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

NCT03149159 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: 102576CA209-927
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Progression free survival (PFS)

  2 years

Study Arms (1)

Nivolumab + Ipilimumab + SRT

EXPERIMENTAL

Drug: Nivolumab; Drug: Ipilimumab; Radiation: Steriotactic radiation therapy

Interventions

Nivolumab 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.

Also known as: opdivo

Nivolumab + Ipilimumab + SRT

Ipilimumab DRUG

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

Nivolumab + Ipilimumab + SRT

Steriotactic radiation therapy 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.

Nivolumab + Ipilimumab + SRT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical University of South Carolina: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Michael Lilly, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2017
• First Posted: May 11, 2017
• Study Start: April 1, 2018
• Primary Completion: April 1, 2018
• Study Completion: April 1, 2018
• Last Updated: June 18, 2018

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)