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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03071406
Recruitment Status : Recruiting
First Posted : March 6, 2017
Last Update Posted : August 13, 2020
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Merkel Cell Carcinoma Skin Cancer Drug: Nivolumab Drug: Ipilimumab Radiation: Stereotactic Body Radiation Therapy (SBRT) Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Treatment
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
Actual Study Start Date : March 3, 2017
Estimated Primary Completion Date : July 2023
Estimated Study Completion Date : July 2023


Arm Intervention/treatment
Active Comparator: Arm A: Nivolumab + Ipilimumab
Nivolumab every 2 weeks and Ipilimumab every 6 weeks until progression or unacceptable toxicity.
Drug: Nivolumab
Nivolumab 240 mg/dose intravenously (IV) every 2 (q2) weeks.
Other Name: OPDIVO

Drug: Ipilimumab
Ipilimumab 1 mg/kg/dose IV q6 weeks.
Other Name: YERVOY

Active Comparator: 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.
Drug: Nivolumab
Nivolumab 240 mg/dose intravenously (IV) every 2 (q2) weeks.
Other Name: OPDIVO

Drug: Ipilimumab
Ipilimumab 1 mg/kg/dose IV q6 weeks.
Other Name: YERVOY

Radiation: Stereotactic Body Radiation Therapy (SBRT)
Stereotactic Body Radiation Therapy 24Gy in 3 fractions.
Other Name: SBRT




Primary Outcome Measures :
  1. Overall Response Rate [ Time Frame: 24 weeks ]
    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 :
  1. Progression Free Survival (PFS) [ Time Frame: 36 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.

  2. Overall Survival (OS) [ Time Frame: 24 months ]
    Median Overall Survival with 95% Confidence Interval. The length of time from the start of treatment until death from any cause.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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 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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03071406


Contacts
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Contact: Mia Aoki 813-745-4377 Mia.Aoki@moffitt.org
Contact: Sungjune Kim 813-745-7898 sungjune.kim@moffitt.org

Locations
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United States, Florida
H. Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Mia Aoki    813-745-4377    Mia.Aoki@moffitt.org   
Contact: Sungjune Kim, M.D., Ph.D.    813-745-7898    sungjune.kim@moffitt.org   
Principal Investigator: Sungjune Kim, M.D., Ph.D.         
Sub-Investigator: Jimmy Caudell, M.D.         
Sub-Investigator: Nikhil Khushalani, M.D.         
Sub-Investigator: Jane Messina, M.D.         
Sub-Investigator: Trevor Rose, M.D.         
Sub-Investigator: Louis Harrison, M.D.         
Sub-Investigator: Joseph Markowitz, M.D., Ph.D.         
Sub-Investigator: Andrew Brohl, M.D.         
Sub-Investigator: Zeynep Eroglu, M.D.         
Sub-Investigator: Evan Wuthrick, M.D.         
United States, Ohio
Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Lauren Kulesza       lauren.kulesza@osumc.edu   
Principal Investigator: Dukagjin Blakaj, MD         
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Bristol-Myers Squibb
Investigators
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Principal Investigator: Sungjune Kim, M.D., Ph.D. H. Lee Moffitt Cancer Center and Research Institute
Additional Information:
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Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT03071406    
Other Study ID Numbers: MCC-18786
CA209-737 ( Other Identifier: Bristol-Myers Squibb )
First Posted: March 6, 2017    Key Record Dates
Last Update Posted: August 13, 2020
Last Verified: August 2020

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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
Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
Merkel cell carcinoma (MCC)
Metastatic
Metastasis
Stereotactic body radiation therapy (SBRT)
Immunology
Antibody
Nivolumab
Ipilimumab
Metastatic skin cancer
Cutaneous
Additional relevant MeSH terms:
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Carcinoma, Merkel Cell
Carcinoma
Skin Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Skin Diseases
Polyomavirus Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Carcinoma, Neuroendocrine
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Adenocarcinoma
Neoplasms, Nerve Tissue
Nivolumab
Ipilimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents