Participation In Early Phase Clinical Trials Research Articles

A comparative analysis of needs and role of patient navigation among early-phase cancer clinical trial participants and non-participants at a single cancer center.

e23127 Background: Early phase clinical trials (EPCTs) assess the safety and toxicity of novel anticancer agents and represent opportunities for patients (pts) to try novel therapies when standard therapies have become ineffective. However, EPCT participants represent a vulnerable population with high financial toxicity and symptoms related to their cancer and previous treatments. EPCTs often require frequent visits and additional procedures which may be burdensome. Pt navigators perform needs assessments and provide guidance to pts as they move through the health care system. Navigation, which has a high level of acceptance among pts with cancer, can improve time from diagnosis to treatment, decrease pt anxiety, and improve participation of minoritized individuals in clinical trials. We hypothesized that EPCT participants would have higher navigation needs than those of non-EPCT participants with cancer. Methods: Utilizing a needs assessment conducted in person or by telephone, pts with cancer treated at Mount Sinai are assessed for 26 individual and systemic social drivers of health (SDoH) barriers by pt navigators at their trial screening visit. EPCT participants were defined as pts participating in a study in the Early Phase Trials Unit. Descriptive characteristics were assessed for all participants regarding demographic characteristics and SDoH barriers. Welch's T-test was used to compare differences in navigation encounters, SDoH barriers and navigator interventions between the EPCT and non-EPCT pt groups. Results: From February to December 2023, 31 EPCT pts and 3126 non-EPCT pts completed the assessment. Median age was 55.9 and 56.1 years, respectively. Racial and ethnic self-identification included 13% vs. 23% Black pts and 19% vs. 20% Hispanic pts. EPCT pts had a mean 4.87 navigation encounters per pt compared to 1.94 in non-EPCT pts (p < 0.001). Pts in the EPCT group were found to have an average of 24.97 SDoH barriers identified, in contrast to 2.68 in the non-EPCT group (p < 0.001). The most common barriers identified in EPCT pts were institutional, knowledge, and psychosocial; in non-EPCT pts, institutional, treatment adherence, and transportation barriers were most common. Furthermore, based on the identified barriers, EPCT pts required an average of 17.23 interventions, compared to 1.80 among those not in the EPCT group (p < 0.001). Interventions most frequently involved coordination with the primary team and education for pts in both groups. Conclusions: EPCT pts had more navigation encounters, SDoH barriers identified, and resultant interventions than non-EPCT pts. Participants in EPCTs are a vulnerable pt population for whom navigation is particularly warranted. [Table: see text]

Core values of patients with advanced cancer considering participation in an early-phase clinical trial: a qualitative study

ObjectiveThis article identifies the core values that play a role in patients’ decision-making process about participation in early-phase clinical cancer trials.MethodsFace-to-face, semi-structured serial interviews (n = 22) were performed with thirteen patients with advanced cancer recruited in two Dutch specialized cancer centers. In a cyclic qualitative analysis process, open and axial coding of the interviews finally led to an overview of the values that are woven into patients’ common language about cancer and clinical trials.ResultsSix core values were described, namely, acceptance creates room for reconsideration of values, reconciliation with one’s fate, hope, autonomy, body preservation, and altruism. Previously found values in advanced cancer, such as acceptance, hope, autonomy, and altruism, were further qualified. Reconciliation with one’s fate and body preservation were highlighted as new insights for early-phase clinical cancer trial literature.ConclusionsThis article furthers the understanding of core values that play a role in the lives and decision-making of patients with advanced cancer who explore participation in early-phase clinical cancer trials. These values do not necessarily have to be compatible with one another, making tragic choices necessary. Understanding the role of core values can contribute to professional sensitivity regarding what motivates patients’ emotions, thoughts, and decisions and help patients reflect on and give words to their values and preferences. It supports mutual understanding and dialog from which patients can make decisions according to their perspectives on a good life for themselves and their fellows in the context of participation in an early-phase clinical cancer trial.

Supportive care services and goals of care in early phase clinical trials (EP-CTs).

