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

Metastatic Renal Cell Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03149159
• Other study ID #: 102576
• Secondary ID: CA209-927
• Status: Withdrawn
• Phase: Phase 2
• Start date: April 1, 2018
• Est. completion date: April 1, 2018

Study information

• Verified date: June 2018
• Source: Medical University of South Carolina
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: April 1, 2018
• Est. primary completion date: April 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Clear Cell Renal Cell Carcinoma
• Metastatic Renal Cell Carcinoma

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Medical University of South Carolina	Charleston	South Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Medical University of South Carolina	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Progression free survival (PFS)	PFS will be determined from the onset of treatment to the time of documented disease progression.	2 years