NCT02320058CompletedPhase 2
A Multi-Center Phase 2 Open-Label Study to Evaluate Safety and Efficacy in Subjects With Melanoma Metastatic to the Brain Treated With Nivolumab in Combination With Ipilimumab Followed by Nivolumab Monotherapy
Bristol-Myers Squibb36 sites in 1 country119 target enrollmentStarted: March 5, 2015Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Enrollment
- 119
- Locations
- 36
- Primary Endpoint
- Intracranial Clinical Benefit Rate (CBR)
Study Overview
Brief Summary
This is a study of Nivolumab combined with Ipilimumab followed by Nivolumab by itself for the treatment of patients with Melanoma that has spread to the brain. Patients with histologically confirmed Malignant Melanoma and asymptomatic brain metastases are eligible for the study.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Target Population
- •Histologically confirmed malignant melanoma with measurable metastases in the brain. Both asymptomatic and symptomatic patients.
- •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.
- •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
- •Must have tumor tissue available for biomarker analysis. Biopsy should be excisional, incisional, punch, or core needle
- •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
- •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.
- •Allowable prior therapy:
- •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
- •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
- •Steroids for physiological replacement are allowed.
- •Cohort A (asymptomatic): ECOG performance status ≤1 Cohort B (symptomatic): ECOG performance status ≤2
Exclusion Criteria
- •Target Disease Exceptions
- •History of known leptomeningeal involvement (lumbar puncture not required)
- •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)
- •Brain lesions >3 lesions which were previously treated with SRT
- •Brain lesion size > 3cm
- •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.
- •Physical and Laboratory Test Findings
- •Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
- •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
- •Allergies and Adverse Drug Reaction
- •a) History of allergy to study drug components b) History of severe hypersensitivity reaction to any monoclonal antibody
- •Other Exclusion Criteria
- •Prisoners or subjects who are involuntarily incarcerated
- •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
- •Other protocol defined inclusion/exclusion criteria could apply
Arms & Interventions
Nivolumab and Ipilimumab
Experimental
Induction Phase: Nivolumab + Ipilimumab infusion intravenously
Maintenance Phase: Nivolumab infusion intravenously
Intervention: Ipilimumab (Drug)
Nivolumab and Ipilimumab
Experimental
Induction Phase: Nivolumab + Ipilimumab infusion intravenously
Maintenance Phase: Nivolumab infusion intravenously
Intervention: Nivolumab (Drug)
Outcomes
Primary Outcomes
Intracranial Clinical Benefit Rate (CBR)
Time Frame: Up to 66 months
Intracranial Clinical Benefit Rate (CBR) is defined as the percentage of all treated participants whose best overall response is either a complete response (CR) or partial response (PR) or whose best overall response was Stable Disease (SD) with duration of \>6 months, as determined by modified RECIST 1.1 criteria for index intracranial lesions based on investigator review.
Secondary Outcomes
- Intracranial Objective Response Rate (ORR)(Up to 66 months)
- Global Clinical Benefit Rate (CBR)(Up to 66 months)
- Global Progression Free Survival (PFS)(Up to 66 months)
- Number of Participants Deaths(Up to 66 months)
- Number of Participants With Laboratory Abnormalities in Specific Liver Tests(From first dose to 30 days post last dose (Up to 66 months))
- Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests(From first dose to 30 days post last dose (Up to 66 months))
- Intracranial Progression Free Survival (PFS)(Up to 66 months)
- Extracranial Clinical Benefit Rate (CBR)(Up to 66 months)
- Extracranial Objective Response Rate (ORR)(Up to 66 months)
- Extracranial Progression Free Survival (PFS)(Up to 66 months)
- Global Objective Response Rate (ORR)(Up to 66 months)
- Number of Participants With Adverse Events (AEs)(From first dose to 30 days post last dose (Up to 66 months))
- Overall Survival (OS)(Up to 66 months)
Investigators
Study Sites (36)
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