, Abhinav Shukla, Keith Wilson, George Fromm, Taylor H. Schreiber, Jenny E. Gumperz, Suresh De Silva. A CD33 antigen targeted Gamma Delta T-cell engager in combination with zoledronate promotes Vg9Vd2+ T cell proliferation and cytotoxicity against acute myeloid leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6722.

Abstract 3920: BND-35, a novel anti-ILT3 antibody for remodulation of the tumor microenvironment

Abstract Background: ILT3 (LILRB4) is expressed in various suppressive myeloid cells including tumor associated macrophages (TAM), myeloid derived suppressor cells (MDSCs) and tolerogenic dendritic cells (DCtol). The binding of ILT3 to its ligands induces an immunosuppressive phenotype in myeloid cells, mediates the inhibition of T cells activity and generates an immunosuppressive tumor microenvironment (TME) which supports tumor growth. The inhibition of ILT3 can restore the anti-tumor activity of myeloid cells and T cells, and thus remodulate the TME from immunosuppressive to pro-inflammatory. Here we describe preclinical characterization of BND-35, a humanized IgG4, ILT3 antagonist antibody developed for the treatment of solid tumors. Methods: BND-35 binding to ILT3 was evaluated by flow cytometry, ELISA and surface plasmon resonance. We investigated the ability of BND-35 to block ILT3 interactions with APOE and fibronectin, to enhance the pro inflammatory activity of various myeloid cells and reverse ILT3-mediated immune suppression of T cells by different suppressive myeloid cells using ELISA and in vitro and ex vivo cell-based assays. The anti-tumor activity of BND-35 was also evaluated in vivo in hILT3 transgenic mouse tumor models as well as in tumoroid systems generated from cancer patients. Results: BND-35 binds ILT3, but not other ILT-family receptors, with low nanomolar affinity and blocks its interaction with APOE and fibronectin in a concentration-dependent manner. ILT3 blockade with BND-35 restored the pro-inflammatory activity of FcR-stimulated DCs and THP1 cells inhibited by fibronectin. BND-35 was also shown to restore an M1 phenotype in cancer patients’ derived monocytes differentiated in the presence of autologous tumor cells. In addition, BND-35 restored T cell activity (both, CD4 and CD8 T cells) inhibited by either DCtol, MDSCs or M2 cells as a single agent and in combination with anti PD-1. BND-35 enhanced immune activity in a unique system of patient-derived tumoroids as evidenced by the secretion of pro-inflammatory cytokines. In vivo, blocking ILT3 activity with BND-35 resulted in decreased tumor growth and induced a pro-inflammatory phenotype in tumor resident T cells and myeloid cells populations as a single agent and in combination with anti PD-1. Conclusions: BND-35 is an anti-ILT3 antagonist antibody that was shown to induce potent pro inflammatory activity of myeloid cells and enhance T cells activity inhibited by ILT3 expressing myeloid suppressive cells in multiple in vitro, ex vivo and in vivo models. By doing so, BND-35 can lead to TME remodelling from immunosuppressive to proinflammatory. Safety, tolerability, and anti-tumor activity of BND-35 will be explored in a first-in-human clinical trial in cancer patients with solid tumors. Citation Format: Tsuri Peretz, Yoav Pizem, Liat Iancovici, Ella Peled, Motti Hakim, Sharon Hashmueli, Ilana Mandel, Yair Sapir, Tehila Ben Moshe. BND-35, a novel anti-ILT3 antibody for remodulation of the tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3920.

