An Investigational Immuno-therapy Study to Evaluate Safety and Effectiveness in Patients With Melanoma That Has Spread to the Brain, Treated With Nivolumab in Combination With Ipilimumab, Followed by Nivolumab by Itself
NCT ID: NCT02320058
Last Updated: 2021-10-05
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
119 participants
INTERVENTIONAL
2015-03-05
2020-09-08
Brief Summary
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Detailed Description
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Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Nivolumab and Ipilimumab
Induction Phase: Nivolumab + Ipilimumab infusion intravenously
Maintenance Phase: Nivolumab infusion intravenously
Ipilimumab
Nivolumab
Interventions
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Ipilimumab
Nivolumab
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
1. Histologically confirmed malignant melanoma with measurable metastases in the brain. Both asymptomatic and symptomatic patients.
2. Cohort A (asymptomatic patients): At least 1 measurable brain metastasis ≥ 0.5 cm in and ≤ 3 cm in longest diameter that has not been previously irradiated. No clinical requirement for local intervention (surgery, radiosurgery, corticosteroid therapy) or other systemic therapy
Cohort B (symptomatic patients): Subjects with neurologic signs and symptoms related to metastatic brain lesions are eligibile. Subjects must have at least 1 measurable brain metastasis ≥ 0.5 cm in and ≤ 3 cm in longest diameter that has not been previously irradiated. No immediate requirement (within 3 weeks prior to first treatment) for local intervention (surgery, radiosurgery, corticosteroid therapy). Steroid use is permitted as defined in the protocol.
3. Prior stereotactic radiotherapy (SRT) and prior excision of up to 3 melanoma brain metastases is permitted if there has been complete recovery, with no neurologic sequelae, and measurable lesions remain. Growth or change in a lesion previously irradiated will not be considered measurable. Regrowth in cavity of previously excised lesion will not be considered measurable. lesions or prior excision must have occurred ≥ 3 weeks before the start of dosing for this study
4. Must have tumor tissue available for biomarker analysis. Biopsy should be excisional, incisional, punch, or core needle
5. Cohort A (asymptomatic): Subjects must be free of neurologic signs and symptoms related to metastatic brain lesions and must not have required or received systemic corticosteroid therapy within 10 days prior to first treatment.
Cohort B (symptomatic): Subjects with neurologic signs and symptoms related to metastatic brain lesions are eligible per Amendment 02. Subjects with neurologic signs and symptoms may be treated with a total daily dose of no more than 4 mg of dexamethasone that is stable or tapering for 10 days prior to first treatment. Subjects with neurologic signs and symptoms who are not being treated with steroids are eligible for Cohort B and should have no experience of seizure within 10 days prior to first treatment.
6. Allowable prior therapy:
1. Approved adjuvant therapies, which may include molecularly-targeted agents, IFN α, and ipilimumab. Patients who received ipilimumab as adjuvant therapy must have a 6 month washout before receiving any dosing on this study
2. For advanced disease, interleukin-2 at any dose and/or IFN-α (any formulation, no washout required); MEK and BRAF inhibitors: washout for at least 4 weeks prior to the start of dosing in this study
3. Steroids for physiological replacement are allowed.
7. Cohort A (asymptomatic): ECOG performance status ≤1 Cohort B (symptomatic): ECOG performance status ≤2
Exclusion Criteria
1. History of known leptomeningeal involvement (lumbar puncture not required)
2. Previous stereotactic or highly conformal radiotherapy within 3 weeks before the start of dosing for this study. Note the stereotactic radiotherapy field must not have included the brain index lesion(s)
3. Brain lesions \>3 lesions which were previously treated with SRT
4. Brain lesion size \> 3cm 3. Medical History and Concurrent Diseases
a) History of whole brain irradiation b) Subjects with an active, known or suspected autoimmune disease c) Subjects with major medical, neurologic or psychiatric condition who are judged as unable to fully comply with study therapy or assessments should not be enrolled d) Any concurrent malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix. For any prior invasive malignancy, at least 5 years must have elapsed since curative therapy and patients must have no residual sequelae of prior therapy e) Cohort A (asymptomatic): The use of corticosteroids is not allowed within 10 days prior to first treatment (based upon 5 times the expected half life of dexamethasone) except patients who are taking steroids for physiological replacement. If alternative corticosteroid therapy has been used, consultation with the sponsor Medical Monitor is required to determine the washout period prior to initiating study treatment Cohort B (symptomatic): Subjects with neurologic sign and symptoms related to brain metastases who are being treated with a total daily dose of higher than 4 mg dexamethasone or equivalent within 10 prior to the start of treatment with study drug are excluded.