26 Background: EP-CTs investigate novel therapeutic approaches for patients with cancer, but little is known about the use of supportive care services and timing of goals of care (GOC) discussions in EP-CTs. Methods: We conducted a retrospective review of consecutive patients with cancer enrolled on EP-CTs at Massachusetts General Hospital from 2017-2019. We collected information about patients’ demographic/clinical characteristics, use of supportive care services (palliative care [PC], social work [SW], physical therapy [PT], and nutrition), as well as documentation of GOC discussions and code status (before/during EP-CT vs after/never) via chart review. We examined patient characteristics associated with earlier receipt of supportive care services (before/during EP-CT vs after/never) and compared differences in the timing of GOC discussions and code status documented based on the receipt of supportive care services. Results: Among 425 patients enrolled on EP-CTs (median age 63.0; 56.0% female; 97.4% metastatic cancer; 22.1% gastrointestinal cancer), under half received supportive care services before/during trial (PC: 33.2% before/during, 66.8% post/never; SW: 41.9% before/during, 58.1% post/never; PT: 38.4% before/during, 61.6% post/never; and Nutrition: 33.2% before/during, 62.1% post/never). We identified the most common reasons for consulting each of the supportive care services (PC: 82.4% symptom management and 12.4% GOC; SW: 65.3% adjustment to illness and 23.8% referral for resources; PT: 44.8% safety/discharge planning and 24.6% mobility concerns; Nutrition: 73.2% for symptoms of anorexia/poor appetite and 21.5% nutrition assessment). Patients with GI cancer were more likely than those with other cancers to receive PC and SW before/during EP-CT (PC: 29.8% v 18.3%, p =.009; SW: 27.5% v 18.2%, p =.025). Earlier PC was associated with earlier hospice referral (HR = 1.95, p =.014) and shorter survival (HR = 1.54, p <.001). Patients receiving earlier supportive care services were more likely to have GOC discussions documented earlier (PC: 65.2% v 13.0%, p <.001; SW: 41.0% v 22.7%, p <.001; PT: 38.7% v 25.2%, p =.005; Nutrition: 39.1% v 25.0%, p =.002). Patients with earlier PC were more likely to have earlier documented code status (46.8% v 24.3%, p <.001), but not for any other service. Conclusions: In this cohort of patients with advanced cancer, under half received supportive care services before/during their participation in EP-CTs. We found that symptom management represented a common reason for referral to supportive care, highlighting the needs of this population. Patients who received earlier supportive care services were more likely to have earlier documentation of GOC discussions, with those receiving earlier PC having code status documented earlier and also experiencing earlier hospice use and shorter survival. These findings underscore the utility of supportive care services in EP-CTs.

Hospitalizations in solid tumor phase I clinical trial patients: Incidence, pattern and clinical outcomes at an Australian phase I clinical trial unit.

Participation in early-phase clinical trials has become a prominent part of medical oncology patient management. We examined the incidence and pattern of hospitalizations in early-phase clinical trial patients and the associated clinical outcomes. We conducted a retrospective review of 194 patients with solid tumors treated on phase I clinical trials between July 2014 and October 2018 at a phase I trial unit. Unplanned hospitalizations occurring during the study period were characterized and correlated with treatment response and duration of trial participation. Among 194 patients, 104 hospitalizations were recorded involving 62 patients (31%). Nineteen percent of patients were hospitalized for cancer-related complications and 8% for treatment toxicity. No significant correlation was seen between the hospitalization and age, sex, tumor type, or trial drug. Best response to trial therapy was complete response, partial response, stable disease, and progressive disease in 5%, 11%, 37%, and 47% of patients, respectively. Median duration on trial was 86days (range 0-1,412). Twenty-two patients (11%) remained on trial for more than 12 months. Overall, hospitalization did not impact treatment response or trial duration. However, cancer-related hospitalization was associated with significantly lower response (p<0.001) and early patient attrition (p<0.001). Resolution of the hospitalization event was associated with improved response (p=0.002) and longer duration on trial (p<0.001). The treatment related mortality was 0.5% (n=1). Approximately one third of patients required hospitalization, most commonly for cancer-related complications which correlated with poorer clinical outcomes. Hospitalizations related to treatment toxicity were infrequent. A significant proportion of patients derived significant therapeutic benefit. Phase I clinical trials provide a valuable treatment option for patients with cancer.

Involvement of social work services in patients with advanced cancer in early-phase clinical trials (EP-CTs).

