A multicenter clinical study with Nivolumab for subjects with confirmed stage III or stage IV melanoma post treament with an Anti-CTLA-4 antibody.
- Conditions
- Histologically Confirmed Stage III (unresectable) or Stage IV MelanomaMedDRA version: 17.0Level: PTClassification code 10025671Term: Malignant melanoma stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 17.0Level: PTClassification code 10025670Term: Malignant melanoma stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-001286-28-IT
- Lead Sponsor
- Bristol-Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 1800
a) Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal subject care.
b) Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study.
2. Target Population
a) Subjects with histologically confirmed malignant melanoma
b) Eastern Cooperative Oncology Group (ECOG) Performance Status:
i) PS 0 to 1 (Cohort 1)
ii) PS 2 (Cohort 2; maximum of 300; clinical risk benefit ratio of Cohort 2 will be
monitored by the Scientific Steering Committee and evaluated after treatment of n = 50 for at least 2 months)
c) Previously treated unresectable stage III or stage IV melanoma as per the American Joint Committee on Cancer 2010 Guidelines 30 regardless of BRAF mutation status
d) Subjects must have experienced evaluable RECIST 1.1-defined evaluable disease progression
e) Prior treatment with chemotherapy, interferon (adjuvant setting), IL-2, BRAF/MEK inhibitors for subjects with known BRAF mutations, MEK inhibitors for NRAS mutations, and cKIT inhibitor subjects with known cKIT mutations are allowed
f) Subjects are eligible if CNS metastases are treated and subjected are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrollment. In addition, subjects must be either off corticosteroids or on a stable or decreasing dose of =10 mg daily prednisone (or equivalent)
g) Prior chemotherapy or immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer) must have been completed at least 4 weeks before study drug administration, and all adverse events have either returned to baseline or stabilized
h) Prior palliative radiotherapy must have been completed at least 2 weeks prior to study drug administration
i) Prior targeted therapy must have been completed at least 2 weeks prior to study drug administration
j) Prior anti-CTLA-4 therapy must have been completed at least 6 weeks before study drug administration
k) Prior radiotherapy or radiosurgery must have be completed at least 2 weeks prior to the first dose of study drug
l) Primary uveal/ocular and mucosal melanoma are allowed
m) Screening laboratory values must meet the following criteria prior to commencement of treatment:
i) WBCs = 2000/µL
ii) Neutrophils =1500/µL
iii) Platelets = 100 x 10³/µL
iv) Hemoglobin = 9.0 g/dL
v) Serum creatinine of = 1.5 X ULN or creatinine clearance > 40 mL/minute (using Cockcroft/Gault formula)
(1) Female CrCl= [(140- age in years) x weight in kg x 0.85) ÷(72 x serum creatinine in mg/ dL)]
(2) Male CrCl= [(140- age in years) x weight in kg x 1.00) ÷(72 x serum creatinine in mg/ dL)]
vi) AST = 3 X ULN
vii)ALT = 3 X ULN
viii) Total bilirubin = 1.5x ULN (except patients with Gilbert Syndrome who must have total bilirubin < 3.0 mg/dL)
n) Subject Re-enrollment: This study does not permit the re-enrollment of a subject that has discontinued the study as a pre-treatment failure.
3. Age and Reproductive Status
a) Men and women, aged =18 years
b) Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug.
c) Women must not be breastf
1. Target Disease Exceptions
a) Leptomeningeal metastases are excluded
b) Subjects with untreated, active CNS metastases are excluded
2. Medical History and Concurrent Diseases
a) Subjects with active, known, or suspected autoimmune disease. Subjects with Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
b) Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalent are permitted in the absence of active
autoimmune disease.
c) Subjects with previous malignancies (except non-melanoma skin cancers, in situ bladder cancer, gastric or colon cancers, cervical cancers/dysplasia or breast carcinoma in situ) are excluded unless a complete remission was achieved at least 2 years prior to study entry and no additional therapy is required or anticipated to be required during the study period
d) Any serious or uncontrolled medical disorder or active infection that, in the opinion of the investigator, may increase the risk associated with study participation, study drug administration, or would impair the ability of the subject to receive protocol therapy
e) Any treatment in a nivolumab trial or treatment in an ipilimumab trial
f) Known drug or alcohol abuse
3. Physical and Laboratory Test Findings
a) Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
b) Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
4. Allergies and Adverse Drug Reaction
a) History of severe hypersensitivity reactions to other monoclonal antibodies
b) History of allergy or intolerance (unacceptable adverse event) to study drug components or Polysorbate-80-containing infusions.
c) Subjects with a known history of the following anti-CTLA-4 therapy related adverse reactions based on the CTCAE v4.0 criteria:
i. Grade = 3 anti-CTLA-4 therapy-related adverse reaction except resolved nausea, fatigue, or endocrinopathies where clinical symptoms were able to be controlled with appropriate hormone replacement therapy
ii. Any = Grade 2 eye pain or reduction of visual acuity that did not respond to
topical therapy and did not improve to = Grade 1 severity within 2 weeks of
starting topical therapy or required systemic treatment
iii. Any = Grade 3 sensory neurologic toxicity
iv. Any Grade 4 laboratory abnormalities, except AST, ALT, or T. bilirubin:
a) AST or ALT > 10 x ULN
b) T. bilirubin > 5 x ULN
v. Subjects who required infliximab or other immune suppressants including
mycophenolic acid for management of drug-related toxicities
vi. Any other anti-CTLA-4 therapy-related adverse event requiring permanent
discontinuation of anti-CTLA-4
vii. History of Grade = 3 neurologic toxicity
viii. History of Grade = allergy to study drug components
5. Sex and Reproductive Status
a) WOCBP who are pregnant or breastfeeding
b) Women with a positive pregnancy test at enrollment or prior to administration of study medication
6. Prohibited Treatments and/or Restricted Therapies
a) The following
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method