National Cancer Institute (NCI) implementation of the American Society of Clinical Oncology (ASCO) and Friends of Cancer Research (Friends) broadening clinical trials eligibility criteria.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6518-6518
Author(s):  
Andrea M. Denicoff ◽  
S. Percy Ivy ◽  
Katherine H. Worthington ◽  
Jinxiu Zhao ◽  
Nita Seibel ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Brain Metastases ◽  
Hiv Infection ◽  
National Cancer Institute ◽  
Late Phase ◽  
Eligibility Criteria ◽  
Minimum Age ◽  
Liver And Kidney ◽  
Localized Disease ◽  
American Society

6518 Background: The 2017 ASCO/Friends eligibility criteria guidelines recommend inclusiveness to promote generalizable trial results and clear rationale for necessary exclusion. These guidelines focused on brain metastases, minimum age for enrollment, HIV infection, and organ dysfunction and prior and concurrent malignancies. In September 2018, the NCI Cancer Therapy Evaluation Program (CTEP) implemented modernized protocol template language to operationalize these criteria. We evaluated utilization of the new language among CTEP-sponsored treatment trials. Methods: We evaluated protocols first approved by CTEP between 11/01/2018 and 4/30/2020. The most recent approved protocol version was evaluated for consistency with the new template language for brain metastases, HIV infection, prior or concurrent malignancies, minimum age, and cardiac, liver and kidney function. If a particular criterion was not relevant for a trial, it was not included in the analysis. We did not score age in pediatric or adult-specific trials (e.g. prostate). Results: 122 trials (71% early and 29% late phase) were identified and included in the analysis. Compliance with the new criteria language ranged from a high of 87.7% for liver function to a low of 11.5% for “new or progressive brain metastases” (table). Modernized criteria language was lacking in nearly 46% of trials in the use of concurrent or prior malignancy criteria and 31% of trials for the cardiac criteria. Of the 87 trials for non-localized disease or non-brain tumor trials, 64.4% did not address brain metastases, leaving it to investigator discretion. Thus, 75.9% of trials could theoretically enroll patients with brain metastases. Only 6 trials were considered relevant for patients < 18 years old; 50% were consistent with the age criterion (not shown in table). Conclusions: Implementing ASCO/Friends eligibility criteria requires focused reviews during protocol development to ensure compliance. CTEP is using these findings to continue to improve its protocol review processes to broaden eligibility in clinical trials. Maximizing opportunities for diverse populations to participate in trials is a priority for the National Cancer Institute and CTEP will continue efforts to achieve this goal.[Table: see text]

Modernizing Clinical Trial Eligibility Criteria: Recommendations of the American Society of Clinical Oncology–Friends of Cancer Research Brain Metastases Working Group

2017 ◽  
Vol 35 (33) ◽  
pp. 3760-3773 ◽  
Author(s):  
Nancy U. Lin ◽  
Tatiana Prowell ◽  
Antoinette R. Tan ◽  
Marina Kozak ◽  
Oliver Rosen ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Brain Metastases ◽  
Working Group ◽  
Study Entry ◽  
Leptomeningeal Disease ◽  
Eligibility Criteria ◽  
Prior Therapy ◽  
Investigational Therapies ◽  
Minimum Age ◽  
American Society

Purpose Broadening trial eligibility to improve accrual and access and to better reflect intended-to-treat populations has been recognized as a priority. Historically, patients with brain metastases have been understudied, because of restrictive eligibility across all phases of clinical trials. Methods In 2016, after a literature search and series of teleconferences, a multistakeholder workshop was convened. Our working group focused on developing consensus recommendations regarding the inclusion of patients with brain metastases in clinical trials, as part of a broader effort that encompassed minimum age, HIV status, and organ dysfunction. The working group attempted to balance the needs of protecting patient safety, facilitating access to investigational therapies, and ensuring trial integrity. On the basis of input at the workshop, guidelines were further refined and finalized. Results The working group identified three key populations: those with treated/stable brain metastases, defined as patients who have received prior therapy for their brain metastases and whose CNS disease is radiographically stable at study entry; those with active brain metastases, defined as new and/or progressive brain metastases at the time of study entry; and those with leptomeningeal disease. In most circumstances, the working group encourages the inclusion of patients with treated/stable brain metastases in clinical trials. A framework of key considerations for patients with active brain metastases was developed. For patients with leptomeningeal disease, inclusion of a separate cohort in both early-phase and later-phase trials is recommended, if CNS activity is anticipated and when relevant to the specific disease type. Conclusion Expanding eligibility to be more inclusive of patients with brain metastasis is justified in many cases and may speed the development of effective therapies in this area of high clinical need.

