Abstract
Background
The American Society of Clinical Oncology and Friends of Cancer Research submitted recommendations to the FDA to reduce barriers in clinical trial participation. They proposed the removal of several specific exclusion criteria, including brain metastasis. Clinical trials involving small cell lung cancer (SCLC) have varying exclusion criteria regarding brain metastasis.
Methods
We completed an online search of clinicaltrials.gov for the query “SCLC, extensive stage.” The trials were classified into a group of strict exclusion, allowed only if treated, allowed without treatment, or undefined. Relationships between status of brain metastasis in exclusion criteria and study characteristics (trial status, trial design, sponsor, location, and treatment groups) were investigated by Chi-squared test. The trends of exclusion status were investigated by a comparison against the variable time.
Results
Of the 204 eligible trials, 32 strictly excluded any form or history of CNS metastases, 129 allowed patients that are undergoing or have undergone CNS-specific therapy, 9 allowed patients without any CNS-specific therapy, and 34 did not mention any criteria involving CNS metastases. Studies conducted outside the United States and with single systemic therapy were associated with strict exclusion of brain metastasis (p = 0.026 and 0.039, respectively). The proportion of clinical trials with strict exclusion has remained around 15% for the past few decades.
Conclusion
Non-US and single systemic therapy studies are more commonly associated with strict exclusion of brain metastasis in ES-SCLC trials. The strict exclusion of brain metastases in clinical trials has remained relatively constant for the past few decades.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
American Cancer Society. Key Statistics for Small Cell Lung Cancer [Internet]. Cancer.org.; [cited 2019 Jul 10]. https://www.cancer.org/cancer/small-cell-lung-cancer/about/key-statistics.html. Accessed 22 July 2019
ASCO and friends submit recommendations to FDA aimed at reducing barriers to clinical trial participation [Internet]. ASCO and Friends submit recommendations to FDA aimed at reducing barriers to clinical trial participation—the ASCO Post. 8/9/2018 [cited 2019Jul11]. https://www.ascopost.com/News/59150. Accessed 21 Sept 2019
Kim ES, Bruinooge SS, Roberts S, Ison G, Lin NU, Gore L, Uldrick TS, Lichtman SM, Roach N, Beaver JA, Sridhara R, Hesketh PJ, Denicoff AM, Garrett-Mayer E, Rubin E, Multani P, Prowell TM, Schenkel C, Kozak M, Allen J, Sigal E, Schilsky RL (2017) Broadening eligibility criteria to make clinical trials more representative: American Society of Clinical Oncology and Friends of Cancer Research Joint Research Statement. J Clin Oncol 35:3737–3744
Lichtman SM, Harvey RD, Damiette Smit MA, Rahman A, Thompson MA, Roach N, Schenkel C, Bruinooge SS, Cortazar P, Walker D, Fehrenbacher L (2017) 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. J Clin Oncol 35:3753–3759
Lin NU, Lee EQ, Aoyama H, Barani IJ, Baumert BG, Brown PD, Harris GJ (2013) Challenges relating to solid tumour brain metastases in clinical trials, part 1: patient population, response, and progression A report from the RANO group. Lancet Oncol 14(10):e396–e406
Lin NU, Prowell T, Tan AR, Kozak M, Rosen O, Amiri-Kordestani L, White J, Sul J, Perkins L, Beal K, Gaynor R, Kim ES (2017) Modernizing clinical trial eligibility criteria: recommendations of the American Society of Clinical Oncology-Friends of Cancer Research Brain Metastases Working Group. J Clin Oncol 35:3760–3773
McCoach CE, Berge EM, Lu X, Baron AE, Camidge DR (2016) A Brief Report of the status of central nervous system metastasis enrollment criteria for advanced non-small cell lung cancer clinical trials: a review of the ClinicalTrials.gov Trial registry. J Thorac Oncol 11(3):407–413. https://doi.org/10.1016/j.jtho.2015.10.024
Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS, Kim DW, Ou SI, Pérol M, Dziadziuszko R, Rosell R, Zeaiter A, Mitry E, Golding S, Balas B, Noe J, Morcos PN, Mok T, ALEX Trial Investigators (2017) Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med 377:829–838
Acknowledgements
We thank the faculty and staff of the 2019 SERF program for assisting our research.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
All authors declared no conflict of interest.
Ethical approval
This article does not contain any studies with human participants or animals performed by any of the authors.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Wang, A., Komiya, T. Brain metastasis as exclusion criteria in clinical trials involving extensive-stage small cell lung cancer. J Cancer Res Clin Oncol 145, 3099–3104 (2019). https://doi.org/10.1007/s00432-019-03034-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00432-019-03034-7