28 Background: Early integration of supportive care in patients with advanced cancer has improved quality of life, symptom burden, and survival. Participants in EP-CTs often are highly pre-treated and the demands of participation can exacerbate financial and psychosocial concerns. Integration of social work services can address a broad scope of concerns including behavioral health, psychosocial needs, physical health, and financial concerns. Little data exists regarding the use of social work services in this patient population. Methods: We conducted a retrospective chart review of consecutive patients enrolled in EP-CTs at the MGH Cancer Center during 2017-2019. Information including sociodemographic data, clinical variables, and the use of social work services were captured from the electronic health record. We reviewed documentation in social work notes to determine reason for referral while participating on trial. Results: Of 426 EP-CT participants, 64% ( n = 272) received social work consultations at any time during their cancer course (consultations occurred a median of 23 months [range 0 – 444] following diagnosis). Compared to those who did not receive consultation, patients receiving consultation were younger (median age 60.5 years vs 65 years, p &lt; .001) and more likely to have children (63% vs 46%, p &lt; .001). More than half (59%, n = 159) of consultations occurred prior to EP-CT enrollment, while 14% (n = 39) were during patients’ time on EP-CT. The most common reasons for referral on trial included adjustment to illness (41%), limited patient resources (23%), and home/family support (15%). A quarter of referrals (27%, n = 74) were initiated after patients left the trial (27%, n = 74). There were no significant differences in demographic or clinical variables between those referred on EP-CT versus before or after EP-CT. For those who received social work consultation while on EP-CT, median time from date on treatment to consultation was 18 days (0 – 182 days) while median time on EP-CT was 55 days (2 – 576 days). Patients received a median of 2 visits (1 – 20) while on EP-CT. Physicians and research nurses were most likely to refer patients (31% vs 26%, respectively) while 10% of patients self-referred to social work. Conclusions: Over half of EP-CT participants received social work consultations during their cancer course. Most patients who received consultation on an EP-CT did so for psychosocial support. Future research should focus on determining how best to integrate social work into the care of EP-CT participants.

Long-term overall survival and prognostic score predicting survival: the IMPACT study in precision medicine

BackgroundIn 2007, we initiated IMPACT, a precision medicine program for patients referred for participation in early-phase clinical trials. We assessed the correlation of factors, including genomically matched therapy, with overall survival (OS).Patients and methodsWe performed molecular profiling (Clinical Laboratory Improvement Amendments) (genes ≤ 182) for patients with lethal/refractory advanced cancers referred to the Phase 1 Clinical Trials Program. Matched therapy, if available, was selected on the basis of genomics. Clinical trials varied over time and included investigational drugs against various targets (single agents or combinations). Patients were followed up for up to 10 years.ResultsOf 3487 patients who underwent tumor molecular profiling, 1307 (37.5%) had ≥ 1 alteration and received therapy (matched, 711; unmatched, 596; median age, 57 years; 39% men). Most common tumors were gastrointestinal, gynecologic, breast, melanoma, and lung. Objective response rates were: matched 16.4%, unmatched 5.4% (p < .0001); objective response plus stable disease ≥ 6 months rates were: matched 35.3% and unmatched 20.3%, (p < .001). Respective median progression-free survival: 4.0 and 2.8 months (p < .0001); OS, 9.3 and 7.3 months; 3-year, 15% versus 7%; 10-year, 6% vs. 1% (p < .0001). Independent factors associated with shorter OS (multivariate analysis) were performance status > 1 (p < .001), liver metastases (p < .001), lactate dehydrogenase levels > upper limit of normal (p < .001), PI3K/AKT/mTOR pathway alterations (p < .001), and non-matched therapy (p < .001). The five independent factors predicting shorter OS were used to design a prognostic score.ConclusionsMatched targeted therapy was an independent factor predicting longer OS. A score to predict an individual patient’s risk of death is proposed.Trial registrationClinicalTrials.gov, NCT00851032, date of registration February 25, 2009.

Abstract CT121: Demographics of clinical trial participants for new molecular entity (NME) oncology drugs and biologics approved by FDA CDER in 2015