Abstract 1002: The historically black colleges and universities cancer trial consortium: A way forward to diversifying cancer clinical trials

Abstract The National Comprehensive Cancer Center Network cancer guidelines state that the best management for a cancer patient is on a clinical trial. However, the demographics of 74 registration trials for oral cancer therapies from 2009 - 2019 show only 2.5% of participating patients were Black. Similarly, of the 3,593 patients enrolled in all registration trials for new cancer drugs approved by the FDA in 2019, only 4% were Black patients. A third analysis showed that between 2008 and 2018, only 3.1% of cancer trial patients were Black. The underrepresentation of Black patients in cancer clinical trials is a complex issue that requires a multifaceted solution. Complicated, interdependent causes include, but are not limited to system, provider, and patient bias. Increasing globalization of clinical trials also contributes to a widening gap in Black patient enrollment. Achieving diversity among clinical trial participants requires intention in study design regarding accrual sites and outreach, and involvement of a diverse trial workforce. The ideal clinical trial system would minimize system, provider, and patient biases. Such a system already exists in the Historically Black Colleges and Universities (HBCU) system. HBCUs represent 3% of institutions of higher education in the USA, yet they enroll 16% of Black students and confer 24% of all baccalaureate degrees earned by Black students. 40% of Black engineers, 50% of Black lawyers, 70% of Black physicians, and a staggering 80% of Black judges attended an HBCU. HBCUs are exceptional at impacting communities of Color and have been doing so for centuries. The HBCU Cancer Trials Consortium (HBCU CTC) is a network of HBCUs and Ally institutions that aims to bring innovative cancer clinical trials to historically underserved communities and honor the legacy of HBCUs, which have consistently and successfully served underserved communities for over a century. The HBCU CTC will oversee and conduct cancer clinical trials at member institutions. We envision founding flagship members to include HBCUs that provide graduate medical education and training, such as Howard, Meharry, Charles Drew, and Morehouse. Non-HBCUs committed to the mission are invited to join the consortium as Ally institutions (eg. MSIs). Membership is not exclusive of membership in other cancer consortia. The HBCU CTC will provide shared resource services for member institutions that lack expertise or funding to conduct services locally (eg. data management, DSMB, biostatistics, a cancer focused IRB, central radiology, and central pathology). The Consortium will also work to develop local infrastructure support for the conduct of cancer clinical trials at member institutions. Citation Format: Sheldon L. Holder, Robert A. Winn, Wafik S. El-Deiry. The historically black colleges and universities cancer trial consortium: A way forward to diversifying cancer clinical trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1002.

Identification of a Gene Signature That Predicts Dependence upon YAP/TAZ-TEAD.

Targeted therapies are effective cancer treatments when accompanied by accurate diagnostic tests that can help identify patients that will respond to those therapies. The YAP/TAZ-TEAD axis is activated and plays a causal role in several cancer types, and TEAD inhibitors are currently in early-phase clinical trials in cancer patients. However, a lack of a reliable way to identify tumors with YAP/TAZ-TEAD activation for most cancer types makes it difficult to determine which tumors will be susceptible to TEAD inhibitors. Here, we used a combination of RNA-seq and bioinformatic analysis of metastatic melanoma cells to develop a YAP/TAZ gene signature. We found that the genes in this signature are TEAD-dependent in several melanoma cell lines, and that their expression strongly correlates with YAP/TAZ activation in human melanomas. Using DepMap dependency data, we found that this YAP/TAZ signature was predictive of melanoma cell dependence upon YAP/TAZ or TEADs. Importantly, this was not limited to melanoma because this signature was also predictive when tested on a panel of over 1000 cancer cell lines representing numerous distinct cancer types. Our results suggest that YAP/TAZ gene signatures like ours may be effective tools to predict tumor cell dependence upon YAP/TAZ-TEAD, and thus potentially provide a means to identify patients likely to benefit from TEAD inhibitors.

Psychological status of advanced cancer patients in clinical trials during the COVID-19 epidemic

Psychological status of advanced cancer patients in clinical trials during the COVID-19 epidemic

Abstract A060: “If it’s something that I can do for my future generations…”: Using multiple qualitative methods to inform an intervention to promote shared decision making and participation in clinical trials among Black women diagnosed with breast cancer

