An exploratory study of the biologic effects of nivolumab and nivolumab in combination with ipilimumab treatment in subjects with advanced melanoma (unresectable or metastatic).
- Conditions
- Advanced (unresectable or metastatic) melanoma10040900
- Registration Number
- NL-OMON41223
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 10
• Men and women >= 16 years of age
• Subjects must have ECOG performance status <= 1
• Subjects with advanced melanoma (unresectable or metastatic) who have received and either progressed or discontinued on no more than 3 prior treatment regimens or have refused standard therapy for treatment of metastatic melanoma.
• Subjects enrolled to Arm A, B, D and E (Part 2, 3 and 4) must never received anti-CTLA4 therapy
• Subjects must have histologic confirmation of advanced melanoma
• Subjects must have at least one measurable lesion at baseline by CT or MRI as per RECIST 1.1 criteria
• Subjects must have at least 1 tumor site that can be biopsied at acceptable clinical risk and must consent to pre- and on-treatment tumor biopsies
• Subjects enrolled to Arms D and E (Part 4)
o Must have at least one measurable index brain metastases > 0.5 cm and not larger than 3 cm that has not been previously irradiated
o Index brain lesions must not have sequela of prior therapy that would confound attribution of tumor response including edema or hemorrhage
o Must not have neurologic symptoms secondary to metastatic lesions
o Must not have received systemic corticosteroids within 14 days prior to initiation of study therapy
• Active brain metastases within 28 days of study enrollment (Arms A and B - Part 2 & 3) within 28 days of study enrollment
• Subjects with known metastases must have a repeat imaging brain scan within 28 days of randomization/registration. If progression in prior lesion(s) or new lesion (s) is/are detected on repeat brain scan, patients are exluded from study (Arms A en B - Part 2 & 3)
• History of carcinomatous meningitis (Arms D and E - Part 4)
• Radiation within 14 days prior to initiation of study therapy, and the radiation field cannot have included the index brain lesion (Arms D and E - Part 4)
• Subjects with other concomitant malignancies, except basal cell or squamous cell skin cancers, superficial bladder cancer, or carcinoma in situ of the cervix or breast, 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
• Subjects with active autoimmune disease, a history of known or suspected autoimmune disease or a history of a syndrome requiring systemic corticosteroids (> 10 mg daily prednisone equivalent), cytotoxic therapy or immunosuppressive medications with the exception of:
o Isolated vitiligo
o Resolved childhood atopy
o The history of positive ANA titer without associated symptoms or history of symptoms of an autoimmune disorder
o Controlled thyroid disorders
• Positive tests for HIV1/2 antibody or known acquired immunodeficiency syndrome (AIDS)
• History of any hepatitis
• Prior therapy with any antibody/drug that targets the T cell coregulatory proteins, including but not limited to, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40,and anti-CD40 antibodies
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary objective relating to the pharmacodynamic activity of biomarkers<br /><br>will be measured by changes from baseline in activated and memory T cells,<br /><br>interferon inducible factors, and CD4 and CD8 T cell infiltration.</p><br>
- Secondary Outcome Measures
Name Time Method