Therapeutic Clinical Trial Enrollment Research Articles

DISP-05. SUPERVISED MACHINE LEARNING PREDICTION OF THERAPEUTIC CLINICAL TRIAL ENROLLMENT FOR MINORITY PATIENTS AND WOMEN IN NEURO-ONCOLOGY

Abstract BACKGROUND Despite changes in national policy, women and minority patients remain under-accrued in glioma clinical trials. Supervised machine learning may serve as a novel approach to understanding which variables and their complex interplay most influence enrollment for underrepresented patients. We aimed to design and externally validate machine learning models to predict therapeutic clinical trial enrollment for a) all patients, b) women, and c) NIH-designated minority patients with low- and high-grade glioma. METHODS In a 20-year retrospective cohort of 1042 adult patients with low- and high-grade glioma, boosted neural network (BNN) models for the whole, women, and minority cohorts were used to analyze the combined effects of demographic, socioeconomic, and oncologic variables on clinical trial enrollment. These models were validated using an external cohort (n=103). RESULTS In the development cohort (445 [42.7%] women; 151 [14.5%] minorities; median age, 51.5 [interquartile range: 39.4-62.5] years), 350 patients (33.6%) enrolled in a therapeutic clinical trial. The whole cohort BNN (AUC: 0.827, misclassification rate (MR): 0.175), the women cohort BNN (AUC: 0.895, MR: 0.125), and the minority cohort BNN (AUC: 0.983, MR: 0.053) models accurately predicted trial enrollment on external validation. For the whole cohort and women models, several demographic (race, ethnicity, minority status, sex), socioeconomic (insurance, employment status), and oncologic variables (seizure, chemotherapy, KPS, WHO grade, tumor lobe) were equally influential (Main effect (ME): 1.000, Total effect (TE): 1.000) on enrollment. For the minority model, socioeconomic variables including insurance status (ME: 0.089, TE: 0.417) and occupation classification (ME: 0.087, TE: 0.381) drove enrollment. CONCLUSION We designed and externally validated the first machine learning model for predicting therapeutic clinical trial enrollment for patients with diffuse glioma. Model features driving trial enrollment varied for underrepresented patients. These results may help prioritize personalized patient-specific initiatives to address barriers to equitable patient accrual.

Predicting therapeutic clinical trial enrollment for underrepresented patients in neuro-oncology using supervised machine learning.

1614 Background: Despite the unique ability of machine learning (ML) techniques to uncover complex interactive effects in datasets, studies exploring predictors of clinical trial enrollment have largely used standard statistical methods to discern associations. Furthermore, there have been limited applications of ML to close existing disparities in clinical trial enrollment of underrepresented patients in neuro-oncology. This study aims to use supervised machine learning to define and validate primary contributors of therapeutic clinical trial enrollment for a) all patients, b) women and c) NIH-designated minority patients with low- and high-grade glioma. Methods: Adult glioma patients who received care from the UCSF Brain Tumor Center between 1997- 2017 were identified in a prospective registry. Bootstrap forest (BF) and Recursive Partitioning (RP) models were created by randomly dividing patients in a 70/30 split into development (DEV) and validation (VAL) cohorts among all patients, women, and NIH-designated minority patients, separately. Model performance was assessed using the area under the curve (AUC) in the DEV and VAL cohorts. Results: Among 1042 patients, 350 patients (33.6%) enrolled in a therapeutic clinical trial. There were 445 women (42.7%), of which 144 (32.4%) enrolled, and 141 minority patients (13.5%), of which 39 (27.7%) enrolled. For all patients, in order of decreasing influence, the BF model selected median neighborhood household income, age, neighborhood poverty level, distance from hospital, tumor location, tumor volume, treatment with chemotherapy, occupation, KPS, insurance status, employment status, seizure at presentation, and volumetric extent of resection (EOR) to predict trial enrollment (DEV AUC: 0.984; VAL AUC: 0.746). For women, the BF model selected distance from hospital, age, household income, neighborhood poverty level, tumor location, treatment with chemotherapy, and KPS for trial prediction (DEV AUC: 0.972; VAL AUC: 0.746), whereas for minority patients, the BF model selected neighborhood poverty level, age, occupation, distance from hospital, tumor volume, insurance status, employment status, and EOR to predict trial enrollment (DEV AUC: 0.9830; VAL AUC: 0.769). The RP model for women designated those with non-White race as less likely to enroll (DEV AUC: 0.735; VAL AUC: 0.665) while the RP model for minority patients characterized those who preferred a non-English language or who were divorced or widowed as less likely to enroll (DEV AUC: 0.775; VAL AUC: 0.601). Conclusions: Supervised machine learning models achieved similar predictive performance among patient subgroups, while uncovering interactions between gender identity, minority status, and sociodemographic variables. These findings can guide targeted recruiting efforts to advance equitable trial enrollment for women and minorities.