Abstract Background: Black women are more likely to present with advanced stage disease and to die following a breast cancer (BC) diagnosis compared to women from other racial/ethnic groups. While there are many contributing factors to this inequity (i.e., tumor biology, social and structural health determinants, racial injustice, and differential access to and utilization of high-quality mammography, diagnostics and therapies), persistent underrepresentation of Black patients in cancer clinical trials (CTs) slows scientific advancements. Objective: The goal of the FOR ME (Fostering Opportunities in Research through Messaging and Education) Study is to develop, optimize, and test a narrative decision aid intervention (web-based video) for Black women diagnosed with BC to promote shared decision making and CT participation. Here, we report on the development phase, wherein our objective was to identify salient themes and to understand lived experiences to enhance authenticity and to inform video content. Methods: Guided by community-based participatory research approaches, we used multiple qualitative methods (key informant interviews (KIIs) and story circles) to identify barriers and facilitators that support decision-making and CT participation. The KIIs, completed in-person, via phone, or video conferencing, were recorded and professionally transcribed. The research team used thematic analysis and inductive coding approaches. First, a subset of transcripts was annotated, then annotations were compiled into a preliminary codebook. Inter-coder reliability testing is ongoing to improve quality and to refine the codebook. The analysis team is using Dedoose, to analyze quotations and code co-occurrences, application frequencies, and relationships. Data collection and analysis of the story circles is ongoing. Results: In total, 30 Black women with BC participated in KIIs. Interviewees ranged in age from 27 to 75 years (M=59 + 12 years); concerning insurance, 63% had a public and 33% had a private source. About 27% were currently receiving BC treatment and 27% had prior CT participation. Participants expressed both positive and negative perceptions of CTs, sometimes concurrently. Barriers to CT participation included competing responsibilities, logistical burdens, ineffective provider communication, a lack of knowledge of CTs, individual and systemic racism, CT burdensome characteristics (invasive, potential for side effects), and comorbidities. Facilitators to CT participation included strong patient-provider communication and relationships, CT non-burdensome characteristics (non-invasive, minimal side effects), having a sense that participation benefits future generations, increased understanding of the CT, and feeling empowered in decision-making .Conclusion: To promote health equity in CTs, interventions should promote strong culturally sensitive patient-provider communication with emphasis on shared decision-making and patient empowerment along with emphasis on benefits toward future generations to promote a willingness to participate in CTs. Citation Format: Leslie R Carnahan, Vida Henderson, Tigist Mersha, Neha Hippalgaonkar, Ryan Nguyen, Eliza B Cohn, Kauthar Salum, Ana Williams, Lolita Coleman, Beulah Brent, AnneMarie Murphy, Paris Thomas, Paramjeet Khosla, Kent Hoskins. “If it’s something that I can do for my future generations…”: Using multiple qualitative methods to inform an intervention to promote shared decision making and participation in clinical trials among Black women diagnosed with breast cancer [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A060.

Development and psychometric evaluation of item banks for memory and attention – supplements to the EORTC CAT Core instrument

BackgroundCancer patients may experience a decrease in cognitive functioning before, during and after cancer treatment. So far, the Quality of Life Group of the European Organisation for Research and Treatment of Cancer (EORTC QLG) developed an item bank to assess self-reported memory and attention within a single, cognitive functioning scale (CF) using computerized adaptive testing (EORTC CAT Core CF item bank). However, the distinction between different cognitive functions might be important to assess the patients’ functional status appropriately and to determine treatment impact. To allow for such assessment, the aim of this study was to develop and psychometrically evaluate separate item banks for memory and attention based on the EORTC CAT Core CF item bank.MethodsIn a multistep process including an expert-based content analysis, we assigned 44 items from the EORTC CAT Core CF item bank to the memory or attention domain. Then, we conducted psychometric analyses based on a sample used within the development of the EORTC CAT Core CF item bank. The sample consisted of 1030 cancer patients from Denmark, France, Poland, and the United Kingdom. We evaluated measurement properties of the newly developed item banks using confirmatory factor analysis (CFA) and item response theory model calibration.ResultsItem assignment resulted in 31 memory and 13 attention items. Conducted CFAs suggested good fit to a 1-factor model for each domain and no violations of monotonicity or indications of differential item functioning. Evaluation of CATs for both memory and attention confirmed well-functioning item banks with increased power/reduced sample size requirements (for CATs ≥ 4 items and up to 40% reduction in sample size requirements in comparison to non-CAT format).ConclusionTwo well-functioning and psychometrically robust item banks for memory and attention were formed from the existing EORTC CAT Core CF item bank. These findings could support further research on self-reported cognitive functioning in cancer patients in clinical trials as well as for real-word-evidence. A more precise assessment of attention and memory deficits in cancer patients will strengthen the evidence on the effects of cancer treatment for different cancer entities, and therefore contribute to shared and informed clinical decision-making.

