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

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

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.

Study Overview

• Status: Unknown
• Conditions: Renal Cell Carcinoma
• Intervention / Treatment: Drug: Nivolumab; Drug: Ipilimumab

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation
    • Recruiting
    • N.N. Blokhin Russian Cancer Research Center
    • Contact: Maria Volkova, MD
  • Moscow, Russian Federation
    • Recruiting
    • Russian Scientific Center of Roentgenoradiology
    • Contact: Rustem Gafanov, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Cytologically proven clear-cell RCC
2. CT-confirmed measurable primary tumor less than 4 cm and no evidence of extranodal metastatic disease (T1aN0M0)
3. 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
4. No contradictions to nivolumab and ipilimumab
5. Age 18 or older
6. Written informed consent

Exclusion Criteria:

1. prior treatment for RCC
2. pregnant or nursing
3. 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)
4. evidence of metastatic disease
5. local and/or systemic infections requiring antibiotics within 28 days prior to study entry
6. other malignancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nivolumab + Ipilimumab; Patients will receive a combination of ipilimumab, followed by nivolumab for 16 weeks.	Drug: Nivolumab; 3 mg/kg intravenously every 2 weeks during 16 weeks; Other Names: Opdivo; Drug: Ipilimumab; 1 mg/kg intravenously every 3 weeks for four doses; Other Names: Yervoy

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Kidney Cancer Research Bureau

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2019
• Primary Completion (Anticipated): September 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: October 18, 2019
• First Submitted That Met QC Criteria: October 18, 2019
• First Posted (Actual): October 22, 2019

Study Record Updates

• Last Update Posted (Actual): December 23, 2020
• Last Update Submitted That Met QC Criteria: December 22, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Ipilimumab
• Other Study ID Numbers: KCRB16102019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No