Description:
The purpose of this study is to test the effectiveness, safety, and tolerability of the drugs
nivolumab plus ipilimumab with or without the addition of stereotactic body radiation therapy
(SBRT). Nivolumab is an antibody (a type of human protein) that is being tested to see if it
will stimulate the body's immune system to work against tumor cells. This study will test an
investigational use of nivolumab.
Title
- Brief Title: Randomized Study of Nivolumab+Ipilimumab+/- SBRT for Metastatic Merkel Cell Carcinoma
- Official Title: A Phase 2, Randomized, Multi-institutional Study of Nivolumab and Ipilimumab Versus Nivolumab, Ipilimumab and Stereotactic Body Radiation Therapy for Metastatic Merkel Cell Carcinoma
Clinical Trial IDs
- ORG STUDY ID:
MCC-18786
- SECONDARY ID:
CA209-737
- NCT ID:
NCT03071406
Conditions
- Merkel Cell Carcinoma
- Skin Cancer
Interventions
Drug | Synonyms | Arms |
---|
Nivolumab | OPDIVO | Arm A: Nivolumab + Ipilimumab |
Ipilimumab | YERVOY | Arm A: Nivolumab + Ipilimumab |
Purpose
The purpose of this study is to test the effectiveness, safety, and tolerability of the drugs
nivolumab plus ipilimumab with or without the addition of stereotactic body radiation therapy
(SBRT). Nivolumab is an antibody (a type of human protein) that is being tested to see if it
will stimulate the body's immune system to work against tumor cells. This study will test an
investigational use of nivolumab.
Trial Arms
Name | Type | Description | Interventions |
---|
Arm A: Nivolumab + Ipilimumab | Active Comparator | Nivolumab every 2 weeks and Ipilimumab every 6 weeks until progression or unacceptable toxicity. | |
Arm B: Nivolumab + Ipilimumab + SBRT | Active Comparator | Nivolumab every 2 weeks and Ipilimumab every 6 weeks until progression or unacceptable toxicity. Stereotactic Body Radiation Therapy (SBRT) to be given at the start of week 2. | |
Eligibility Criteria
Inclusion Criteria:
- At least 18 years of age
- Eastern Cooperative Oncology Group (ECOG) Performance Status less than 2
- Active disease measurable by CT or MRI
- Prior chemotherapy or immunotherapy will be allowed if new or persistent measurable
site(s) of disease are present.
- Prior radiation therapy will be allowed if there is active measurable disease burden.
- Must be either recurrent, unresectable or Stage IV American Joint Committee on Cancer
(AJCC) (7th edition) and have histologically confirmed Merkel cell carcinoma with at
least 2 distinct lesions in order to be eligible.
- Must have at least 2 distinct lesions as documented by a complete physical examination
and imaging studies within 4 weeks prior to randomization. Imaging studies must
include a diagnostic CT scan of the involved disease sites and all known sites of
resected disease and brain magnetic resonance (MRI) or CT (brain CT allowable if MRI
is contraindicated or if there is no known history of resected brain lesions).
- Tumor tissue from the core biopsy or resected site of disease must be provided for
biomarker analyses.
Exclusion Criteria:
- History of Grade 3 toxicity or use of infliximab with prior immunotherapy
- Patients with active brain metastasis.
- Active, known, or suspected autoimmune disease. Potential participants with type I
diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only
requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or
alopecia) not requiring systemic treatment are permitted to enroll.
- Patients with prior history of non-Merkel cell carcinoma malignancies are excluded
except adequately treated basal cell, squamous cell skin cancer, chronic lymphocytic
leukemia or other indolent diseases not requiring therapy; adequately treated, with
curative intent, cancer from which the patient is currently in complete remission per
investigator's judgment; or patients with history of breast cancer and no evidence of
disease on hormonal therapy to prevent recurrence and patients with prostate cancer on
adjuvant hormonal therapy with undetectable PSA are eligible.
- A condition requiring systemic treatment with either corticosteroids (> 10 mg daily
prednisone equivalent) or other immunosuppressive medications within 14 days of
randomization. Inhaled or topical steroids are permitted in the absence of active
autoimmune disease.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Overall Response Rate |
Time Frame: | 24 weeks |
Safety Issue: | |
Description: | Objective-response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1: including Complete Response (CR) rate, Partial Response (PR) rate, and Stable Disease (SD) rate will be calculated through exact binomial distribution with a 2-sided 95% confidence interval among patients who obtain a least one dose of study drug. |
Secondary Outcome Measures
Measure: | Progression Free Survival (PFS) |
Time Frame: | 36 months |
Safety Issue: | |
Description: | Median Progression Free Survival with 95% Confidence Interval. Progression is defined as progressive tumor lesions per immune-related Response Evaluation in Solid Tumors (irRECIST) definition, or appearance of one or more new Merkel cell carcinoma lesions, which can be local or distant in location from the irradiated lesions. |
Measure: | Overall Survival (OS) |
Time Frame: | 24 months |
Safety Issue: | |
Description: | Median Overall Survival with 95% Confidence Interval. The length of time from the start of treatment until death from any cause. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | H. Lee Moffitt Cancer Center and Research Institute |
Trial Keywords
- Merkel cell carcinoma (MCC)
- Metastatic
- Metastasis
- Stereotactic body radiation therapy (SBRT)
- Immunology
- Antibody
- Nivolumab
- Ipilimumab
- Metastatic skin cancer
- Cutaneous
Last Updated
June 14, 2021