Abstract 1006: Revitalizing the accrual of women and minorities: Unique drivers of therapeutic clinical trial enrollment for underrepresented patients with diffuse glioma

Abstract Introduction: Despite the enactment of the 1993 NIH Revitalization Act to improve accrual of women and minorities in clinical trials, these groups remain underrepresented. This study aims to uncover drivers of therapeutic clinical trial enrollment that are unique to women and minority patients with low- and high-grade glioma. Methods: Adult glioma patients who received care from the UCSF Brain Tumor Center between 1997-2017 were identified in a prospective registry. Dividing the cohort into subgroups by gender and NIH-designated minority status, factors associated with therapeutic clinical trial enrollment on univariate logistic regression (p<0.2) were selected for multivariate logistic regression. Results: There were 351 trial participants (41% women, 12% minority) and 627 non-trial participants (44% women, 17% minority). Among women only, seizure at presentation (OR 2.10, p=0.008) was associated with increased odds of trial enrollment. In contrast, among men only, higher median household income (OR 1.09 per $10,000 increase, p=0.006), higher WHO tumor grade (OR 1.89, p=0.045), and occupational status according to the International Standard Classification of Occupations [professionals (e.g., physicians) vs managers (e.g., supervisory positions), OR 2.87, p=0.043] were associated with increased odds of trial enrollment. Among both women and men, lack of insurance (women: OR 0.49, p=0.02; men: OR 0.55, p=0.031) and no treatment with chemotherapy (women: OR 0.18, p=0.001; men: OR 0.34, p=0.002) were associated with decreased odds of clinical trial enrollment, whereas higher KPS (women: 90 vs <80, OR 3.16, p=0.003; men: 90 vs <80, OR 3.15, p=0.002) was associated with increased odds of trial enrollment. Among NIH-designated minority patients, older age (OR 0.66 per 10-year increase, p=0.033) and non-English preferred language (OR: 0.30, p=0.035) were associated with decreased odds of trial enrollment on univariate analysis, but not on multivariate analysis. Among non-minority patients, lack of insurance (OR 0.58, p=0.008) and no chemotherapy treatment (OR 0.25, p<0.001) were associated with decreased odds of trial enrollment, whereas seizure at presentation (OR 1.80, p=0.001), higher neighborhood household income (OR 1.07 per $10,000 increase, p=0.004), higher WHO grade (4 vs 2-3, OR 1.86, p=0.015), higher KPS (90 vs <80, OR 3.21, p<0.0001), and lower extent of tumor resection (80-89% vs 100%, OR 2.16, p=0.047) were associated with increased odds of trial enrollment. Conclusion: Drivers of trial enrollment differed for women and minority patients with glioma. Non-English-speaking minority patients may face additional barriers to trial enrollment requiring targeted interventions. Our findings can revitalize and tailor efforts to recruit women and minority patients to therapeutic clinical trials in neuro-oncology. Citation Format: Mulki Mehari, Gayathri Warrier, Sheantel Reihl, Abraham Dada, Aymen Kabir, Mikias Negussie, Cesar Nava Gonzales, Ugonma Chukwueke, Alyx Porter, Shawn Hervey-Jumper. Revitalizing the accrual of women and minorities: Unique drivers of therapeutic clinical trial enrollment for underrepresented patients with diffuse glioma [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 1006.

Critical Decisions: A mixed-methods study investigating decision-making and disparities among diverse gynecologic cancer patients considering therapeutic clinical trial enrollment (014)