Abstract 17843: Direct Oral Anticoagulants versus Low Molecular Weight Heparin for Venous Thromboembolism in Cancer Patients: An Updated Systematic Review and Meta-Analysis

Introduction: Patients with cancer have an increased risk of venous thromboembolism (VTE). We aim to evaluate the risk of recurrent VTE and major bleeding in patients with cancer when started on DOACs versus low molecular weight heparin (LMWH). Methods: We conducted a systematic literature search according to PRISMA guidelines to identify studies using the terms: “venous thromboembolism,” “low molecular weight heparin,” and “direct oral anticoagulants.” After the screening, We extracted the data until May 2023 in a data extraction sheet. Our inclusion criteria were: adult patients, and cancer patients, who were on DOACs or LMWH for VTE or atrial fibrillation. We used a variance-weighted random-effects model to analyze data on DOACs vs. LMWH, estimating event rates and odds ratios while assessing heterogeneity. Data were analyzed using the ‘meta’ package in R. Results: Our analysis included 16 studies (n= 12216 patients). Cancer patients on DOACs significantly reduced the risk of recurrent VTEs compared to LMWHs OR 0.69 (95% CI: 0.56- 0.86, I 2:23% ). However, for major bleeding and clinically relevant non-major bleeding, although the statistical significance was not reached, a consistent trend favoring DOACs was observed (OR = 0.92, 95% CI: 0.65-1.30) and OR=1.19 (0.90-1.59) respectively. (Figure1) Conclusions: Among cancer patients, DOACs are associated with a significantly lower risk of recurrent VTEs than LMWHs. Although the statistical significance was not reached for major bleeding and clinically relevant non-major bleeding, there was a trend favoring DOACs over VKA. Increased recruitment of cancer patients in clinical trials is needed to provide us with updated data to refine treatment strategies.

Status and influential factors of spiritual well-being in cancer patients with drug clinical trials: a cross-sectional study.

The purpose of this study was to investigate the spiritual well-being status of cancer patients in drug clinical trials and its influencing factors, and to provide theoretical support for the spiritual health intervention of clinical trial cancer patients. This cross-section study was conducted among 244 cancer patients in clinical trials. The Memorial Symptom Assessment Scale Short Form (MSAS-SF), Connor-Davidson Resilience Scale 10 (CD-RISC 10), and Functional Assessment of Chronic Illness Therapy-Spiritual (FACIT-SP-12) were used to measure symptom burden, psychological resilience, and spiritual well-being. The Multiple Linear Regression Model was used to determine the influencing factors of patients' spiritual health. The overall spiritual health level of cancer patients with clinical trials was high (36.87 ± 11.0), and the spiritual health level was positively correlated with psychological resilience (r = 0.872, P < 0.001). Religious belief, nationality, treatment regimen, and resilience were independent risk factors for the spiritual health of cancer patients in clinical trials. Patients with religious beliefs (β = 0.097, P = 0.012), ethnic minorities (β = 0.087, P = 0.023), and high resilience scores (β = 0.874, P < 0.001) had higher levels of spiritual health. Patients who received single antineoplastic therapy (β = - 0.079, P = 0.028) had lower levels of spiritual health. Our study found that the spiritual health of cancer patients in clinical trials was at a high level, superior to cancer patients receiving conventional anti-tumor therapy. Religious belief, nationality, treatment regimen, and psychological resilience were the influential factors of spiritual health.