scholarly journals Broadening Eligibility Criteria to Make Clinical Trials More Representative: American Society of Clinical Oncology and Friends of Cancer Research Joint Research Statement

2017 ◽  
Vol 35 (33) ◽  
pp. 3737-3744 ◽  
Author(s):  
Edward S. Kim ◽  
Suanna S. Bruinooge ◽  
Samantha Roberts ◽  
Gwynn Ison ◽  
Nancy U. Lin ◽  
...  
Keyword(s):  
Cancer Research ◽  
Brain Metastases ◽  
Dose Finding ◽  
Joint Research ◽  
Eligibility Criteria ◽  
Investigational Agent ◽  
The Us ◽  
Minimum Age ◽  
Working Groups ◽  
American Society

Purpose The primary purposes of eligibility criteria are to protect the safety of trial participants and define the trial population. Excessive or overly restrictive eligibility criteria can slow trial accrual, jeopardize the generalizability of results, and limit understanding of the intervention’s benefit-risk profile. Methods ASCO, Friends of Cancer Research, and the US Food and Drug Administration examined specific eligibility criteria (ie, brain metastases, minimum age, HIV infection, and organ dysfunction and prior and concurrent malignancies) to determine whether to modify definitions to extend trials to a broader population. Working groups developed consensus recommendations based on review of evidence, consideration of the patient population, and consultation with the research community. Results Patients with treated or clinically stable brain metastases should be routinely included in trials and only excluded if there is compelling rationale. In initial dose-finding trials, pediatric-specific cohorts should be included based on strong scientific rationale for benefit. Later phase trials in diseases that span adult and pediatric populations should include patients older than age 12 years. HIV-infected patients who are healthy and have low risk of AIDS-related outcomes should be included absent specific rationale for exclusion. Renal function criteria should enable liberal creatinine clearance, unless the investigational agent involves renal excretion. Patients with prior or concurrent malignancies should be included, especially when the risk of the malignancy interfering with either safety or efficacy endpoints is very low. Conclusion To maximize generalizability of results, trial enrollment criteria should strive for inclusiveness. Rationale for excluding patients should be clearly articulated and reflect expected toxicities associated with the therapy under investigation.

A multicentered population-based analysis of outcomes of patients with metastatic renal cell carcinoma (mRCC) who do not meet eligibility criteria for clinical trials.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 353-353 ◽  
Author(s):  
Daniel Yick Chin Heng ◽  
Toni K. Choueiri ◽  
Jae-Lyun Lee ◽  
Lauren Christine Harshman ◽  
Georg A. Bjarnason ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Brain Metastases ◽  
Clear Cell ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Progression Free Survival ◽  
Exclusion Criteria ◽  
Eligibility Criteria ◽  
Number Of Patients

353 Background: Clinical trials have strict eligibility criteria to maintain internal validity. These criteria exclude many patients to whom the trial results are later applied to in clinical practice. Patients that do not meet eligibility criteria are poorly characterized. Methods: mRCC patients treated with VEGF targeted therapy were retrospectively deemed ineligible for clinical trials (according to commonly used inclusion/exclusion criteria) if they had a Karnofsky Performance Status (KPS) < 70%, brain metastases, non-clear cell histology, hemoglobin ≤ 9 g/dL, creatinine > 2x the upper limit of normal, platelet count of < 100x103/uL, neutrophil count < 1500/mm3 or corrected calcium ≤ 12 mg/dL. Results: 894/2076 (43%) patients were deemed ineligible for clinical trials by the above criteria. Between ineligible versus eligible patients, the response rate, median progression free survival (PFS) and median overall survival of first-line targeted therapy were 21% vs 29%, 5.2 vs 8.8 months and 14.5 vs 28.8 months (all p < 0.0001), respectively. Second-line PFS (if applicable) was 3.2 months in the trial ineligible vs 4.4 months in the trial eligible patients (p = 0.0074). When adjusted by the Heng et al prognostic categories, the hazard ratio for death between trial ineligible vs trial eligible patients was 1.621 (95% CI = 1.431–1.836, p < 0.0001). If only KPS, brain metastases and non-clear cell histology were used as exclusion criteria, 672 (32%) patients were excluded and the results were similar. Conclusions: The number of patients that are ineligible for clinical trials is high and their outcomes are inferior. Designing more inclusive clinical trials for this “ineligible” patient population are needed. [Table: see text]

scholarly journals Clinical Trial Eligibility Criteria and Recently Approved Cancer Therapies for Patients With Brain Metastases