Objectives: Disparities in clinical trial enrollment are extensive and persistent. From 1994-2013, 83% of GOG trial participants were White, despite the similar willingness of participation among diverse groups. This limits study generalizability and marginalized patients’ access to novel therapeutics. This mixed-method study at an academic institution in a rural state included groups underrepresented in clinical trials, including American Indian and Hispanic, sexual and gender minority, and less well-educated patients. Institutional enrollment exceeds national numbers and reflects broader state demographics, allowing investigation of patients’ decision-making regarding clinical trial participation. Methods: We conducted surveys and in-depth qualitative interviews with 27 gynecologic cancer patients eligible for therapeutic clinical trials. Their gynecologic oncologists completed parallel surveys. Two investigators completed an iterative analysis of interviews, eliciting themes pertinent to decision-making, patient-provider relationships, and illness experiences. Surveys addressed shared decision-making, decisional conflict, and patient-centered care. We compared patient and provider survey data for participants who enrolled and those who did not, using Fisher’s exact tests. Conclusions: Concerns regarding social support and coping, exacerbated by experienced distress, unmet needs, and vulnerability, shape clinical trial enrollment in gynecologic cancer. Discussions of clinical trial disparities often focus on patient education, yet participants in this study expressed receiving sufficient information to make shared decisions with their providers. Those who remained unenrolled reported more apprehension regarding cancer diagnosis and treatment, making the additional uncertainty of clinical trials unmanageable. Reasons posited for such differences include coping styles, degree of social support, and perceptions that clinical trials may result in additional vulnerabilities for patients and their families. Therefore, for clinical trial participation to be feasible for vulnerable patients, interventions must provide significant social/economic support and recognize and manage patient distress related to isolation, treatment options, and coping. The next step includes developing tools to support historically marginalized patients, many of whom have experienced minority stress, to mitigate the uncertainty of clinical trial enrollment. Objectives: Disparities in clinical trial enrollment are extensive and persistent. From 1994-2013, 83% of GOG trial participants were White, despite the similar willingness of participation among diverse groups. This limits study generalizability and marginalized patients’ access to novel therapeutics. This mixed-method study at an academic institution in a rural state included groups underrepresented in clinical trials, including American Indian and Hispanic, sexual and gender minority, and less well-educated patients. Institutional enrollment exceeds national numbers and reflects broader state demographics, allowing investigation of patients’ decision-making regarding clinical trial participation. Methods: We conducted surveys and in-depth qualitative interviews with 27 gynecologic cancer patients eligible for therapeutic clinical trials. Their gynecologic oncologists completed parallel surveys. Two investigators completed an iterative analysis of interviews, eliciting themes pertinent to decision-making, patient-provider relationships, and illness experiences. Surveys addressed shared decision-making, decisional conflict, and patient-centered care. We compared patient and provider survey data for participants who enrolled and those who did not, using Fisher’s exact tests. Conclusions: Concerns regarding social support and coping, exacerbated by experienced distress, unmet needs, and vulnerability, shape clinical trial enrollment in gynecologic cancer. Discussions of clinical trial disparities often focus on patient education, yet participants in this study expressed receiving sufficient information to make shared decisions with their providers. Those who remained unenrolled reported more apprehension regarding cancer diagnosis and treatment, making the additional uncertainty of clinical trials unmanageable. Reasons posited for such differences include coping styles, degree of social support, and perceptions that clinical trials may result in additional vulnerabilities for patients and their families. Therefore, for clinical trial participation to be feasible for vulnerable patients, interventions must provide significant social/economic support and recognize and manage patient distress related to isolation, treatment options, and coping. The next step includes developing tools to support historically marginalized patients, many of whom have experienced minority stress, to mitigate the uncertainty of clinical trial enrollment.

The Care of Children With Cancer During the COVID-19 Pandemic.

The COVID-19 pandemic has considerably changed health services for children with cancer worldwide by creating barriers throughout the care continuum. Reports available at this time suggest that asymptomatic and mild upper and lower respiratory tract syndromes are the most common presentation of COVID-19 in children with cancer. Nonetheless, severe cases of COVID-19 and deaths secondary to the infection have been reported. In addition to the direct effects of the severe acute respiratory syndrome coronavirus 2, children with cancer have suffered from the collateral consequences of the pandemic, including decreased access to diagnosis and cancer-directed therapy. The COVID-19 pandemic has presented unprecedented challenges to safe and effective care of children with cancer, including their enrollment in therapeutic clinical trials. Data from the Children's Oncology Group and Cancer Research U.K. Clinical Trials Unit show variability in the enrollment of children with cancer in clinical trials during the COVID-19 pandemic. However, the overall effects on outcomes for children with cancer undergoing care during the pandemic remain largely unknown. In this article, we review the current knowledge about the direct and collateral effects of the COVID-19 pandemic, including on clinical trial enrollment and operations.

Utilization of a multisite financial reimbursement program to promote racial/ethnic diversity and inclusion in therapeutic cancer clinical trials: The iMPACT Study.

