Nivolumab in Treating Patients With Localized Kidney Cancer Undergoing Nephrectomy
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|ClinicalTrials.gov Identifier: NCT03055013|
Recruitment Status : Active, not recruiting
First Posted : February 16, 2017
Last Update Posted : June 10, 2022
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Renal Cell Carcinoma Sarcomatoid Renal Cell Carcinoma Stage II Renal Cell Cancer AJCC v7 Stage III Renal Cell Cancer AJCC v7 Unclassified Renal Cell Carcinoma||Procedure: Nephrectomy Biological: Nivolumab Other: Patient Observation Other: Quality-of-Life Assessment Other: Questionnaire Administration||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||766 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Single (Outcomes Assessor)|
|Official Title:||A Phase 3 RandOmized Study Comparing PERioperative Nivolumab vs. Observation in Patients With Renal Cell Carcinoma Undergoing Nephrectomy (PROSPER RCC)|
|Actual Study Start Date :||February 2, 2017|
|Estimated Primary Completion Date :||November 30, 2023|
|Estimated Study Completion Date :||November 30, 2023|
Experimental: Arm I (nivolumab, nephrectomy)
Patients receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 14 days for 2 cycles. Patients then undergo partial or radical nephrectomy 7-28 days later. Patients then receive nivolumab over 30 IV on day 1. Treatment repeats every 14 days for 6 cycles, and then every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
Patients enrolled after Amendment 4 receive nivolumab IV over 30 minutes on day 1. Patients then undergo partial or radical nephrectomy 7-28 days later. Patient then receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 4 weeks for up to 9 cycles in the absence of disease progression or unacceptable toxicity.
Other: Quality-of-Life Assessment
Other: Questionnaire Administration
Active Comparator: Arm II (nephrectomy)
Patients undergo partial or radical nephrectomy within 8 weeks after registration followed by observation.
Other: Patient Observation
Other: Quality-of-Life Assessment
Other: Questionnaire Administration
- Event-free survival (EFS) [ Time Frame: Time from randomization to disease recurrence or death from any cause, assessed up to 10 years ]Will be assessed among all randomized patients using a stratified log rank test, with nominal one-sided type I error of 2.5%. The type I error will be adjusted for interim analyses.
- Overall survival [ Time Frame: Time from randomization to death from any cause, assessed up to 10 years ]
- RFS among patients with clear cell cancer [ Time Frame: Up to 10 years ]The stratified logrank test will be used.
- Incidence of toxicity [ Time Frame: Up to 10 years ]Graded per Common Criteria for Adverse Events (CTCAE) version (v)4.0. (Starting April 1, 2018, Cancer Therapy Evaluation Program Adverse Event Reporting System [CTEP-AERS] reporting will use CTCAE v5). Adverse events will be described separately for patients treated on each arm to evaluate safety and tolerability.
- Primary tumor's expression of PD-L1 [ Time Frame: Baseline to up to 10 years ]The percentage of cells exhibiting cell-surface staining for PD-L1 will be scored. PD-L1 positivity will be defined per specimen by a 5% expression threshold. Additional analyses will assess the 1% and 10% threshold levels. Information with respect to the relative abundance and location (peritumoral/intratumoral) of immune cell (macrophage and lymphocyte) PD-L1 staining will be captured. The expression-by-treatment interaction will be tested using a proportional hazards model. McNemar's Test will be used to explore categorical changes within each treatment group.
- Expression of PD-L1 on tumor tissue at recurrence [ Time Frame: Up to 10 years ]
- Pharmacokinetic analysis of nivolumab [ Time Frame: On day 1 of cycles 1-3, 5, 7 and the first 2 follow-up visits ]Serum concentration analyses for nivolumab will be performed by validated bio-analytical methods for nivolumab.
- Change in patient-reported symptoms and toxicities [ Time Frame: Baseline to up to 10 years ]Using the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy (NCCN/FACT) Kidney Symptom Index-19 (NFKSI-19) and items from the PRO-CTCAE pool of items measuring patient-reported toxicity. We will describe the severity, interference, and (as appropriate) frequency rates, along with response rates at each time point. Change in symptoms will be tested using a two-sided Wilcoxon rank sum test with Type I error of 3%. Change in physical function will be tested using a two-sided Wilcoxon rank sum test with Type I error of 1%. Changes in NFKSI-19 and PROMIS Physical Function scores from baseline to pre-nephrectomy among patients randomized to nivolumab and will be explored using a Wilcoxon signed rank test. Differences in scores post-nephrectomy between the arms will be described and tested using a Wilcoxon rank-sum test. Differences in the pattern of change over time in NFKSI-19 and PROMIS Physical Function scores will be examined using mixed effects models.
- Absolute T cell clonotype abundance [ Time Frame: Up to 10 years ]Will be determined by assessing the number of unique clonotypes identified. The data will be summarized descriptively and graphically.
- Change in T cell repertoire [ Time Frame: From diagnosis to on therapy or to time of recurrence, assessed up to 10 years ]Morisita's distance will be used as utilized by Cha and colleagues. Morisita's distance ranges from 0-1. Zero indicates minimal change in T cell repertoire (TCR) repertoire size (number of unique clonotypes) and 1 indicates maximal change after treatment.
- T cell receptor (TCR) diversity using change in repertoire size per patient [ Time Frame: Baseline to up to 10 years ]The top 25% of unique clonotypes will be identified by sorting for clone frequency. Fold change after recurrence will be measured and plotted on a logarithmic scale.
- Change in cytokine levels in patients randomized to the nivolumab arm [ Time Frame: Baseline to up to 10 years ]Differences in RFS between patients with and without robust CD8 infiltration will be explored. A Cox proportional hazards model will be used to test the interaction between treatment and cytokine changes.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03055013
|Principal Investigator:||Lauren Harshman||ECOG-ACRIN Cancer Research Group|