2022 ◽  
Vol 11 ◽  
Author(s):  
Aaron C. Tan ◽  
Drexell H. Boggs ◽  
Eudocia Q. Lee ◽  
Michelle M. Kim ◽  
Minesh P. Mehta ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Brain Metastases ◽  
Real World ◽  
Treatment Options ◽  
Late Phase ◽  
Leptomeningeal Carcinomatosis ◽  
Precision Oncology ◽  
Eligibility Criteria ◽  
Clinical Trial Evidence ◽  
Trial Evidence

Brain metastases cause significant morbidity and mortality in patients with advanced cancer. In the era of precision oncology and immunotherapy, there are rapidly evolving systemic treatment options. These novel therapies may have variable intracranial efficacy, and patients with brain metastases remain a population of special interest. Typically, only patients with stable, asymptomatic and/or treated brain metastases are enrolled in clinical trials, or may be excluded altogether, particularly in the setting of leptomeningeal carcinomatosis. Consequently, this leads to significant concerns on the external validity of clinical trial evidence to real-world clinical practice. Here we describe the current trends in cancer clinical trial eligibility for patients with brain metastases in both early and late phase trials, with a focus on targeted and immunotherapies. We evaluate recent newly FDA approved therapies and the clinical trial evidence base leading to approval. This includes analysis of inclusion and exclusion criteria, requirements for baseline screening for brain metastases, surveillance cerebral imaging and incorporation of trial endpoints for patients with brain metastases. Finally, the use of alternative sources of data such as real-world evidence with registries and collaborative studies will be discussed.

scholarly journals Modernizing Clinical Trial Eligibility Criteria: Recommendations of the American Society of Clinical Oncology–Friends of Cancer Research HIV Working Group

2017 ◽  
Vol 35 (33) ◽  
pp. 3774-3780 ◽  
Author(s):  
Thomas S. Uldrick ◽  
Gwynn Ison ◽  
Michelle A. Rudek ◽  
Ariela Noy ◽  
Karl Schwartz ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
National Cancer Institute ◽  
Working Group ◽  
Patient Population ◽  
Cancer Therapeutics ◽  
Exclusion Criterion ◽  
Eligibility Criteria ◽  
Investigational Agents

Purpose People with HIV are living longer as a result of effective antiretroviral therapy. Cancer has become a leading cause of morbidity and mortality in this patient population. However, studies of novel cancer therapeutics have historically excluded patients with HIV. Critical review of eligibility criteria related to HIV is required to accelerate development of and access to effective therapeutics for HIV-infected patients with cancer and make studies more generalizable to this patient population. Methods From January through April 2016, the HIV Working Group conducted a series of teleconferences; a review of 46 New Drug Applications from registration studies of unique agents studied in adults with cancer that led to the initial US Food and Drug Administration approval of that agent from 2011 to 2015; and a review of HIV-related eligibility criteria from National Cancer Institute–sponsored studies. Results were discussed and refined at a multistakeholder workshop held May 12, 2016. The HIV Working Group developed recommendations for eligibility criteria that focus on pharmacologic and immunologic considerations in this patient population and that balance patient safety, access to appropriate investigational agents, and study integrity. Results Exclusion of patients with HIV remains common in most studies of novel cancer agents. Models for HIV-related eligibility criteria in National Cancer Institute–sponsored studies are instructive. HIV infection itself should no longer be an exclusion criterion for most studies. Eligibility criteria related to HIV infection that address concurrent antiretroviral therapy and immune status should be designed in a manner that is appropriate for a given cancer. Conclusion Expanding clinical trial eligibility to be more inclusive of patients with HIV is justified in most cases and may accelerate the development of effective therapies in this area of unmet clinical need.