85 Background: A lack of racial/ethnic diversity among cancer therapeutic clinical trial (TCT) participants remains a critical problem. The significance of costs, both direct and indirect, associated with cancer TCT participation are increasingly understood. Here, we report findings observed in the IMproving Patient Access to Cancer clinical Trials (IMPACT) study, a pilot feasibility study investigating the feasibility and efficacy of offering a financial reimbursement program (FRP) during cancer TCT discussion with or without additional outreach in improving enrollment and diversity. Methods: Participants for this study were recruited at two Comprehensive Cancer Centers (CCCs) from April to September 2019. Patients were randomized 1:1 to receive a brochure about a FRP at time of consent for a TCT or receive brochure and outreach through a scripted follow-up phone call regarding the FRP. Results: No difference in TCT enrollment was observed between study arms. Among 170 patients approached to participate, 132 (78%) provided consent. The participant mean age was 57 years old (std dev = 14 years). Among participants 57% were male and 49% were white. The remaining major racial/ethnic groups were Black (5%) Asian (13%) and Hispanic (26%). The proportion of non-whites was greater among IMPACT study (43%) compared to CCC TCT (28%) participants. Among FRP participants, 24% reported a household income < $25,000 and 14% from $25,001 to $56,000. Conclusions: This study observed that offering an FRP as part of TCT discussion is feasible and effective at CCCs. An outreach phone call is not required in order to influence enrollment in TCT. FRP recipients are racially/ethnically diverse and low socioeconomic status.

Abstract A045: Increasing minority accrual in breast cancer clinical trials through a multidisciplinary approach

Abstract Breast cancer is the most common cancer in Hispanic/Latina women in the United States (U.S.). Yet, therapeutic cancer clinical trial enrollment among Hispanic/Latina women remains low. Barriers to participation are varied and multifactorial. Health provider and system level barriers at cancer centers in the U.S. include language and cultural discordant communication among providers and patients, transportation (to/from study site), and provider discomfort and skepticism in patient adherence. Recent studies have found that Hispanic/Latina women do not exhibit major concerns related to trust and if adequately informed and invited to participate in therapeutic trials, they are likely to do so. A qualitative study was conducted to understand the factors that influence participation in breast cancer clinical trials among Hispanic/Latina breast cancer patients. We conducted 10 semi-structured in-depth interviews in Spanish with women currently receiving radiation treatment, to identify patient level barriers and facilitators for clinical trial participation. Participants were recruited from the University of California (UC) San Diego Moores Cancer Center and UC Health System-affiliated radiation oncology center. Data were analyzed using a conventional content analysis framework to describe the personal and emotional reactions of Hispanic/Latina women who have been breast cancer patients. The main strength of this approach is to allow ideas and beliefs to emerge from the data to provide new insights that capture key thoughts and values of our participants and their treatment experiences and preferences. The analysis and interpretation were specifically conducted in Spanish to maintain language and cultural concordance with our participants. The final analyses were translated from Spanish to English by bilingual and bicultural study investigators. Preliminary findings reveal that Hispanic/Latina women are more likely to participate in breast cancer clinical trials if study information is delivered in-person, the study location is geographically close to their home, they receive appointment reminders by phone or text, study appointment duration is short, the study uses less invasive medications/treatments, and study personnel deliver a supportive experience (i.e. respectful and professional) during enrollment and throughout the study. Barriers to participation include language concordance, a lack of information about cancer clinical trials, fear of potential risks, a competing focus between their current cancer treatment and clinical trial activity, and a lack of time. Our final in-depth analyses will present detailed thematic results, interpretation, and practice application. These outcomes may guide efforts to improve racial/ethnic minority therapeutic clinical trials enrollment, retention, and related outreach among Hispanic/Latina patients accessing care at comprehensive cancer centers. Citation Format: Valesca Largaespada, Samantha Hurst, Savannah M Bradley, Myriam I Acosta, Jonathan Unkart, Sarah Blair, Jesse Nodora. Increasing minority accrual in breast cancer clinical trials through a multidisciplinary approach [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A045.

Abstract A056: A study of race and socioeconomic status impacting therapeutic clinical trial enrollment in adult gliomas patients

Abstract Introduction: Under-enrollment in clinical trials significantly limits valid analyses of clinical interventions and generalizability of findings. It can also result in premature study termination, with estimates of 22% to 50% of clinical trials being terminated due to poor accrual. Currently, there are limited reports addressing the influence of race, ethnicity and socioeconomic status on clinical trial enrollment in patients with adult glioma. The goal of this study was to determine if race and socioeconomic status impacts clinical trial participation for glioma patients. Methods: A search within the UCSF Tumor Board Registry identified 852 adult patients discussed over a 2-year period. This cohort was analyzed to determine the rate of therapeutic clinical trial consideration, tumor board recommendation, and study enrollment based on clinical reports available through the electronic medical record. Results: At the time of initial diagnosis, 30.7% and 18.0% of glioma patients were recommended and enrolled in a therapeutic clinical trial, respectively. At the time of recurrence, 38.7% and 25.3% of patient were recommended and enrolled in a clinical trial, respectively. Nineteen percent of the study population belonged to a NIH designated underrepresented minority group, with Asian/Pacific Islander patients comprising 10.3% of the total patient cohort. Percentage of patients who enrolled in a clinical trial was comparable between subgroups. On univariate analysis, only in-state location, distance to the hospital, and WHO grade were associated with consideration, recommendation, and enrollment at initial diagnosis and recurrence. Minority status, insurance type, median household income, and percent below poverty line based on county of residence were not associated with clinical trial recommendation or enrollment. Conclusion: Race and socioeconomic status did not impact clinical trial consideration, tumor board recommendation, or study enrollment. Our results do not support the premise that provider decisions are impacted by biases based on minority or socioeconomic status. Citation Format: Sheantel J Reihl, Ramin A Morshed, Sofia Kakaizada, Eric Zhang, Jacob S Young, Jennifer Clarke, Nicholas Butowski, Jennie Taylor, Nancy Ann Bush, Manish K Aghi, Mitchel S Berger, Susan Chang, Shawn L Hervey-Jumper. A study of race and socioeconomic status impacting therapeutic clinical trial enrollment in adult gliomas patients [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A056.

