Study of Neoadjuvant Nivolumab in Patients With Non-metastatic Stage II-IV Clear Cell Renal Cell Carcinoma

Study Overview
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Brief Summary
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This study will evaluate the use of nivolumab before surgery in patients with high-risk clear cell renal cell carcinoma who are eligible for nephrectomy. Nivolumab is an antibody that may help activate the immune system by blocking the function of an inhibitory molecule, Programmed cell death-1 (PD-1).

Official Title
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Phase I Study of Neoadjuvant Nivolumab in Patients With Non-metastatic High-risk Clear Cell Renal Cell Carcinoma

Conditions
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Clear Cell Renal Cell Carcinoma

Intervention / Treatment
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* Drug: Nivolumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (abbreviated): Confirmed non-metastatic high-risk clear cell renal cell carcinoma (T2a-T4NanyM0 or TanyN1M0) Schedule to undergo either partial or radical nephrectomy as part of treatment plan Patient agrees to have a tumor biopsy ECOG performance status of 0 or 1 Adequate organ and marrow function defined by study-specified laboratory tests Must use acceptable form of birth control while on study and for approximately 31 weeks post-treatment completion Willingness and ability to comply with scheduled visits, treatment plans, lab tests and other study procedures Exclusion Criteria (abbreviated): Other active malignancies within last 3 years (with some exceptions for skin, prostate, cervical, or breast cancer) Need for urgent or emergent nephrectomy to relieve symptoms Prior treatment for RCC including surgery, radiation, thermoablation or systemic therapy Surgery within 28 days of starting study treatment (some exceptions for minor procedures) Received live vaccine for infectious diseases within 28 days of starting study treatment Prior treatment with any antibody or drug targeting T-cell costimulation or immune checkpoint pathways (anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, etc) Use of immunosuppressive doses of systemic medications within 14 days prior to starting study drug. Current use of immunosuppressive agents History of severe hypersensitivity reaction to other monoclonal antibodies Current signs or symptoms of severe progressive or uncontrolled hepatic, hematologic, gastrointestinal, endocrine, pulmonary or cardiac disease other than directly related to RCC Uncontrolled psychiatric illness/social situations that would limit compliance with study requirements. Active infection requiring therapy. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness. Positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA). History of autoimmune disease or syndrome requiring systemic steroids or immunosuppressants (some exceptions apply). Pulse oximetry of <92% on room air Pregnant or breastfeeding women

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nivolumab<br>3 mg/kg, IV (in the vein) on day 1 of each 2-week cycle, for a total of 3 doses prior to nephrectomy. | Drug: Nivolumab<br>* 3 mg/kg, IV (in the vein) on day 1 of each 2-week cycle, for a total of 3 doses prior to nephrectomy.<br>* Other names: Opdivo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety as assessed by number of participants experiencing adverse events | Number of participants experiencing any adverse event as defined by Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0) | From the first dose of nivolumab treatment through 100 days post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Tumor Response Rate (by RECIST) | Number of patients achieving a complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST) | Assessed at baseline, prior to surgery, and 3 months after surgery | 
| Objective Tumor Response Rate (by irRC) | Number of patients achieving a complete response (CR) or partial response (PR) by immune-related response criteria (irRC) | Assessed at baseline, prior to surgery, and 3 months after surgery | 
| Quality of Life as assessed by the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) -15 questionnaire | Total score range 0-60 with higher scores indicating a less symptomatic respondent. | Baseline, 2 weeks, 4 weeks, prior to surgery, and at 1-, 3-, 6-, and 12-months after surgery | 
| Metastasis-Free Survival | Number of months without evidence of metastasis. | 12 months post-operatively, then every 6 months for 5 years | 
| Overall Survival | Number of months alive. | 12 months post-operatively, then every 6 months for 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunotherapy, PD-1, anti-PD-1, antibody, Kidney Cancer, RCC, non-metastatic