Abstract Background: In 2015, approximately 810,100 new cancer cases were diagnosed in females in the US. To facilitate the assessment of efficacy and safety of medical products in the diverse populations who might use them after approval, the Food and Drug Administration (FDA) has implemented guidance and regulations to encourage greater participation of women and minorities in clinical trials (CTs). Objectives: To assess demographics in oncology CTs submitted in support of “new drugs” (i.e., New Molecular Entity New Drug Applications (NME NDAs) and original Biologics License Applications (BLAs)) approved by the FDA's Center for Drug Evaluation and Research (CDER) in 2015. Methods: Participation by sex, race, and age (&amp;lt;65 years, ?65 years) and presence of sex-based efficacy and safety analyses were assessed from sponsors’ final clinical study reports for new oncology drugs for adult indications approved in 2015. Sex-based analyses were coded as exploratory or conclusive as previously reported., Results: Fourteen new oncology drugs were approved by CDER in 2015. One BLA and one NDA were excluded from the analysis because they were for pediatric or sex-specific indications. For the 12 remaining drugs, there were 188 trials (phase 1, 2, or 3) that included a total of 17,702 subjects, 48.1% of whom were women. Of the subjects for which race was reported (94.2% of the total), 78.0% were Caucasian, and of those for which age group was reported (75.3% of all subjects), 33.4% were ?65 years of age. Women were 43.1%, 53.2%, and 53.9% of subjects in phase 1, 2, and 3 CTs, respectively. PPR, defined as the Ratio of the Proportion of women in the indicated disease population in the CTs to the Proportion of women in the disease population, was ?0.8 for 11 new drugs and &amp;lt;0.8 for one new drug. Eleven new drugs included both efficacy and safety sex-based analyses, and one new drug included only efficacy sex-based analysis. Conclusions: Relative to their proportion in the disease population, female participation was comparable to (i.e., PPR between 0.8 and 1.2) or greater than men's in late-phase trials for 11 of the 12 oncology drugs examined. Female participation in early-phase CTs was lower than in late-phase CTs; however, late-phase clinical trials are typically where FDA's risk-benefit assessments are made. Citation Format: Hilary Wright, Merina Elahi, Ayomide Igun, Greg Soon, Alice Chen, Anne Pariser, Emmanuel Fadiran. Demographics of clinical trial participants for new molecular entity (NME) oncology drugs and biologics approved by FDA CDER in 2015. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT121.

The changing face of Phase 1 cancer clinical trials

Phase 1 studies in cancer have changed in recent years. Now, with the advent of new, less toxic, targeted agents, more patients may be candidates for new drug studies earlier in the course of their disease. It is to the advantage of the members of the oncology community to know more regarding the details and requirements for participation in early-phase clinical trials so they can advocate for their patients and help them decide when such trials may be an appropriate choice. To examine the work intensity of early phase cancer clinical trials, the authors of this report compared the study requirements of phase 1 and 2 protocols. Five parameters were studied as a surrogate of study complexity-the number of physical examinations, vital sign determinations, electrocardiograms (ECGs), nonpharmacokinetic laboratory tests, and pharmacokinetic (PK) sampling-in the first 4 weeks of protocol in 90 studies (49 phase 1 studies and 41 phase 2 studies). From July 2004 through March 2007, there were 49 phase 1 trials in the phase 1 Program, 9 phase 2 studies that were conducted by physicians appointed in that program, and 32 phase 2 trials with accessible data in the Department of Thoracic/Head & Neck Medical Oncology. In the phase 1 trials versus the phase 2 trials, there were significantly more (P < .05) physical examinations (mean +/- standard error, 3.16 +/- 0.24 vs 2.22 +/- 0.13), vital sign determinations (5.63 +/- 0.61 vs 2.80 +/- 0.26), ECGs (4.36 +/- 1.16 vs 0.80 +/- 0.17), nonpharmacokinetic laboratory tests (18.08 +/- 1.31 vs 10.12 +/- 0.65), and PK sampling (15.14 +/- 1.79 vs 1.02 +/- 0.53). These values also differed significantly (P < .005 for each) when the median values were compared in nonparametric tests. Although both phase 1 and phase 2 trials had substantial study requirements, those for the phase 1 studies were significantly higher. The successful conduct of early-phase clinical trials requires significant research infrastructure.

Expectations of Benefit in Early-Phase Clinical Trials: Implications for Assessing the Adequacy of Informed Consent

Participants in early-phase clinical trials have reported high expectations of benefit from their participation. There is concern that participants misunderstand the trials to which they have consented, which is based on assumptions about what patients mean when responding to questions about likelihood of benefit. Participants were 27 women and 18 men in early-phase oncology trials at 2 academic medical centers in the United States. To determine whether expectations of benefit differ depending on how patients are queried, the authors randomly assigned participants to 1 of 3 interviews corresponding to 3 questions about likelihood of benefit: frequency type, belief type, and vague. In semistructured interviews, participants were queried about how they understood and answered the question. Participants then answered and discussed 1 of the other questions. Expectations of benefit in response to the belief-type question were significantly greater than expectations in response to the frequency-type and vague questions (P=0:02). The most common justifications involved positive attitude (n=27 [60%]) and references to physical health (n=23 [51%]). References to positive attitude were most common among participants with higher (> 70%) expectations (n = 11 [85%]) and least common among those with lower ( < 50%) expectations (n = 3 [27%]). The wording of questions about likelihood of benefit shapes the expectations that patients express. Patients who express high expectations may not do so to communicate understanding but rather to register optimism. Ongoing research will clarify the meaning of high expectations and examine methods for assessing understanding.