The influence of race and socioeconomic status on therapeutic clinical trial screening and enrollment.

Under-enrollment in clinical trials significantly limits valid analyses of clinical interventions and generalizability of findings. Often it results in premature study termination, with estimates of 22% to 50% of clinical trials terminated due to poor accrual. Currently, there are limited reports addressing the influence of race/ethnicity and socioeconomic status on clinical trial enrollment in adult glioma patients. The goal of this study was to test the hypothesis that race and socioeconomic status negatively impact therapeutic clinical trial enrollment. 988 adult patients were identified from the UCSF Tumor Board Registry and analyzed to determine the rate of therapeutic clinical trial screening and study enrollment. At initial diagnosis, 43.6% and 17.5% of glioma patients were screened and enrolled in a therapeutic clinical trial, respectively. At recurrence, 49.8% and 26.3% of patients were screened and enrolled in a clinical trial, respectively. Thirty-three percent of the study population belonged to a NIH-designated underrepresented minority group; Asian/Pacific-Islander comprised 19.6% of the overall cohort. On univariate analysis, only in-state location, distance to the hospital, and WHO grade were associated with enrollment at initial diagnosis and recurrence. Minority status, insurance type, median household income, and percent below poverty were not associated with clinical trial enrollment. Minority and socioeconomic status did not impact adult glioma clinical trial enrollment. Proximity to the tertiary care cancer center may be an important consideration for minority patients. Patient screening should be carefully considered in order to avoid bias based on minority and socioeconomic status.

Communication Regarding Therapeutic Clinical Trial Enrollment Between Oncologists and Adolescents and Young Adults with Cancer.

Adolescent and young adult (AYA) cancer patients enroll in therapeutic clinical trials at low rates. Prior study has focused on trial availability; this research attempts to elucidate the role of communication in individual decision-making. We surveyed 193 AYA patients and reviewed medical records of informed consent discussions. Twenty percent (38/193) of patients were offered trials, 58% (22/38) enrolled. Many were unable to correctly identify whether they were offered trials or enrolled, including 27% (6/22) of patients on clinical trials who believed that they were not. Efforts to improve communication have potential to enhance informed decision-making in this vulnerable population.

Video intervention increases participation of black breast cancer patients in therapeutic trials

There is a striking racial and ethnic disparity in incidence and mortality of cancer yet minorities remain markedly underrepresented in clinical trials. This pilot study set out to determine the impact of a 15-min culturally tailored educational video on three outcomes relating to clinical trials: likely participation, attitudes (assessed based on six barriers), and actual enrollment. Breast cancer patients with Stage I-III, if diagnosed within previous 6 months, or metastatic disease who self-identified as black or African American were invited to participate. The primary outcome measure was the decision to participate in a therapeutic clinical trial after the intervention. Patients’ intention to enroll on a therapeutic clinical trial and the change in attitudes toward clinical trials were measured by the previously developed Attitudes and Intention to Enroll in Therapeutic Clinical Trials (AIET) questionnaire. Of the 200 patients that participated, 39 (19.5%) patients signed consent to participate in a therapeutic clinical trial; 27 (13.5%) patients enrolled, resulting in a 7.5% increase from our baseline comparison of 6% clinical trial enrollment rate in black cancer patients (p < .001). Pre-test versus post-test assessment demonstrated the proportion of patients expressing likelihood to enroll in a therapeutic trial following the intervention increased by 14% (p < .001). Among 31 AIET items, 25 (81%) showed statistically significant and positive change post-intervention. The findings suggest the promising utility of a culturally tailored video intervention for improving black patients’ attitudes regarding clinical trial participation and resultant enrollment. Future efforts should continue to target facilitators of population-specific recruitment, enrollment, and retention in therapeutic and non-therapeutic clinical trials.

No improvement in clinical trial enrollment for adolescents and young adults with cancer at a children's hospital.