Outcomes of patients with metastatic renal cell carcinoma (mRCC) treated with first-line Immuno-oncology (IO) agents who do not meet eligibility criteria for clinical trials.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5070-5070
Author(s):  
Chun Loo Gan ◽  
Shaan Dudani ◽  
Connor Wells ◽  
Ziad Bakouny ◽  
Nazli Dizman ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Brain Metastases ◽  
Neutrophil Count ◽  
Clear Cell ◽  
Karnofsky Performance Status ◽  
Cell Component ◽  
First Line ◽  
Eligibility Criteria ◽  
Patient Counselling ◽  
Number Of Patients

5070 Background: IO combination therapies [including IOIO and IO/vascular endothelial growth factor inhibitor (IOVE) combinations] in mRCC have been approved based on registration clinical trials that have strict eligibility criteria. The clinical outcomes of trial ineligible patients who are treated with first-line IOIO or IOVE combinations are unknown. Methods: Metastatic RCC patients treated with first-line IOIO or IOVE were retrospectively deemed ineligible for clinical trials (according to commonly used inclusion/exclusion criteria in IO trials) if they had a Karnofsky performance status (KPS) < 70%, no clear-cell component, brain metastases, hemoglobin (Hb) < 9 g/dL, eGFR < 40 mL/min, platelet count of < 100,000/mm3, and/or neutrophil count < 1500/mm3. Time to treatment failure (TTF) and overall survival (OS) were calculated from time of starting first-line IO therapy. Results: Overall, 26% (155/592) of patients in the International mRCC Database Consortium (IMDC) were deemed ineligible for clinical trials by the above criteria. Baseline characteristics are listed in Table. The reasons for ineligibility were: no clear-cell component (34%, 53/155), Hb < 9g/dL (28%, 44/155), eGFR < 40 mL/min (19%, 30/155), brain metastases (19%, 29/155), KPS < 70% (14%, 21/155), platelet < 100,000/mm3 (3%, 4/155) and neutrophil count < 1500/mm3 (0%, 0/155). Between ineligible versus eligible patients, the response rate, median TTF and median OS of first-line IOIO or IOVE was 34% vs 46% (p = 0.02), 4.2 vs 9.7 months (p < 0.01), and 25.3 vs 44.4 months (p < 0.01), respectively. When adjusted by the IMDC prognostic categories, the HR for death between trial ineligible and trial eligible patients was 1.50 (95% CI 1.05-2.14). Conclusions: The number of patients that are ineligible for clinical trials is substantial and their outcomes are inferior. These data may guide patient counselling and specific trials addressing the unmet needs of protocol ineligible patients are warranted. [Table: see text]

scholarly journals OTHR-09. Accelerating Research for Breast Cancer Brain Metastasis and Leptomeningeal Disease through Patient-led Collaborations

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii16-iii16
Author(s):  
Christine Hodgdon ◽  
Laurie Campbell
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Metastatic Breast ◽  
Basic Research ◽  
Leptomeningeal Disease ◽  
Eligibility Criteria ◽  
Cns Metastasis ◽  
Breast Cancer Brain Metastasis

Abstract Patient-driven Initiative of the Metastatic Breast Cancer (MBC) Alliance The Breast Cancer Brain Metastasis (BCBM) Initiative: Marina Kaplan Project launched in June 2020 as an official project of the MBC Alliance which includes 32 nonprofits, 12 industry partners, and 30 individual patient advocates. The Marina Project has grown to include 35members with representation from industry, research institutions, and individual patients. Nearly one-third of the group is comprised of patients living with brain metastases or leptomeningeal disease (LMD). Disparities for Patients Living with BCBM & LMD In the US, approximately 200,000 new cases of brain metastases are diagnosed each year[1]. Approximately 10–15% of patients with MBC will develop brain metastases, and may be as high as 30–50% for certain subtypes[2]. A diagnosis of central nervous system (CNS) metastasis often accelerates an already incurable diagnosis. CNS metastasis are difficult to image and detect, tend to have poorer prognoses with lower overall survival, and are treated with invasive therapies which can have lasting side effects. Furthermore, most clinical trials exclude patients with CNS metastasis which further hinders research. Values and Objectives The overarching goal of this initiative is to accelerate the scope and breadth of evidence-based CNS metastasis research by targeting entities conducting clinical trials and collaborating with them to do the following: (i) Increase the quality and quantity of basic research; (ii) Increase the number of clinical trials in areas where research is lacking; (iii) Diversify the type of clinical trial interventions; (iv) Eliminate restrictive eligibility criteria in clinical trials; (v) Incorporate clinically meaningful trial endpoints [1] Eichler, April F et al. The biology of brain metastases-translation to new therapies. Nature reviews. Clinical oncology vol. 8,6 (2011): 344–56. doi: 10.1038/nrclinonc.2011.58 [2] Brosnan EM, Anders CK. Understanding patterns of brain metastasis in breast cancer and designing rational therapeutic strategies. Ann Transl Med. 2018;6(9):163. doi: 10.21037/atm.2018.04.35

scholarly journals Feasibility of a Centralized Clinical Trials Coverage Analysis: A Joint Initiative of the American Society of Clinical Oncology and the National Cancer Institute