Intratumoral injection of melatonin enhances tumor regression in cell line-derived and patient-derived xenografts of head and neck cancer by increasing mitochondrial oxidative stress

Head and neck squamous cell carcinoma present a high mortality rate. Melatonin has been shown to have oncostatic effects in different types of cancers. However, inconsistent results have been reported for in vivo applications. Consequently, an alternative administration route is needed to improve bioavailability and establish the optimal dosage of melatonin for cancer treatment. On the other hand, the use of patient-derived tumor models has transformed the field of drug research because they reflect the heterogeneity of patient tumor tissues. In the present study, we explore mechanisms for increasing melatonin bioavailability in tumors and investigate its potential as an adjuvant to improve the therapeutic efficacy of cisplatin in the setting of both xenotransplanted cell lines and primary human HNSCC. We analyzed the effect of two different formulations of melatonin administered subcutaneously or intratumorally in Cal-27 and SCC-9 xenografts and in patient-derived xenografts. Melatonin effects on tumor mitochondrial metabolism was also evaluated as well as melatonin actions on tumor cell migration. In contrast to the results obtained with the subcutaneous melatonin, intratumoral injection of melatonin drastically inhibited tumor progression in HNSCC-derived xenografts, as well as in patient-derived xenografts. Interestingly, intratumoral injection of melatonin potentiated CDDP effects, decreasing Cal-27 tumor growth. We demonstrated that melatonin increases ROS production and apoptosis in tumors, targeting mitochondria. Melatonin also reduces migration capacities and metastasis markers. These results illustrate the great clinical potential of intratumoral melatonin treatment and encourage a future clinical trial in cancer patients to establish a proper clinical melatonin treatment.

Rates of and Factors Associated With Patient Withdrawal of Consent in Cancer Clinical Trials

Patient withdrawal of consent from a cancer clinical trial is defined as a patient's volitional cessation of participation in all matters related to a trial. It can undermine the trial's purpose, make the original sample size and power calculations irrelevant, introduce bias between trial arms, and prolong the time to trial completion. To report rates of and baseline factors associated with withdrawal of consent among patients in cancer clinical trials. This multisite observational cohort study was conducted through the Alliance for Clinical Trials in Oncology. Patient withdrawal was defined as a patient's voluntary termination of consent to participate anytime during trial conduct. Baseline patient- and trial-based factors were investigated for their associations with patient withdrawal within the first 2 years using logistic regression models. All patients who participated in cancer therapeutic clinical trials conducted within the Alliance for Clinical Trials in Oncology from 2013 through 2019 were included. The data lock date was January 23, 2022. The percentage of patients who withdrew consent in 2 years and factors associated with withdrawal of consent. A total of 11 993 patients (median age, 62 years; 67% female) from 58 trials were included. Within 2 years, 1060 patients (9%) withdrew from their respective trials. Two-year rates of withdrawal were 5.7%, 7.6%, 8.5%, 7.8%, 8.4%, 9.5%, and 9.8% for each of the respective years from 2013 through 2019. In multivariable analyses, Hispanic ethnicity (odds ratio [OR], 1.67; 95% CI, 1.30-2.15; P < .001), randomized design with placebo (OR, 1.64; 95% CI, 1.38-1.94; P < .001), and patient age 75 years and older (OR, 1.39; 95% CI, 1.12-1.72; P = .003) were associated with higher likelihood of withdrawal by 2 years. Use of radiation was associated with patient retention (OR, 0.68; 95% CI, 0.54-0.86; P = .001). In this cohort study, rates of withdrawal of consent were less than 10% and appeared consistent over time. Factors that are associated with withdrawal of consent should be considered when designing trials and should be further studied to learn how they can be favorably modified.

