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

NCT ID: NCT03071406

Last Updated: 2025-12-22

Study Results

Results available

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-03-14

Study Completion Date

2026-09-30

Brief Summary

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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

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Conditions

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Merkel Cell Carcinoma Skin Cancer

Keywords

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Merkel cell carcinoma (MCC) Metastatic Metastasis Stereotactic body radiation therapy (SBRT) Immunology Antibody Nivolumab Ipilimumab Metastatic skin cancer Cutaneous

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Participants are randomly assigned in a 1:1 ratio to Arm A (nivolumab + ipilimumab), or Arm B (nivolumab + ipilimumab + SBRT).
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A: Nivolumab + Ipilimumab

Nivolumab every 2 weeks and Ipilimumab every 6 weeks until progression or unacceptable toxicity.

Group Type ACTIVE_COMPARATOR

Nivolumab

Intervention Type DRUG

Nivolumab 240 mg/dose intravenously (IV) every 2 (q2) weeks.

Ipilimumab

Intervention Type DRUG

Ipilimumab 1 mg/kg/dose IV q6 weeks.

Arm B: Nivolumab + Ipilimumab + 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.

Group Type ACTIVE_COMPARATOR

Nivolumab

Intervention Type DRUG

Nivolumab 240 mg/dose intravenously (IV) every 2 (q2) weeks.

Ipilimumab

Intervention Type DRUG

Ipilimumab 1 mg/kg/dose IV q6 weeks.

Stereotactic Body Radiation Therapy (SBRT)

Intervention Type RADIATION

Stereotactic Body Radiation Therapy 24Gy in 3 fractions.

Interventions

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Nivolumab

Nivolumab 240 mg/dose intravenously (IV) every 2 (q2) weeks.

Intervention Type DRUG

Ipilimumab

Ipilimumab 1 mg/kg/dose IV q6 weeks.

Intervention Type DRUG

Stereotactic Body Radiation Therapy (SBRT)

Stereotactic Body Radiation Therapy 24Gy in 3 fractions.

Intervention Type RADIATION

Other Intervention Names

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OPDIVO YERVOY SBRT

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bristol-Myers Squibb

INDUSTRY

Sponsor Role collaborator

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Evan Wuthrick, M.D

Role: PRINCIPAL_INVESTIGATOR

H. Lee Moffitt Cancer Center and Research Institute

Locations

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H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Site Status

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

Countries

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United States

References

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Kim S, Wuthrick E, Blakaj D, Eroglu Z, Verschraegen C, Thapa R, Mills M, Dibs K, Liveringhouse C, Russell J, Caudell JJ, Tarhini A, Markowitz J, Kendra K, Wu R, Chen DT, Berglund A, Michael L, Aoki M, Wang MH, Hamaidi I, Cheng P, de la Iglesia J, Slebos RJ, Chung CH, Knepper TC, Moran-Segura CM, Nguyen JV, Perez BA, Rose T, Harrison L, Messina JL, Sondak VK, Tsai KY, Khushalani NI, Brohl AS. Combined nivolumab and ipilimumab with or without stereotactic body radiation therapy for advanced Merkel cell carcinoma: a randomised, open label, phase 2 trial. Lancet. 2022 Sep 24;400(10357):1008-1019. doi: 10.1016/S0140-6736(22)01659-2. Epub 2022 Sep 12.

Reference Type BACKGROUND
PMID: 36108657 (View on PubMed)

Hoogland AI, Brohl AS, Small BJ, Michael L, Wuthrick E, Eroglu Z, Blakaj D, Verschraegen C, Khushalani NI, Jim HSL, Kim S. Quality of life and patient-reported toxicities in patients with advanced Merkel cell carcinoma treated with combined nivolumab and ipilimumab with or without stereotactic body radiation therapy. Cancer Med. 2024 Jul;13(14):e7464. doi: 10.1002/cam4.7464.

Reference Type DERIVED
PMID: 39021272 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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https://moffitt.org/clinical-trials-research/

Moffitt Cancer Center Clinical Trials website

Other Identifiers

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CA209-737

Identifier Type: OTHER

Identifier Source: secondary_id

MCC-18786

Identifier Type: -

Identifier Source: org_study_id