Understanding patient expectations in early-phase clinical trials

6543 Background: Participants in early-phase clinical trials have reported high expectations of benefit from their participation. There is concern that participants misunderstand the trials to which they have consented. Such concerns are based on assumptions about what patients mean when they respond to questions about likelihood of benefit. In this study, we explored some of these assumptions. Methods: Participants were 27 women and 18 men in phase 1 or 2 oncology trials and randomized to 1 of 3 interview protocols corresponding to 3 target questions about likelihood of benefit: frequency-type (‘Out of 100 patients who participate in this study, how many do you expect will have their cancer controlled as a result of the experimental therapy?‘); belief-type (‘How confident are you that the experimental therapy will control your cancer?‘); and vague (‘What is the chance that the experimental therapy will control cancer?‘). In semistructured interviews, we queried participants about how they understood and answered the target question. Each participant then answered and discussed one of the other target questions. Results: Participants tended to provide higher expectations in response to the belief-type question (median, 80) than in response to the frequency-type or vague questions (medians, 50) (P=.02). Only 7 (16%) participants said their answers were based on what they were told during the consent process. The most common justifications for responses involved positive attitude (n=27 [60%]) and references to physical health (n=23 [51%]). References to positive attitude were most common among participants with high (&gt;70%) expectations of benefit (n=11 [85%]) and least common among those with low (&lt;50%) expectations of benefit (n=3 [27%]) (P=.04). Conclusions: We identified two factors that should be considered when determining whether high expectations of benefit are signs of misunderstanding. First, participants report different expectations of benefit depending on how the question is asked. Second, the justifications participants give for their answers suggest that many participants use their responses to express hope rather than to describe their understanding of the clinical trial. These findings should inform methods for evaluating the quality of informed consent in early-phase trials. No significant financial relationships to disclose.

A semi-quantitative survey of older adults to assess barriers to participation in early phase clinical trials (EPCTs)

8086 Background: The underrepresentation of older adults in EPCTs severely limits knowledge of drug pharmacology, treatment toxicity and efficacy in this population. We conducted a survey of adults aged 65+ years to describe the prevalence of patient-perceived barriers to participation in EPCTs and to identify factors important to older adults when deciding whether an experimental treatment option is acceptable. Methods: Subjects aged 65+ years with advanced solid tumors who had received prior chemotherapy were recruited from private medical oncology offices affiliated with the University of Colorado Comprehensive Cancer Center and Moffitt Cancer Center clinical research networks. Face-to-face interviews were conducted. Results: To date 219 subjects (median age 74 years (range, 65–89)) have been interviewed. One hundred thirty-six (62%, (95% C.I. 55–69)) subjects endorsed at least 1 barrier to participating in EPCTs. The most commonly reported barriers included difficulty getting to the university to participate in an EPCT (N=73, 33% (95% C.I., 27–40)), concern about being experimented on (N=43, 20% (95% C.I., 15–26)), loss of continuity with their oncologist (N=40, 18% (95% C.I., 13–24)) and adequacy of insurance coverage (N=22, 10% (95% C.I., 6–15)). When deciding whether to participate in an EPCT, 212 (97%) of subjects considered the endorsement of their oncologist to be very important, while only 24 (11%) considered information from the Internet to be very important. Possible benefits of experimental treatment reported to be very important included better symptoms (N=208, 95%) and living longer (N=201, 92%). When considering the possible impact of treatment side effects, subjects considered the following very important: being hospitalized (N=130, 59%), needing more care from family or friends (N=130, 59%), and not being able to care for a spouse or family member (N=112, 51%). Conclusion: The majority of older adults seen in private practices face barriers to participating in an EPCT at a local university. These results have been used to formulate a multifocal, targeted intervention to increase accrual of older adults on EPCTs. No significant financial relationships to disclose.