Investigator-Initiated Trial of Combined Ipilimumab, Nivolumab and Stereotactic Radiation in Patients With Metastatic Clear-Cell RCC (ccRCC) Who Have Failed Treatment With Single-Agent Nivolumab

An Investigator-Initiated Trial of Combined Ipilimumab, Nivolumab and Stereotactic Radiation in Patients With Metastatic Clear-Cell RCC (ccRCC) Who Have Failed Treatment With Single-Agent Nivolumab

The purpose of this study is to see if continued nivolumab with the addition of ipilimumab plus hypo-fractionated stereotactic radiation (sTR) of a single lesions results in partial or complete responses in patients with metastatic ccRCC who fail initial treatment with single agent nivolumab.

Study Overview

• Status: Withdrawn
• Conditions: Clear Cell Renal Cell Carcinoma; Metastatic Renal Cell Carcinoma
• Intervention / Treatment: Drug: Nivolumab; Drug: Ipilimumab; Radiation: Steriotactic radiation therapy

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

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:

• Histologically or cytologically confirmed diagnosis of metastatic ccRCC.
• Age 18 years and older
• ECOG 0-1
• Progressive disease after treatment with single-agent nivolumab
• Life expectancy at least 3 months
• Presence of measurable disease per RECIST 1.1 criteria
• Presence of a metastatic lesion greater than 1 cm in size that is amenable to radiation treatment
• Adequate organ system function
• WOCBP and men who are sexually active with WOCBP must agree to use appropriate method(s) of contraception.

Exclusion Criteria:

• Patients are excluded if they have active brain metastases or leptomeningeal metastases (exceptions outlined in the protocol).
• Active, known or suspected autoimmune disease, such as systemic lupus erythematosus, that require treatment with immune suppressing drugs.

Note: Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger

• Presence of a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone or equivalents) or other immunosuppressive medications within 14 days of study drug administration.

Note: Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.

• Unstable angina or uncontrolled congestive heart failure
• Uncontrolled hypercalcemia
• Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• Presence of other malignant diseases, except non-melanoma skin care
• History of allergy to study drug components.
• History of severe hypersensitivity reaction to any monoclonal antibody.
• Anti-cancer treatment including surgery, radiotherapy, chemotherapy, other immunotherapy, or investigational therapy within 14 days of registration.
• Women must not be pregnant or breastfeeding. WOCBP must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 7 days prior to registration.
• Any other medical condition for which treatment with ipilimumab or nivolumab would be medically contraindicated

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 + SRT

Drug: Nivolumab; Nivolumab will be given every 21 days for the first 12 weeks at a dose of 3mg/kg. After 12 weeks, the dose will be 240mg and will be given every 14 days.; Other Names: opdivo; Drug: Ipilimumab; Ipilimumab will be given at a dose of 1mg/kg every 21 days for up to 12 weeks.; Radiation: Steriotactic radiation therapy; The dose of radiation will be 6 Gy daily x 5 days. Radiation will be given between the first and second doses of ipilimumab plus nivolumab.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with a partial or complete response	The response rate of combined ipilimumab and nivolumab plus STR will be determined using irRECIST criteria.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	PFS will be determined from the onset of treatment to the time of documented disease progression.	2 years

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: Bristol-Myers Squibb
• Investigators: Principal Investigator: Michael Lilly, MD, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2018
• Primary Completion (Actual): April 1, 2018
• Study Completion (Actual): April 1, 2018

Study Registration Dates

• First Submitted: May 4, 2017
• First Submitted That Met QC Criteria: May 9, 2017
• First Posted (Actual): May 11, 2017

Study Record Updates

• Last Update Posted (Actual): June 18, 2018
• Last Update Submitted That Met QC Criteria: June 14, 2018
• Last Verified: June 1, 2018

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: 102576; CA209-927 (Other Grant/Funding Number: BMS)

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