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

NCT03071406 | Active Not Recruiting Phase 2 Results FDA Drug

• 2 other identifiers: MCC-18786CA209-737
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

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.

Conditions

Merkel Cell Carcinoma; Skin Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Best Overall Response

  Overall response according to Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) including Complete Response (CR) + Partial Response (PR).

  Up to 18 months

Secondary Outcomes (2)

• Progression Free Survival (PFS)

  up to 28 months

• Overall Survival (OS)

  Up to 30 months

Study Arms (2)

Arm A: Nivolumab + Ipilimumab

ACTIVE COMPARATOR

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

Drug: Nivolumab; Drug: Ipilimumab

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.

Drug: Nivolumab; Drug: Ipilimumab; Radiation: Stereotactic Body Radiation Therapy (SBRT)

Interventions

Stereotactic Body Radiation Therapy (SBRT) RADIATION

Stereotactic Body Radiation Therapy 24Gy in 3 fractions.

Also known as: SBRT

Arm B: Nivolumab + Ipilimumab + SBRT

Ipilimumab DRUG

Ipilimumab 1 mg/kg/dose IV q6 weeks.

Also known as: YERVOY

Arm A: Nivolumab + Ipilimumab; Arm B: Nivolumab + Ipilimumab + SBRT

Nivolumab DRUG

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

Also known as: OPDIVO

Arm A: Nivolumab + Ipilimumab; Arm B: Nivolumab + Ipilimumab + SBRT

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bristol-Myers Squibb: collaborator
• H. Lee Moffitt Cancer Center and Research Institute: lead

Study Sites (2)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Publications (2)

• 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.

  PMID: 36108657 BACKGROUND

• 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.

  PMID: 39021272 DERIVED

Related Links

• Moffitt Cancer Center Clinical Trials website

MeSH Terms

Conditions

Carcinoma, Merkel Cell; Skin Neoplasms; Neoplasm Metastasis

Interventions

Nivolumab; Ipilimumab; Radiosurgery

Condition Hierarchy (Ancestors)

Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Sungjune Kim, MD, PhD
• Organization: Moffitt Cancer Center

sungjune.kim@moffitt.org

813-745-1898

Study Officials

• Evan Wuthrick, M.D

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

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

Study Record Dates

• First Submitted: March 1, 2017
• First Posted: March 6, 2017
• Study Start: March 14, 2017
• Primary Completion: April 6, 2022
• Study Completion (Estimated): September 19, 2026
• Last Updated: March 11, 2026
• Results First Posted: May 19, 2023

Record last verified: 2026-02

Locations

US (2)