Randomized Study of Nivolumab+Ipilimumab+/- SBRT for Metastatic Merkel Cell Carcinoma

Phase 2

Active, not recruiting

• Conditions: Merkel Cell Carcinoma; Skin Cancer
• Interventions: Drug: Nivolumab; Drug: Ipilimumab; Radiation: Stereotactic Body Radiation Therapy (SBRT)

• Registration Number: NCT03071406
• Lead Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-03-01
• Study First Submitted QC: 2017-03-01
• Study First Posted: 2017-03-06
• Study Start: 2017-03-14
• Primary Completion: 2022-04-06
• Results First Submitted: 2023-04-03
• Results First Submitted QC: 2023-04-26
• Results First Posted: 2023-05-19
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-04
• Last Update Posted: 2025-02-20
• Study Completion: 2025-03

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• At least 18 years of age
• Eastern Cooperative Oncology Group (ECOG) Performance Status less than 2
• Active disease measurable by CT, MRI or clinical exam.
• 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 or 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm B: Nivolumab + Ipilimumab + SBRT	Stereotactic Body Radiation Therapy (SBRT)	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.
Arm B: Nivolumab + Ipilimumab + SBRT	Ipilimumab	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.
Arm A: Nivolumab + Ipilimumab	Ipilimumab	Nivolumab every 2 weeks and Ipilimumab every 6 weeks until progression or unacceptable toxicity.
Arm A: Nivolumab + Ipilimumab	Nivolumab	Nivolumab every 2 weeks and Ipilimumab every 6 weeks until progression or unacceptable toxicity.
Arm B: Nivolumab + Ipilimumab + SBRT	Nivolumab	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.

Primary Outcome Measures

Name	Time	Method
Best Overall Response	Up to 18 months	Overall response according to Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) including Complete Response (CR) + Partial Response (PR).

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Up to 30 months	Median Overall Survival with 95% Confidence Interval. The length of time from the start of treatment until death from any cause.
Progression Free Survival (PFS)	up to 28 months	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.

Trial Locations

Locations (2)

H. Lee Moffitt Cancer Center and Research Institute; 🇺🇸 Tampa, Florida, United States

Ohio State University Comprehensive Cancer Center; 🇺🇸 Columbus, Ohio, United States