Randomized Study of Nivolumab+Ipilimumab+/- SBRT for Metastatic Merkel Cell Carcinoma
Primary Purpose
Merkel Cell Carcinoma, Skin Cancer
Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Nivolumab
Ipilimumab
Stereotactic Body Radiation Therapy (SBRT)
Sponsored by
About this trial
This is an interventional treatment trial for Merkel Cell Carcinoma focused on measuring Merkel cell carcinoma (MCC), Metastatic, Metastasis, Stereotactic body radiation therapy (SBRT), Immunology, Antibody, Nivolumab, Ipilimumab, Metastatic skin cancer, Cutaneous
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, 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.
Sites / Locations
- H. Lee Moffitt Cancer Center and Research Institute
- Ohio State University Comprehensive Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Arm A: Nivolumab + Ipilimumab
Arm B: Nivolumab + Ipilimumab + SBRT
Arm Description
Nivolumab every 2 weeks and Ipilimumab every 6 weeks until progression or unacceptable toxicity.
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.
Outcomes
Primary Outcome Measures
Best Overall Response
Overall response according to Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) including Complete Response (CR) + Partial Response (PR).
Secondary Outcome Measures
Progression Free Survival (PFS)
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.
Overall Survival (OS)
Median Overall Survival with 95% Confidence Interval. The length of time from the start of treatment until death from any cause.
Full Information
NCT ID
NCT03071406
First Posted
March 1, 2017
Last Updated
September 20, 2023
Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
Bristol-Myers Squibb
1. Study Identification
Unique Protocol Identification Number
NCT03071406
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 14, 2017 (Actual)
Primary Completion Date
April 6, 2022 (Actual)
Study Completion Date
July 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
Bristol-Myers Squibb
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Participants are randomly assigned in a 1:1 ratio to Arm A (nivolumab + ipilimumab), or Arm B (nivolumab + ipilimumab + SBRT).
Masking
None (Open Label)
Allocation
Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A: Nivolumab + Ipilimumab
Arm Type
Active Comparator
Arm Description
Nivolumab every 2 weeks and Ipilimumab every 6 weeks until progression or unacceptable toxicity.
Arm Title
Arm B: Nivolumab + Ipilimumab + SBRT
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
OPDIVO
Intervention Description
Nivolumab 240 mg/dose intravenously (IV) every 2 (q2) weeks.
Intervention Type
Drug
Intervention Name(s)
Ipilimumab
Other Intervention Name(s)
YERVOY
Intervention Description
Ipilimumab 1 mg/kg/dose IV q6 weeks.
Intervention Type
Radiation
Intervention Name(s)
Stereotactic Body Radiation Therapy (SBRT)
Other Intervention Name(s)
SBRT
Intervention Description
Stereotactic Body Radiation Therapy 24Gy in 3 fractions.
Primary Outcome Measure Information:
Title
Best Overall Response
Description
Overall response according to Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) including Complete Response (CR) + Partial Response (PR).
Time Frame
Up to 18 months
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS)
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.
Time Frame
up to 28 months
Title
Overall Survival (OS)
Description
Median Overall Survival with 95% Confidence Interval. The length of time from the start of treatment until death from any cause.
Time Frame
Up to 30 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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, 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Evan Wuthrick, M.D
Organizational Affiliation
H. Lee Moffitt Cancer Center and Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
H. Lee Moffitt Cancer Center and Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Ohio State University Comprehensive Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
36108657
Citation
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.
Results Reference
background
Links:
URL
https://moffitt.org/clinical-trials-research/
Description
Moffitt Cancer Center Clinical Trials website
Learn more about this trial
Randomized Study of Nivolumab+Ipilimumab+/- SBRT for Metastatic Merkel Cell Carcinoma
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