We have previously published data from 2001 to 2006 showing that adolescent and young adult (AYA) oncology patients have significantly lower therapeutic clinical trial enrollment rates than younger patients. Our objective was to determine if the enrollment of AYA patients on therapeutic studies at the same institution has improved in recent years with the greater focus on this population locally and nationally. We retrospectively analyzed cancer registry data at the Children's Hospital of Pittsburgh (CHP) for all new oncologic diagnoses between January 2010 and December 2014. These data included age, gender, diagnosis, race and whether the patient was enrolled on an open treatment study. Univariate analyses were carried out to compare demographic data between AYA patients (aged 15-22) who enrolled on study and those who did not. Eight hundred sixty-five new oncology patients were seen at CHP during this time, 23% of whom were 15 years or older; 33% of all patients were treated on a clinical trial, including 34% of younger patients and 24% of older patients (P = 0.0017). The differences between these rates and those from prior years in both age groups (38% and 27%, respectively) were not statistically significant (P = 0.15, 0.53). The most common reason for the low enrollment rates was again the lack of an open therapeutic trial. Despite initiatives at CHP and on the national level to enroll more AYA patients on clinical trials, our most recent data show no improvement. This is a potentially remediable factor that needs to continue to be prioritized nationally.

Clinical research participation among adolescent and young adults at an NCI-designated Comprehensive Cancer Center and affiliated pediatric hospital.

Minimal clinical trial participation among adolescents and young adults (AYAs) with cancer limits scientific progress and ultimately their clinical care and outcomes. These analyses examine the current state of AYA clinical research participation at a Midwestern comprehensive cancer center and affiliated pediatric hospital to advise program development and increase availability of trials and AYA participation. Enrollment is examined across all diagnoses, the entire AYA age spectrum (15-39), and both cancer therapeutic and supportive care protocols. his study was a retrospective review of electronic medical records via existing databases and registries for all AYAs. Data were collected for AYAs seen by an oncologist at the adult outpatient cancer center or at the pediatric hospital between the years 2010 and 2014. Descriptive statistics and logistic regression analyses were conducted to characterize this sample. In the pediatric setting, 42.3% of AYAs were enrolled in a study compared to 11.2% in the adult setting. Regression analyses in the pediatric setting revealed that AYAs with private insurance or Caucasian race were more likely to participate. Within the adult setting, ethnicity, race, insurance, and diagnosis were associated with study participation; 54.8% of study enrollments were for cancer therapeutic and 43.4% for supportive care studies. These results are comparable to previously published data and support the need for new local and national AYA initiatives to increase the availability of and enrollment in therapeutic clinical trials. The same is true for supportive care studies which play a crucial role in improving quality of life.

Enrollment in Clinical Cancer Trials

Clinical trials contribute to the establishment of the best therapy for children with cancer. This study looks at rates of enrollment in therapeutic clinical trials over a 2-year period in New Zealand and examines the reasons for nonenrollment. All new diagnoses of cancer in children aged 16 or younger over the period of 1 January, 2009 to 31 December, 2010 were identified through the New Zealand Child Cancer Registry. Clinical trial enrollment status was identified from the medical records. For those not enrolled, the reason for nonenrollment was ascertained. A total of 28% of children diagnosed with cancer who received chemotherapy with curative intent in this time period were enrolled on clinical trials. The 2 most common reasons for nonenrollment in this study were that no study was open locally in which to enroll children (27%) or that previously open-clinical trials were closed to accrual at the time of the child's diagnosis (20%). In New Zealand, enrollment rates on clinical trials for children with cancer are lower than expected.

Improving enrollment in clinical trials for adolescents with cancer.

Overall cancer cure rates have risen over the last 30 years. Adolescent and young adult (AYA) oncology patients aged 15 to 39 have not shared in these successes as an age group, including those who fall into the younger age group of 15 to 19 years. The reasons for this deficit in survival improvement are manifold, but research has shown that an important factor is decreased enrollment in therapeutic clinical trials in this population versus younger patients. The paucity of adolescents treated in clinical trials is itself the result of several elements of the health care landscape in the United States. On the local level, these factors include referral patterns and facilities available; on the national level, related factors include the number of clinical trials available for this age group and health care provider education in the care of these patients. We examine the data available that have contributed to this deficit in the United States and offer broad strategies to address these shortcomings with the goal of improving outcomes in this underserved population.

Impact of routine tumor genotyping on enrollment in targeted therapy trials for metastatic breast cancer (MBC): 4-year review.

