Clinical Trials /

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

NCT03071406

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.

Related Conditions:
  • Merkel Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

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

DrugSynonymsArms
NivolumabOPDIVOArm A: Nivolumab + Ipilimumab
IpilimumabYERVOYArm 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

NameTypeDescriptionInterventions
Arm A: Nivolumab + IpilimumabActive ComparatorNivolumab every 2 weeks and Ipilimumab every 6 weeks until progression or unacceptable toxicity.
  • Nivolumab
  • Ipilimumab
Arm B: Nivolumab + Ipilimumab + SBRTActive ComparatorNivolumab 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.
  • Nivolumab
  • Ipilimumab

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 active measurable disease was not
             previously treated with radiation therapy.

          -  Must be either recurrent 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 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 previous non-Merkel cell carcinoma malignancies are excluded unless a
             complete remission was achieved at least 3 years prior to study entry and no
             additional therapy is required or anticipated to be required during the study period
             (exceptions include but are not limited to, non-melanoma/Merkel cell carcinoma skin
             cancers; in situ bladder cancer, in situ gastric cancer, in situ colon cancers; in
             situ cervical cancers/dysplasia; or breast carcinoma in situ).

          -  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

March 30, 2017