Nivolumab and Ipilimumab in T1aN0M0 Renal Cell Carcinoma Patients Ineligible for Surgical Treatment.

Study Overview
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Brief Summary
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The aim of this Phase 2 study is to evaluate the efficacy and safety of nivolumab, an anti-PD-1 antibody, and ipilimumab, an anti-CTLA-4 antibody, in T1aN0M0 clear-cell RCC patients ineligible for surgical treatment.

Detailed Description
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Surgery remains the standard curative-intent therapy for localized renal cell carcinoma (RCC). Thus, systemic therapy for RCC should still be considered only in patients who have contraindications to surgery. Results of Phase 3 CheckMate 214 study showed that a combination of nivolumab and ipilimumab has a significant impact on tumor burden in intermediate- and poor-risk metastatic RCC patients with a complete response rate of 11% (Motzer et al. Lancet Oncology 2019). Median time to objective response was 2.8 months. Among all complete responders to nivolumab plus ipilimumab in the intention-to-treat population, 5% achieved a complete response at the first scan, whereas most converted from the partial response at a median of 6.9 months or from the stable disease at a median of 11.3 months. We hypothesize that this combination could completely eliminate primary tumors in patients with small primary (less than 4 cm) ineligible for surgical treatment. There are no studies evaluating checkpoint inhibitors in this setting in RCC patients.

Official Title
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A Phase 2 Pilot Study of the Efficacy and Safety of Nivolumab and Ipilimumab in T1aN0M0 Renal Cell Carcinoma Patients Ineligible for Surgical Treatment.

Conditions
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Renal Cell Carcinoma

Intervention / Treatment
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* Drug: Nivolumab
* Drug: Ipilimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cytologically proven clear-cell RCC CT-confirmed measurable primary tumor less than 4 cm and no evidence of extranodal metastatic disease (T1aN0M0) Inability to perform surgery for any reason (functional single kidney with a central, high-complexity RCC, high risk of nephrectomy and dialysis, patients with complex coagulation disorders, etc.) or preference of patient is to have no surgery for any reason No contradictions to nivolumab and ipilimumab Age 18 or older Written informed consent Exclusion Criteria: prior treatment for RCC pregnant or nursing history of serious hypertension, cardiac arrhythmia, congestive heart failure, angina pectoris, or another severe cardiovascular disease (i.e., New York Heart Association class III or IV) evidence of metastatic disease local and/or systemic infections requiring antibiotics within 28 days prior to study entry other malignancy

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 + Ipilimumab<br>Patients will receive a combination of ipilimumab, followed by nivolumab for 16 weeks. | Drug: Nivolumab<br>* 3 mg/kg intravenously every 2 weeks during 16 weeks<br>* Other names: Opdivo;Drug: Ipilimumab<br>* 1 mg/kg intravenously every 3 weeks for four doses<br>* Other names: Yervoy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response Rate | percentage of patients with localized RCC who have no tumor in kidney | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | percentage of patients with localized RCC who have no tumor in kidney or tumor shrinkage more than 30% | 16 weeks | 
| 3-year disease-free survival rate | percentage of patients who are disease free at 3 years after treatment start | 3 years | 
| 5-year survival rate | percentage of patients who are alive at 5 years after treatment start | 5 years | 
| Rate of adverse events | percentage of patients who have adverse events | 16 weeks |