Patient communication and experiences in cancer clinical drug trials: a mixed-method study at a specialist clinical trials unit

BackgroundAs cancer therapies increase in their complexity, effective communication among patients, physicians, and research staff is critical for optimal clinical trial management. Currently, we understand little about on-trial communication practices and patient trial experiences over time. This mixed-method study explored patient experiences of participating in a clinical drug trial at different time points, focussing on patient communication with trial staff.MethodsPatients enrolled in clinical drug trials conducted at the Parkville Cancer Clinical Trials Unit were invited to complete a tailored online survey and/or a qualitative interview. Patients were recruited to three cohorts based on time since the first trial treatment: new (≥ 1 to ≤ 13 weeks), mid- (≥ 14 to ≤ 26 weeks), and long-term (≥ 52 weeks) trial patients. Descriptive statistics were calculated for survey responses. Interview data were analysed thematically with a team-based approach. Survey and interview data were integrated at the intepretation stage.ResultsFrom May to June 2021, 210 patients completed a survey (response rate 64%, 60% male), 20 completed interviews (60% male), and 18 completed both. More long-term trial patients (46%) participated than new (29%) and mid-trial patients (26%). Survey data showed high (> 90%) patient satisfaction with the provision of trial information and communication with trial staff across trial stages, and many reported trial experiences as above and beyond standard care. Interview data indicated that written trial information could be overwhelming, and verbal communication with the staff and physicians was highly valued, especially for enrolment and side effect management among long-term patients. Patients described the key points along the clinical trial trajectory that merit close attention: clear and well-communicated randomisation practices, reliable pathways for side effect reporting and prompt response from the trial staff, and end-of-trial transition management to avoid a sense of abandonment.ConclusionPatients reported high overall satisfaction with trial management but outlined key pinch points requiring improved communication practices. Establishing a range of effective communication practices among trial staff and physicians with patients in cancer clinical trials may have a wide range of positive effects on patient accrual, retention, and satisfaction.

Cost savings and clinical outcomes in cancer patients enrolled in clinical trials from a national public health system perspective.

e18813 Background: Clinical research has led to great advances that have an impact on improving the survival and quality of life of cancer patients and should be part of the standard of care. However, there is no clear evidence on whether participation in clinical trials (CTs) is cost-efficient for the national health system. For this reason, in the present study I have tried to analyse the direct impact of participation in CTs in terms of improvement in clinical results and costs. Particularly, I have looked into CT subjects diagnosed with metastatic renal cell carcinoma (mRCC) or G1-G2 metastatic neuroendocrine tumors (mNET). In addition, the potential influence of different prognostic and demographic factors on these variables has also been evaluated. Methods: Retrospectively, clinical data of the patients related to their baseline characteristics and the efficacy of the different lines of treatment they had received for their tumor were collected, as well as the direct healthcare costs derived from the clinical approach of all patients diagnosed with mRCC or mNET and clinically followed by the Ramón y Cajal University Hospital Medical Oncology Service, in Madrid, Spain, between January 2010 and February 2017. Subsequently, a comparative statistical analysis was performed of the results obtained in patients included in a clinical trial versus those who never participated in one but instead received therapy according to the standard of care (SOC). Results: Of the 104 patients (65 mRCC and 39 mNET) who were eventually included, 39 participated in a clinical trial. Overall, the 39 CT patients presented a higher overall survival (OS) than SOC patients (52 vs. 15 months. HR: 0.41; 95% CI: [0.23; 0.71]; p &lt; 0.01), a finding that carried through in all subgroups, including age, sex and prognostic factors. Regarding healthcare costs, patients who participated in CT yielded a mean annual savings of €46,109.56 per patient (p &lt; 0.01) compared to patients treated according to SOC, mainly due to pharmacological savings (€27,406.42). Furthermore, the savings were generalized in all subgroups regardless of age, sex and prognostic factors. Additionally, CT patients required 75.81% fewer hospitalisations (p &lt; 0.01) with a lower associated mean cost (p = 0.02), and the mean annual cost corresponding to the use of the Emergency Service was lower (p &lt; 0.01). Finally, the unadjusted incremental cost-effectiveness ratio (ICER) was -€14,970.64 per year of life gained (YLG) and the adjusted ICER was -€42,656.11 per life saved. Conclusions: From the national health system perspective, the participation of patients in CTs is related to an improvement in OS and savings in clinical costs in patients diagnosed with mRCC and mNET. In short, the participation of cancer patients in CTs represents a cost-efficient therapeutic option.