145 Background: Major barriers to enrollment in therapeutic clinical trials (&lt;5% in United States) include low response rate in phase I/II trials and low enthusiasm among oncologists. Stratified clinical trial enrollment based on molecular profiling of tumors represents a potential paradigm shift in drug development. Here we assess the clinical utility of tumor genotyping for identification of oncogenic driver mutations and enrollment in therapeutic clinical trials for patients with metastatic breast cancer (MBC). Methods: A robust, high-throughput tumor genotyping assay (Snapshot), was developed at our institution to assess for presence of potentially actionable oncogenic driver mutations (15 genes, 130 mutations) using DNA derived from formalin-fixed, paraffin-embedded (FFPE) tissue. The tumor genotyping assay was ordered by oncologists in clinic for patients with MBC. Relevant clinical information was gathered from chart reviews. Descriptive statistics were used for analysis. Results: From 2009-2012, 347 breast tumors were prospectively genotyped in the study population (median age = 50, range 27-90). The common oncogenic mutations were seen in all breast cancer subtypes. PIK3CA mutation (23.3%) was the most common mutation detected overall, albeit at varying frequency in tumor subtypes: HR+ (29.1%, N= 210), HER-2+ (21.5%, N = 65), TN (8.3%, N = 72). Unanticipated mutations in KRAS, BRAF, IDH, and HER-2 were also discovered. Clinical genotyping helped identify breast origin for carcinomas of unknown primary and revealed changes in mutation profile in metastatic tumors from primary tumors. Enrollment in clinical trials for MBC almost quadrupled from 2005-2008 to 2009-2012, with approximately one-third of patients undergoing tumor genotype testing enrolling in clinical trials, particularly phase-I genotype-directed targeted therapy, such as PI3K inhibitor, Akt inhibitor, and PI3K/MEK inhibitor combination. Conclusions: Routine tumor genotyping can be successfully incorporated into clinical practice to significantly enhance therapeutic clinical trial enrollment and potentially accelerate development of genotype-directed targeted therapies for MBC.

Impact of routine tumor genotyping on enrollment in targeted therapy trials for metastatic breast cancer (MBC): 4-year review.

533 Background: Major barriers to enrollment in therapeutic clinical trials (&lt;5% in United States) include low response rate in phase 1/2 trials and low enthusiasm among oncologists. Stratified clinical trial enrollment based on molecular profiling of tumors represents a potential paradigm shift in drug development. Here we assess the clinical utility of tumor genotyping for identification of oncogenic driver mutations and enrollment in therapeutic clinical trials for patients with MBC. Methods: A robust, high-throughput tumor genotyping assay (Snapshot), was developed at our institution to assess for presence of potentially actionable oncogenic driver mutations (15 genes, 130 mutations) using DNA derived from formalin-fixed, paraffin-embedded (FFPE) tissue. The tumor genotyping assay was ordered by oncologists in clinic for patients with MBC. Relevant clinical information was gathered from chart reviews. Descriptive statistics were used for analysis. Results: From 2009-2012, 347 breast tumors were prospectively genotyped in the study population (median age = 50, range 27-90). PIK3CA mutation (23.3%) was the most common mutation detected overall, albeit at varying frequency in tumor subtypes: HR+ (29.1%, N= 210), HER-2+ (21.5%, N = 65), TN (8.3%, N = 72). Unanticipated mutations in KRAS, BRAF, IDH, and HER-2 were also discovered. Clinical genotyping helped identify breast origin for carcinomas of unknown primary and revealed changes in mutation profile in metastatic tumors from primary tumors. Enrollment in clinical trials for MBC almost quadrupled from 2005-2008 to 2009-2012, with 35.5% of patients undergoing tumor genotype testing enrolling in trials, particularly phase-1 genotype-directed targeted therapy, such as PI3K inhibitors, Akt inhibitors, and combined PI3K/MEK inhibitors. Conclusions: Routine tumor genotyping can be successfully incorporated into clinical practice to significantly enhance therapeutic clinical trial enrollment and potentially accelerate development of genotype-directed targeted therapies for MBC.

Stepwise examination of prostate clinical trials participation to reduce accrual barriers.

