Patients with Unresectable Locally Advanced or Metastatic Malignant Melanoma MedDRA version: 9.1 Level: LLT Classification code 10025670 MedDRA version: 9.1 Level: LLT Classification code 10025671
Conditions
Interventions
Product Name: ipilimumab
Product Code: BMS-734016
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: IPILIMUMAB
CAS Number: 477202-00-9
Current Sponsor code: BMS-734016
Concentration unit
Sponsors
NIBIT (NETWORK ITALIANO PER LA BIO-IMMUNOTERAPIA DEI TUMORI)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Signed Written Informed Consent a) Willing and able to give written informed consent. 2) Target Population a) Histologic diagnosis of malignant melanoma; b) Stage III (unresectable) or Stage IV melanoma; c) Maximum 1 line of chemotherapy for advanced disease allowed; d) No prior chemotherapy within 4 weeks from treatment start (6 weeks in case of nitrosourea); e) No previous systemic corticosteroid therapy within 10 days; f) Prior adjuvant treatment with IFN or other immunotherapy allowed; g) Asymptomatic brain metastases allowed; h) Measurable disease; i) Prior treatment of brain metastases. In case stereotactic radiotherapy (or surgery) was not applicable, whole brain radiotherapy should have been performed; j) Have a full set of baseline (ie, Screening) radiographic images, including, but not limited to: brain, chest, abdomen, pelvis and soft tissue and assessment of skin lesions. All images must be of adequate quality as detailed in Section 6.4; k) Life expectancy ? 16 weeks Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 4) Sex and Reproductive Status a) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the study; b) Women who are pregnant or breastfeeding; c) Women with a positive pregnancy test on enrollment or prior to investigational product administration; d) Sexually active fertile men not using effective birth control if their partners are WOCBP. 5) Target Disease Exceptions a) Any malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix; b) Primary ocular or mucosal melanoma. 6) Medical History and Concurrent Diseases a) Symptomatic brain metastases requiring immediate local intervention (radiotherapy (RT) and/or surgery); b) Autoimmune disease: Patients with a documented history of Inflammatory Bowel Disease, including ulcerative colitis and Crohn?s disease are excluded from this study as are patients with a documented history of symptomatic autoimmune disease (eg, rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus, autoimmune vasculitis [eg, Wegener?s Granulomatosis] and autoimmune hepatitis. Subjects with motor neuropathy considered of autoimmune origin (eg, Guillain-Barre Syndrom) are also excluded from this study; c) Any underlying medical condition, which in the opinion of the investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea. 7) Prohibited Treatments and/or Therapies a) Concomitant therapy with any anti-cancer agent; immunosuppressive agents; any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month prior to or after any dose of study drug); surgery or radiotherapy (except as described in Sections 5.5.1 and 5.5.2); other investigational anti-cancer therapies; or chronic use of systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses); b) Previous treatment with other investigational products, including cancer immunotherapy, within 30 days; c) Previous enrollment in another clinical trial or prior treatment with a CD137 agonist or anti-CTLA-4 and/or fotemustine. 8) 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the immune-response Disease Control Rate (irDCR) using the immune related (ir) tumor response criteria of the combination of ipilimumab and fotemustine in patients with unresectable locally advanced or metastic melanoma;Secondary Objective: ? To assess safety, tolerability and feasibility of the combination ? To further describe efficacy using the following tumor response indicators (assessed using the immune-related response criteria,ir-RC) and clinical endpoints: ? Major Durable Disease Control Rate, Objective Response Rate, Duration of Response, Time to Response, and Progression-Free Survival using immune-related tumor response criteria (ie, irMDDCR, irORR, irDOR, irTTR, and irPFS); ? Brain Progression-free Survival (Brain-PFS); ? Overall Survival (OS) as summarized by Median Survival and Survival Rate at 1 and 2 years. ? To assess the pharmacodynamic effects of ipilimumab and fotemustine in combination on Absolute Lymphocyte Count (ALC) ? To assess associations between ALC and anti-tumor activity of ipilimumab and fotemustine in combination ? Translational studies;Primary end point(s): The primary endpoint is the ir-Disease Control Rate (irDCR) | — |
Countries
Italy
Outcome results
None listed