Association between state Medicaid policies and accrual of Black and Hispanic patients to cancer clinical trials.

1510 Background: The U.S. Medicaid health insurance program may play a key role in mitigating racial and ethnic disparities in cancer clinical trial enrollment, given Medicaid’s disproportionate representation of these populations and its coverage of the routine costs of trial participation in some states. We sought to evaluate the effect of Medicaid expansion under the Affordable Care Act (ACA) on changes in the accrual of racial and ethnic minority patients in cancer clinical trials, across all states and specifically those mandating Medicaid coverage of routine trial costs. Methods: The study used anonymous enrollment data from Medidata Rave, a large commercial clinical trial data collection platform. We conducted a retrospective difference-in-differences (DID) analysis to examine accrual demographics in states that expanded Medicaid eligibility under the ACA compared with non-expansion states, before and after expansion; and assessed effect modification based on state-mandated Medicaid coverage of routine trial costs. Participants included adults enrolled in interventional cancer clinical trials from 2012-2019, located in U.S. hospital referral regions with &gt;5% Black or Hispanic population. The primary outcome was participant race/ethnicity, defined dichotomously as Black or Hispanic (vs non-Black, non-Hispanic). We used ordinary least squares regression to model participant race/ethnicity as a function of (1) an indicator for trial enrollment in an expansion state after policy implementation, (2) state fixed effects, and (3) year fixed effects, with standard errors clustered at the state level. To assess effect modification, we stratified the main model across states with and without coverage mandates of routine trial costs. Results: The study included 75,700 participants across 1,409 clinical trials and 351 sites. In expansion states, the proportion of participants who identified as Black and/or Hispanic increased from 13.4% before expansion to 13.8% after expansion (0.4 percentage-point [PP] change, 95% CI -0.8 to 1.7). In non-expansion states, this proportion decreased from 17.0% to 15.2% (-1.7 PP change, 95% CI -3.7 to 0.2). These trends yielded a non-significant DID estimate of 2.0 PP (95% CI -1.0 to 5.0). In stratified analyses, Medicaid expansion was associated with a 4.5 PP (95% CI 0.4 to 8.6) increase in the enrollment of Black and/or Hispanic participants in states with coverage mandates, but not in states without coverage mandates (1.1 PP, 95% CI -2.6 to 4.8). Conclusions: Medicaid expansion was associated with a significant increase in the proportion of Black and Hispanic oncology trial participants in states that mandated Medicaid coverage of the routine costs of trial participation, but not overall across all states. These findings suggest that Medicaid policies have the potential to advance equitable enrollment in cancer clinical trials.

Implications of IL-21 in solid tumor therapy.

Cancer, the most deadly disease, is known as a recent dilemma worldwide. Presently different treatments are used for curing cancers, especially solid cancers. Because of the immune-enhancing functions of cytokine, IL-21 as a cytokine may have new possibilities to manipulate the immune system in disease conditions, as it stimulates NK and CTL functions and drives IgG antibody production. Indeed, IL-21 has been revealed to elicit antitumor-immune responses in several tumor models. Combining IL-21 with other agents, which target tumor cells, immune-regulatory circuits, or other immune-enhancing molecules enhances this activity. The exciting breakthrough in the results obtained in pre-clinical situations has led to the early outset of present developing clinical trials in cancer patients. In the paper, we have reviewed the function of IL-21 in solid tumor immunotherapy.

Abstract 972: VISTA expression in patients with advanced solid tumors: A potential biomarker in VISTA-101 clinical trial