4\. Physical and Laboratory Test Findings
1. Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
2. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) even if fully immunocompetent on ART-due to the unknown effects of HIV on the immune response to combined nivolumab plus ipilimumab or the unique toxicity spectrum of these drugs in patients with HIV
5\. Allergies and Adverse Drug Reaction
a) History of allergy to study drug components b) History of severe hypersensitivity reaction to any monoclonal antibody
1. Prisoners or subjects who are involuntarily incarcerated
2. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness Eligibility criteria for this study have been carefully considered to ensure the safety of the study subjects and that the results of the study can be used. It is imperative that subjects fully meet all eligibility criteria
18 Years
ALL
No
Sponsors
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Bristol-Myers Squibb
INDUSTRY
Responsible Party
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Principal Investigators
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Bristol-Myers Squibb
Role: STUDY_DIRECTOR
Bristol-Myers Squibb
Locations
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City of Hope
Duarte, California, United States
Angeles Clinic and Research Institute
Los Angeles, California, United States
UCLA Medical Hematology and Oncology
Los Angeles, California, United States
Stanford University
Palo Alto, California, United States
The California Pacific Medical Research Institute
San Francisco, California, United States
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States
University of Colorado - Cancer Center - PPDS
Aurora, Colorado, United States
Washington Cancer Inst at MedStar Washington Hospital Ctr
Washington D.C., District of Columbia, United States
Weinberg Cancer Institute At Franklin Square
Washington D.C., District of Columbia, United States
Georgetown University Medical Center
Washington D.C., District of Columbia, United States
Mount Sinai Medical Center
Miami Beach, Florida, United States
H Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States
The Cleveland Clinic Foundation
Weston, Florida, United States
Winship Cancer Institute, Emory University
Atlanta, Georgia, United States
University of Chicago
Chicago, Illinois, United States
Loyola University Medical Center
Maywood, Illinois, United States
Dana Farber Cancer Institute.
Boston, Massachusetts, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States
Karmanos Cancer Institute
Detroit, Michigan, United States
Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
NYU Langone Medical Center
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
Duke University Medical Center
Durham, North Carolina, United States
Case School of Medicine University Hospitals of Cleveland
Cleveland, Ohio, United States
Lehigh Valley Health Network
Allentown, Pennsylvania, United States
St Luke's Health Network
Easton, Pennsylvania, United States
Abramson Cancer Center of The University of Pennsylvania
Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
MD Anderson Cancer Center
Houston, Texas, United States
University of Utah - Huntsman Cancer Institute - PPDS
Salt Lake City, Utah, United States
Inova Melanoma and Skin Cancer Center
Fairfax, Virginia, United States
Countries
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References
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Huang RY, Youssef G, Nelson T, Wen PY, Forsyth P, Hodi FS, Margolin K, Algazi AP, Hamid O, Lao CD, Ernstoff MS, Moschos SJ, Atkins MB, Postow MA, Reardon DA, Grootendorst DJ, Leung D, Askelson M, Ritchings C, Tawbi HA. Comparative Analysis of Intracranial Response Assessment Criteria in Patients With Melanoma Brain Metastases Treated With Combination Nivolumab + Ipilimumab in CheckMate 204. J Clin Oncol. 2025 Apr;43(10):1210-1218. doi: 10.1200/JCO.24.00953. Epub 2025 Jan 3.
Johannet P, Simons M, Qian Y, Azmy N, Mehnert JM, Weber JS, Zhong J, Osman I. Risk and tropism of central nervous system (CNS) metastases in patients with stage II and III cutaneous melanoma. Cancer. 2022 Oct;128(20):3620-3629. doi: 10.1002/cncr.34435. Epub 2022 Aug 25.
Tawbi HA, Forsyth PA, Hodi FS, Algazi AP, Hamid O, Lao CD, Moschos SJ, Atkins MB, Lewis K, Postow MA, Thomas RP, Glaspy J, Jang S, Khushalani NI, Pavlick AC, Ernstoff MS, Reardon DA, Kudchadkar R, Tarhini A, Chung C, Ritchings C, Durani P, Askelson M, Puzanov I, Margolin KA. Long-term outcomes of patients with active melanoma brain metastases treated with combination nivolumab plus ipilimumab (CheckMate 204): final results of an open-label, multicentre, phase 2 study. Lancet Oncol. 2021 Dec;22(12):1692-1704. doi: 10.1016/S1470-2045(21)00545-3. Epub 2021 Nov 10.
Tawbi HA, Forsyth PA, Hodi FS, Lao CD, Moschos SJ, Hamid O, Atkins MB, Lewis K, Thomas RP, Glaspy JA, Jang S, Algazi AP, Khushalani NI, Postow MA, Pavlick AC, Ernstoff MS, Reardon DA, Puzanov I, Kudchadkar RR, Tarhini AA, Sumbul A, Rizzo JI, Margolin KA. Safety and efficacy of the combination of nivolumab plus ipilimumab in patients with melanoma and asymptomatic or symptomatic brain metastases (CheckMate 204). Neuro Oncol. 2021 Nov 2;23(11):1961-1973. doi: 10.1093/neuonc/noab094.
Tawbi HA, Forsyth PA, Algazi A, Hamid O, Hodi FS, Moschos SJ, Khushalani NI, Lewis K, Lao CD, Postow MA, Atkins MB, Ernstoff MS, Reardon DA, Puzanov I, Kudchadkar RR, Thomas RP, Tarhini A, Pavlick AC, Jiang J, Avila A, Demelo S, Margolin K. Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain. N Engl J Med. 2018 Aug 23;379(8):722-730. doi: 10.1056/NEJMoa1805453.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
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BMS Clinical Trial Information
BMS Clinical Trial Patient Recruiting
Investigator Inquiry Form
FDA Safety Alerts and Recalls
Other Identifiers
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CA209-204
Identifier Type: -
Identifier Source: org_study_id
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