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

NCT ID: NCT03149159

Last Updated: 2018-06-18

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-01
• Study Completion Date: 2018-04-01

Brief Summary

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.

Conditions

Clear Cell Renal Cell Carcinoma; Metastatic Renal Cell Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Nivolumab + Ipilimumab + SRT

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

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.

Ipilimumab

Intervention Type: DRUG

Ipilimumab will be given at a dose of 1mg/kg every 21 days for up to 12 weeks.

Steriotactic radiation therapy

Intervention Type: RADIATION

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.

Interventions

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.

Intervention Type: DRUG

Ipilimumab

Ipilimumab will be given at a dose of 1mg/kg every 21 days for up to 12 weeks.

Intervention Type: DRUG

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.

Intervention Type: RADIATION

Other Intervention Names

opdivo

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Medical University of South Carolina

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Lilly, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

Locations

Medical University of South Carolina

Charleston, South Carolina, United States

Countries

United States

Other Identifiers

CA209-927

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

102576

Identifier Type: -

Identifier Source: org_study_id