157 Background: Adequate and representative enrollment in therapeutic clinical trials is important to an NCI cancer center. Clinical trial participation is a string of 6 sequential patient and physician decisions beginning with an available therapeutic trial to enrollment in the trial. Opportunities for participation may be lost at any one of these steps. The objective of this study was to calculate transitional probabilities that measure patient, especially minority patient, accrual to clinical trials at the Sidney Kimmel Comprehensive Cancer Center and to describe the barriers for those dropping out at each step. Methods: Records for “first visit” medical oncology patients seen by three SKCCC physicians from January to April 2010 were abstracted. Prostate cancer case reports from the hospital cancer registry and a medical record review provided age, race, Hispanic ethnicity, place of residence, tumor characteristics, and prior treatment history. At each transition step, we calculated the proportion of patients who remained enrollable. Results: Overall, prostate cancer clinical trial participation was 17% (16/94). Minority accrual was similar to Caucasian accrual at 19% and 17% , respectively. Retention at each step of trial participation was highest for “discussed” (98%), “enrolled” (94%), “eligibility” for available trials (79%), and “consented” (71%). Two bottlenecks were qualitatively identified: “trial availability” (65%) and “patient interest” (51%). Forty-two percent of those for whom there was no trial available were older than 70 years and 33% were patients with rising PSA after local therapy and hormone-naïve. The “patient interest” step was shaped primarily by disinterest due to distance to SKCCC (83%). Conclusions: For prostate cancer patients, recruitment to medical oncology clinical trials is robust. Minority patients however are only 17% of all patients seen and half drop out when no trial is available and half of those remaining judged distance to be a problem (hence, no interest). This study approach has clarified which factors are likely to be barriers to participation and is likely useful to making adjustments that can reduce identified barriers by adding to trial portfolio as an example.

Improved clinical trial enrollment in adolescent and young adult (AYA) oncology patients after the establishment of an AYA oncology program uniting pediatric and medical oncology divisions

Since 1975, there has been a dramatic increase in the survival rates of pediatric and older cancer patients, but adolescent and young adult (AYA) patients ages 15 to 40 years have not had a similar improvement. Data indicate a direct correlation between increased cure rates and clinical trial enrollment. The authors previously published data indicating inferior clinical trial enrollment when AYA patients were treated at an adult oncology center versus a pediatric oncology center. To address this deficit, a joint pediatric and adult AYA Oncology Program was established in July 2006 with the primary objective of improving outcomes by increasing therapeutic clinical trial enrollment in this population. Patients who were referred to that program from July 2006 through June 2010 were examined retrospectively to establish whether clinical trial enrollment increased compared with historic controls. Fifty-seven patients were referred to the program from 2006 to 2010 (range, 12-16 new patients per year). Eight patients were referred for consultation only and were not treated at the University of Pittsburgh Cancer Institute or Children's Hospital of Pittsburgh. Five of 22 patients (23%) who received treatment at the pediatric cancer center were enrolled onto a clinical trial, whereas 9 of 27 patients (33%) patients who received treatment at the adult cancer center were enrolled. There was superior trial participation compared with the previous 3 years for those shared AYA patients who were treated at the adult center (P < .001). Data from this study demonstrated that establishing a unified AYA oncology program can lead to improved clinical trial enrollment for patients who are treated at medical oncology centers.

P1-11-06: Barriers to Enrollment in Cancer Therapeutic Clinical Trials: A Comprehensive Cancer Center Experience.

Abstract PURPOSE: Well-conducted cancer therapeutic clinical trials are essential for improving patient outcomes. Unfortunately, less than 5% of new cancer patients participate in clinical trials on average nationwide. Failure to recruit eligible patients represents a major impediment to the success of clinical trials. Barriers to patient accrual in cancer clinical trials must be identified and overcome to increase patient participation. MATERIALS AND METHODS: A retrospective analysis of 418 patients with a diagnosis of breast cancer seen at City of Hope Medical Center in 2009 was performed. Along with descriptive analysis of patient demographic data, logistic regression analyses were performed to evaluate predictors of enrollment. RESULTS: Of the 418 new breast cancer patients in 2009, we determined that 138 (33%) were eligible for available therapeutic clinical trials at City of Hope. At the initial visits, physicians did not consider clinical trials in 32% (44/138) of these patients. Of the 138 eligible patients, 58% (80/138) of patients participated in clinical trials. The remainder (58/138, 42%) either declined trial participation despite meeting eligibility criteria (14/58, 24%), or were not considered for clinical trials by their respective physician (44/58, 76%). By logistic regression analysis, patients with Stages II and III disease were significantly more likely to enroll in clinical trials compared to those with stage 0 or I (OR=2.89, 95% CI, 1.17−7.12, P = .02; OR=9.17, 95% Cl, 2.65−31.76, P=0.0005;, respectively). Age, preferred language, marital status, family history of breast cancer, and race were not found to be significant predictors of enrollment in therapeutic clinical trials. CONCLUSION: While enrollment of eligible breast cancer patients onto therapeutic clinical trials at City of Hope is high (58%), overall the proportion going onto clinical trials remains low (80/418, 19%), though higher than national averages. We found that the majority of patients did not enroll due to lack of availability of a suitable trial, ineligibility, or lack of offering of trial enrollment by the treating MD. Barriers to cancer clinical trial accrual should be prospectively identified and addressed in future studies, with the hope of leading to more vigorous enrollment. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-11-06.