A multicenter clinical study with Nivolumab for subjects with confirmed stage III or stage IV melanoma after treament with an Anti-CTLA-4 antibody.

Phase 1

Conditions: Histologically Confirmed Stage III (unresectable) or Stage IV Melanoma
MedDRA version: 20.0 Level: PT Classification code 10025671 Term: Malignant melanoma stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0 Level: PT Classification code 10025670 Term: Malignant melanoma stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2014-001286-28-CZ

Lead Sponsor: Bristol-Myers Squibb International Corporation

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 920

Inclusion Criteria

1. Signed Written Informed Consent
a) Patients 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 patient care.
b) Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study.
2. Target Population
a) Patients with progression after prior treatment containing an anti-CTLA-4 monoclonal antibody (Cohorts 1 and 2):
i) Patients with histologically confirmed malignant melanoma
ii) Eastern Cooperative Oncology Group (ECOG) PS:
(1) PS 0 to 1 (Cohort 1)
(2) PS 2 (Cohort 2; a minimum of 50 patients and a maximum of 185; clinical risk benefit ratio of Cohort 2 will be monitored by the Scientific Steering Committee)
iii) Previously treated unresectable stage III or stage IV melanoma as per the American Joint Committee on Cancer 2010 Guidelines36 regardless of BRAF mutation status
iv) Patients must have experienced disease progression or recurrence after prior treatment containing an anti-CTLA-4 monoclonal antibody
v) Prior treatment with chemotherapy, interferon (adjuvant setting), IL-2, BRAF/MEK inhibitors for patients with known BRAF mutations, MEK inhibitors for NRAS mutations, and cKIT inhibitor patients with known cKIT mutations are allowed
vi) Patients with CNS metastases:
(1) Patients are eligible if CNS metastases are treated and patients 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, patients must be either off orticosteroids or on a stable or decreasing dose 10 mg daily prednisone (or equivalent) OR
(2) Patients are eligible if they have previously untreated CNS metastases and are
neurologically asymptomatic. In addition, patients must be either off corticosteroids or on a stable or decreasing dose of 10 mg daily prednisone (or equivalent) OR
(3) Patients with additional leptomeningeal metastases are eligible if they are treated and neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrollment and have a life expectancy of at least 3 months. In addition, patients must be either off corticosteroids or on a
stable or decrease dose 10 mg daily prednisone (or equivalent)
vii)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 have been stabilized
viii) Prior palliative radiotherapy must have been completed at least 2 weeks prior to study drug administration
ix) Prior targeted therapy must have been completed at least 2 weeks prior to study
drug administration
x) Prior anti-CTLA-4 therapy must have been completed at least 4 weeks before study drug administration
xi) Prior radiotherapy o

Exclusion Criteria

1. Target Disease Exceptions
a) As of Amendment 02, this criterion is no longer applicable.
b) Patients with untreated, symptomatic CNS metastases are excluded
2. Medical History and Concurrent Diseases
a) As of Amendment 03, this criterion is not applicable.
b) Patients 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) Patients 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 patient to receive protocol therapy
e) Any treatment in a BMS-sponsored, interventional nivolumab trial or 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) Positive test for HIV
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) As of Amendment 02, this criterion is no longer applicable.
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
c) Women treated with ORAL hormone replacement therapy (HRT) are to
be excluded
unless the oral replacement therapy was stopped by investigator's
discretion at least 4
weeks prior to screening and was changed to other contraception
method.
6. As of Amendment 02, this criterion is no longer applicable
7. Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated
b) Subjects who are compulsorily detained for treatment of either a
psychiatric or physical (eg, infectious disease) illness
Eligibility criteria for this study have been carefully considered to ensure
the saf

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

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