2017 ◽  
Vol 13 (6) ◽  
pp. 395-400 ◽  
Author(s):  
Connie M. Szczepanek ◽  
Patricia Hurley ◽  
Marjorie J. Good ◽  
Andrea Denicoff ◽  
Kelly Willenberg ◽  
...  
Keyword(s):  
Clinical Trials ◽  
National Cancer Institute ◽  
Working Group ◽  
Financial Risk ◽  
Pilot Project ◽  
Support Unit ◽  
Oncology Research ◽  
Coverage Analysis ◽  
Community Forum ◽  
American Society

Purpose: Clinical trial billing compliance is a challenge that is faced by overburdened clinical trials sites. The requirements place institutions and research sites at increased potential for financial risk. To reduce their risk, sites develop a coverage analysis (CA) before opening each trial. For multisite trials, this translates into system-wide redundancies, inconsistencies, trial delays, and potential costs to sites and patients. These factors exacerbate low accrual rates to cancer clinical trials. ASCO and the National Cancer Institute (NCI) collaborated to address this problem. Methods: An ASCO Research Community Forum working group proposed the concept of providing centrally developed CAs to research sites at protocol startup. The group collaborated with NCI and billing compliance experts to hold a symposium for key stakeholders to share knowledge, build skills, provide tools to conduct centralized CAs, and strategize about the next steps. Results: Forty-eight attendees, who represented a range of stakeholders, participated in the symposium. As a result of this initiative, NCI directed the Cancer Trials Support Unit to convene a working group with NCI’s National Clinical Trials Network (NCTN) and Community Oncology Research Program (NCORP) to develop tools and processes for generating CAs for their trials. A CA template with core elements was developed and is being adapted in a pilot project across NCTN Group and NCORP Research Bases. Conclusion: Centralized CAs for multisite trials—using standardized tools and templates—are feasible. They have the potential to reduce risk for patients and sites, forecast budget needs, and help decrease trial startup times that impede patient access and accrual to clinical trials.

Modernizing Clinical Trial Eligibility Criteria: Recommendations of the American Society of Clinical Oncology–Friends of Cancer Research Organ Dysfunction, Prior or Concurrent Malignancy, and Comorbidities Working Group

2017 ◽  
Vol 35 (33) ◽  
pp. 3753-3759 ◽  
Author(s):  
Stuart M. Lichtman ◽  
R. Donald Harvey ◽  
Marie-Anne Damiette Smit ◽  
Atiqur Rahman ◽  
Michael A. Thompson ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cancer Research ◽  
Clinical Trials ◽  
Organ Dysfunction ◽  
Working Group ◽  
Original Data ◽  
Eligibility Criteria ◽  
Multidisciplinary Working ◽  
Potential Benefits ◽  
American Society

Purpose Patients with organ dysfunction, prior or concurrent malignancies, and comorbidities are often excluded from clinical trials. Excluding patients on the basis of these factors results in clinical trial participants who are healthier and younger than the overall population of patients with cancer. Methods ASCO and Friends of Cancer Research established a multidisciplinary working group that included experts in trial design and conduct to examine how eligibility criteria could be more inclusive. The group analyzed current eligibility criteria; conducted original data analysis; considered safety concerns, potential benefits, research, and potential hurdles of this approach through discussion; and reached consensus on recommendations regarding updated eligibility criteria that prioritize inclusiveness without compromising patient safety. Results If renal toxicity and clearance are not of direct treatment-related concern, then patients with lower creatinine clearance values of > 30 mL/min should be included in trials. Inclusion of patients with mild to moderate hepatic dysfunction may be possible when the totality of the available nonclinical and clinical data indicates that inclusion is safe. Ejection fraction values should be used with investigator assessment of a patient’s risk for heart failure to determine eligibility. Patients with laboratory parameters out of normal range as a result of hematologic disease should be included in trials. Measures of patient functional status should be included in trials to better assess fit versus frail patients. Conclusion Expanding inclusion of these patients will increase the number and diversity of patients in clinical trials and result in a more appropriate population of patients.

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