Nivolumab in Treating Patients With High-Risk Kidney Cancer Before Surgery
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02595918|
Recruitment Status : Recruiting
First Posted : November 4, 2015
Last Update Posted : August 12, 2019
|Condition or disease||Intervention/treatment||Phase|
|Clear Cell Renal Cell Carcinoma Metastatic Renal Cell Carcinoma Stage I Renal Cell Cancer AJCC v6 and v7 Stage II Renal Cell Cancer AJCC v7 Stage III Renal Cell Cancer AJCC v7 Stage IV Renal Cell Cancer AJCC v7||Procedure: Metastasectomy Procedure: Nephrectomy Biological: Nivolumab||Phase 1|
I. To study the safety and feasibility of preoperative nivolumab administration in subjects with resectable, high-risk, non-metastatic and metastatic renal cell carcinoma undergoing planned cytoreductive nephrectomy or metastasectomy.
I. To assess overall response rate in patients receiving preoperative nivolumab.
II. To assess recurrence free survival at 2 years in patients receiving preoperative nivolumab in patients with high-risk, non-metastatic disease.
I. To evaluate the association between baseline tumor mutational burden and both immune infiltration and radiographic tumor response to nivolumab.
II. To explore predicted and expressed tumor neoantigens and their correlation with radiographic tumor response to nivolumab.
III. To explore the association between the predicted immune signature (via ribonucleic acid sequencing [RNAseq]) in the tumor microenvironment with radiographic tumor response to nivolumab.
IV. To determine whether changes in the tumor microenvironment before, during, and after therapy are associated with response.
V. To assess the potential association between PD-L1 expression (by immunohistochemistry [IHC]) and radiographic tumor response to nivolumab.
Patients receive nivolumab intravenously (IV) over 60 minutes on days -56, -42, -28, and -14 in the absence of disease progression or unacceptable toxicity. Patients then undergo nephrectomy or metastasectomy on day 0.
After completion of study treatment, patients are followed up at 14-28 days, at 90 days, and then at 24-28 months.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||29 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study of Preoperative Nivolumab in High-Risk Non-Metastatic and Metastatic Renal Cell Carcinoma|
|Actual Study Start Date :||May 19, 2016|
|Estimated Primary Completion Date :||April 30, 2020|
Experimental: Treatment (nivolumab)
Patients receive nivolumab IV over 60 minutes on days -56, -42, -28, and -14 in the absence of disease progression or unacceptable toxicity. Patients then undergo nephrectomy or metastasectomy on day 0.
- Feasibility of a patient to receive at least 3 doses of nivolumab and complete surgery without significant delay attributable to nivolumab therapy [ Time Frame: Up to 8 weeks ]Significant delay is defined as delay of > 112 days after the first dose of nivolumab, which would constitute a doubling of the 'planned delay' that our design requires for administration of preoperative therapy (56 days).
- Incidence of toxicity [ Time Frame: Up to 90 days ]Will be defined per Common Terminology Criteria for Adverse Events version 4.0 (version 5.0 beginning April 1, 2018). All patients who receive any amount of the study drug will be evaluable for toxicity. Toxicity will be summarized according to grade as a number and percentage of participants. Each adverse event will be summarized as the highest grade experienced for an individual patient. Descriptive statistics will be used for summaries of the reported toxicity.
- Surgical complications [ Time Frame: Up to 90 days ]Defined per Clavien-Dindo Complications score.
- Overall response rate [ Time Frame: Up to 2 years ]WIll be measured by radiographic response assessment for each cross sectional scan obtained using Response Evaluation Criteria in Solid Tumors 1.1. All patients will be categorized per their best radiographic response (complete response/partial response/stable disease/progressive disease), and the frequency of each category will be determined. The overall response rate will be calculated by dividing the sum of all patients achieving a complete response or confirmed partial response by the number of all evaluable patients.
- Recurrence free survival [ Time Frame: Time from the start of the treatment to recurrence or death, assessed up to 2 years ]Recurrence free survival will be estimated using the Kaplan-Meier method. Two-year recurrence free survival will be provided along with 95% confidence interval. Patients who are unable to undergo nephrectomy or metastasectomy for any reason will not be included in the analysis.
- Feasibility of biomarker analysis [ Time Frame: Up to 90 days ]Will be defined as ability to procure sufficient quantity and quality of tumor tissue and peripheral blood for testing. Will be descriptive or graphical in nature, and are designed to generate new hypotheses to be tested in future clinical studies. When parameters of immune response are measured, continuous variables will be summarized with means and standard deviations. Dichotomous and categorical variables will be summarized using proportions with exact 95% confidence intervals and counts, respectively. For each patient, comparisons in the pre and post-nivolumab responses will be compared using paired t-tests (or Wilcoxon signed rank tests if appropriate) for continuous variables.
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): NCT02595918
|United States, New York|
|Memorial Sloan Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: Martin H. Voss 212-639-7202 email@example.com|
|Principal Investigator: Martin H. Voss|
|Principal Investigator:||Martin H Voss||Memorial Sloan Kettering Cancer Center|