Eligibility and Radiologic Assessment for Adjuvant Clinical Trials in Kidney Cancer

Purpose: To harmonize the eligibility criteria and radiologic disease assessment definitions in clinical trials of adjuvant therapy for renal cell carcinoma (RCC).

Method: On November 28, 2017, US-based experts in RCC clinical trials, including medical oncologists, urologic oncologists, regulators, biostatisticians, radiologists, and patient advocates, convened at a public workshop to discuss eligibility for trial entry and radiologic criteria for assessing disease recurrence in adjuvant trials in RCC. Multiple virtual meetings were conducted to address the issues identified at the workshop.

Results The key workshop conclusions for adjuvant RCC therapy clinical trials were as follows. First, patients with non–clear cell RCC could be routinely included, preferably in an independent cohort. Second, patients with T3-4, N+M0, and microscopic R1 RCC tumors may gain the greatest advantages from adjuvant therapy. Third, trials of agents not excreted by the kidney should not exclude patients with severe renal insufficiency. Fourth, therapy can begin 4 to 16 weeks after the surgical procedure. Fifth, patients undergoing radical or partial nephrectomy should be equally eligible. Sixth, patients with microscopically positive soft tissue or vascular margins without gross residual or radiologic disease may be included in trials. Seventh, all suspicious regional lymph nodes should be fully resected. Eighth, computed tomography should be performed within 4 weeks before trial enrollment; for patients with renal insufficiency who cannot undergo computed tomography with contrast, noncontrast chest computed tomography and magnetic resonance imaging of the abdomen and pelvis with gadolinium should be performed. Ninth, when feasible, biopsy should be undertaken to identify any malignant disease. Tenth, when biopsy is not feasible, a uniform approach should be used to evaluate indeterminate radiologic findings to identify what constitutes no evidence of disease at trial entry and what constitutes radiologic evidence of disease. Eleventh, a uniform approach for establishing the date of recurrence should be included in any trial design. Twelfth, patient perspectives on the use of placebo, conditions for unblinding, and research biopsies should be considered carefully during the conduct of an adjuvant trial.

Conclusions and Relevance: The discussions suggested that a uniform approach to eligibility criteria and radiologic disease assessment will lead to more consistently interpretable trial results in the adjuvant RCC therapy setting.

Sundeep Agrawal, MD1; Naomi B. Haas, MD2; Mohammadhadi Bagheri, MD3; Brian R. Lane, MD, PhD4; Jonathan Coleman, MD5; Hans Hammers, MD6; Gennady Bratslavsky, MD7; Cynthia Chauhan,, MSW8; Lauren Kim, MD3; Venkatesh P. Krishnasamy, MD3; Jamie Marko, MD3; Virginia Ellen Maher, MD1; Amna Ibrahim, MD1; Frank Cross Jr, MA, MT (ASCP)1; Ke Liu, MD, PhD9; Julia A. Beaver, MD1; Richard Pazdur, MD10; Gideon M. Blumenthal, MD10; Harpreet Singh, MD1; Elizabeth R. Plimack, MD11; Toni K. Choueiri, MD12; Robert Uzzo, MD11; Andrea B. Apolo, MD3

Author Information
1. Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland
2. Abramson Cancer Center, Philadelphia, Pennsylvania
3. Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
4. Spectrum Health Cancer Center, Grand Rapids, Michigan
5. Memorial Sloan Kettering Cancer Center, New York, New York
6. University of Texas Southwestern Medical Center, Dallas
7. Department of Urology, SUNY Upstate Medical University, Syracuse, New York
8. Heart Failure Society of America, Rockville, Maryland
9. Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland
10. Oncology Center of Excellence, Food and Drug Administration, Silver Spring, Maryland
11. Fox Chase Cancer Center, Philadelphia, Pennsylvania
12. Dana-Farber Cancer Institute, Boston, Massachusetts

JAMA Oncol. Published online November 21, 2019. doi:https://doi.org/10.1001/jamaoncol.2019.4117