Abstract V-domain Immunoglobulin Suppressor of T cell Activation (VISTA/PD-1H) is a B7 family member highly expressed on circulating and intra-tumoral myeloid cells. It is a negative checkpoint inhibitor that inhibits anti-tumor T cell response. In patients, VISTA is associated with poor overall survival in multiple tumor indications and is also a potential mediator of resistance to anti-CTLA-4 and anti-PD1 therapies. Therefore, VISTA is a unique target for cancer immunotherapy. Kineta has developed a fully human monoclonal antibody targeting VISTA, KVA12123, that is currently being evaluated in a Phase 1/2 clinical trial in cancer patients with advanced solid tumors. This trial also includes a combination arm with pembrolizumab. In order to inform which patients may be susceptible to respond to our anti-VISTA antibody, we hypothesized that the best responders should be associated with a high expression of the target in the tumor microenvironment (TME). Therefore, after assay validation of VISTA labelling by immuno-histochemistry, we analyzed a large set of tumor samples and showed that VISTA was highly expressed on tumor infiltrating immune cells. This was particularly true for patients with non-small cell lung cancers, colorectal cancers, head and neck squamous cell carcinomas, hepatocellular carcinomas, melanomas and squamous cell carcinoma of the skin, and cervical cancers as well as ovarian cancers. VISTA expression was detected mostly on CD163 positive macrophages infiltrating the tumor. These macrophages potentially promote immunosuppression present in the TME and contribute to treatment failure with current immune checkpoint inhibitors like anti-PD1/PD-L1 and CTLA-4. While previous studies reported VISTA expression on cancer cells, we were not able to confirm these results. In all tumor tissues tested, only infiltrating immune cells were labelled for VISTA. We have investigated in parallel the expression level of soluble VISTA in the serum collected from cancer patients independent of this clinical trial. Sera were screened for patients with multiple tumor types. Patients of diverse sex and age were compared to healthy donors. After validation of the ELISA assay, we showed that sera derived from cancer patients exhibit high levels of soluble VISTA, and these levels tend to correlate with age. More data are needed to confirm that high levels of soluble VISTA are associated with advanced disease. In the ongoing Phase 1/2 clinical trial, tumor tissues and serum samples will be collected from cancer patients prior to treatment with KVA12123 to inform the possible significance of these biomarkers. This work could help to better understand the response to KVA12123 in relation to the expression level of VISTA in cancer tissues as well as in the blood. Citation Format: Neda Kabi, Chen Katz, Remington Lance, Jessica Cross, Nathan Eyde, Emily Frazier, Kurt Lustig, Yulia Ovechkina, David Peckham, Shaarwari Sridhar, Carla Talbaux, Isabelle Tihista, Mei Xu, Shawn Iadonato, Thierry Guillaudeux. VISTA expression in patients with advanced solid tumors: A potential biomarker in VISTA-101 clinical trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 972.

Qualitative study of Oncology Clinicians' Perceptions of Barriers to Offering Clinical Trials to Underserved Populations.

Cancer clinical trials represent the "gold standard" for advancing novel cancer therapies. Optimizing trial participation is critical to ensuring the generalizability of findings across patients, yet trial enrollment rates, particularly among minority and socioeconomically disadvantaged populations, remain suboptimal. We conducted in-depth interviews with oncologists at a large academic medical center to explore their (1) attitudes and perceived barriers to offering clinical trials to minority and socioeconomically disadvantaged patients, and (2) recommendations for improving the enrollment of minority and socioeconomically disadvantaged patients in cancer clinical trials. Of 23 medical oncologists approached, 17 enrolled (74% response rate; mean age = 47; female = 42%; White = 67%). Content analysis revealed several barriers to enrollment: (1) ethical dilemmas; (2) ambivalence about trial risks and benefits; and (3) concern about patient well-being. Concerns about the legitimacy of informed consent, perceived lack of equipoise, and fear of personal bias influenced clinicians' decisions to recommend trials during treatment discussions. Concerns about creating an imbalance between trial risks and benefits among patients with high-level needs, including patients with literacy, psychiatric, and other socioeconomic vulnerabilities, impacted clinicians' enthusiasm to engage in trial discussions. Clinicians identified patient, provider, and system-level solutions to address challenges, including increasing patient and clinician support as well as involving external personnel to support trial enrollment. Findings reveal multi-level barriers to offering cancer clinical trials to underrepresented patients. Targeted solutions, including system level changes to support clinicians, patient financial support, and implementation of clinical trial navigation programs were recommended to help reduce access barriers and increase enrollment of underrepresented patients into cancer clinical trials.