None listed
Conditions
Interventions
GROUP 1 Type of group
1) Induction phase: This group will be treated with MDX-010 (BMS-734016) 3 mg / kg in a single dose in weeks 1,4,7 and 10.
2) Maintenance Phase: Patients who meet the requirements to enter this phase, will receive MDX-010 (BMS-734016) 3 mg / kg every 12 Weeks starting in Week 24 until progression or until the toxicities require discontinuation.
Group name:GROUP 2 Type of group
1) Induction phase: This group will be treated with MDX-010 (BMS-734016) 10 mg / kg in a single dose in weeks 1,4,7 and 10.
2) Maintenance Phase: Patients who meet the requirements to enter this phase will receive MDX-010 (BMS-734016) 10 mg / kg every 12 weeks starting at Week 24 until progression or until the toxicities require discontinuation .
Sponsors
BRISTOL MYERS SQUIBB COMPANY,
Eligibility
Inclusion criteria
Inclusion criteria: a) Written informed consent, voluntarily signed and dated. It must be obtained before performing the procedures related to the protocol. b) Able to comply with visits / procedures required by the protocol. c) Life expectancy of at least 4 months. d) ECOG 0-1 performance status score. e) Histological or cytological diagnosis of non-resectable malignant melanoma of Stage III or IV. f) A resected tumor biopsy or recent center should be submitted before and after treatment for the analysis of biomarkers and predictive markers. It is preferred that the biopsies are obtained from the same organ. g) Disease susceptible of measurement. h) Values ​​adequate for initial laboratory tests. i) It must have been at least 4 weeks since the last chemotherapy, immunotherapy, hormonal therapy, radiotherapy or major surgery and the beginning of the protocol therapy. j) The toxicity related to the previous therapy must have returned to ≤ grade 1, to the baseline or be considered irreversible. k) Men and women 18 years and older. Women of childbearing age (WOCBP) should be using an adequate contraceptive method. The WOCBP must have a negative pregnancy test within 72 hours prior to the start of the study medication.
Exclusion criteria
Exclusion criteria: a) WOCBPs that are not willing or able to use an acceptable method to avoid pregnancy during the entire study period and for at least 12 weeks after the study. b) WOCBPs that use a prohibited method of contraception. c) Women who are pregnant or breastfeeding. d) Women with a positive pregnancy test at the time of enrollment or before administration of the study drug. e) Sexually active fertile men who are unwilling or unable to use a barrier contraceptive or whose partners are WOCBP who do not use a method of birth control from the moment of enrollment and for 12 weeks after participation in the study. f) Any other malignant disease that the patient has suffered for less than 5 years. g) Ocular melanoma. h) Central nervous system (CNS) metastasis untreated and active. i) Autoimmune disease. j) Any underlying medical condition, which makes the administration of the study drug dangerous or hinders the interpretation of adverse events. k) Positive screening tests for HIV, HepB and HepC. If the positive results are not indicative of true active or chronic infection, the patient can be admitted after being discussed and agreed with the BMS Medical Monitor. l) Uncontrolled or significant cardiovascular disease. m) Pre-treatment with an anti-CLTA-4 antibody. n) Use of any immunosuppressive treatment within 4 weeks prior to Day 1 of treatment. m) Exposure to any of the products under investigation within 4 weeks prior to Day 1 of the treatment. o) Drugs of which it is generally accepted that they have a risk of originating Torsade de Pointes. Patients who have discontinued any of these medications should have a drug withdrawal period of at least 5 days or at least 5 half-lives of the drug (whichever is longer) before the first dose of MDX-010 ( BMS-734016). p) Concomitant therapy with any of the following: IL-2, interferon or other anti-melanoma immunotherapy regimens that are not in the study; cytotoxic chemotherapy; immunosuppressive agents; other therapies in research or the chronic use of systemic corticosteroids. q) Concomitant chemotherapy is prohibited. r) Prisoners or patients who are required to be detained for the treatment of either a psychiatric or physical illness should not be enrolled in this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:Clinical evaluation where it will be determined: 1) Complete Response (CR); The complete disappearance of all tumor lesions for at least 4 weeks from the date of documentation of the complete response. 2) Partial Response (PR); The decrease, relative to the baseline, of 50% or more in the sum of the products of the two largest perpendicular diameters of all index injuries as determined by two observations at least 4 weeks apart. For this evaluation, images (CT, MRI) of the thorax, abdomen and pelvis will be required at each tumor evaluation visit. The CNS images should be obtained when clinically required by the appearance of relevant symptoms. In addition, visible lesions of the skin will be measured clinically using standardized photographs. Measure:Index of best objective response: it is defined as the total number of patients whose best response is CR or PR, divided by the total number of randomized patients. Timepoints:Week 24. ; Outcome name:Clinical evaluation of adverse events according to the Criteria of Common Terminology for Adverse Events v3.0 (CTCAE) of the National Cancer Institute (NCI). Physical examination and evaluation of vital signs. 12-lead EKG. Clinical laboratory tests: Panels of serum biochemistry and hematology. Measure:Safety of the treatment. Timepoints:Week 24. | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:A clinical evaluation will be performed looking for evidence of progression: a) At least 25% increase in the sum of the products of all index injuries. b) Emergence of new lesions. c) unequivocal progression of existing non-index injuries. d) Increase in pleural effusions, or other fluid collections. e) Occurrence of new pleural effusions or ascites. For the evaluation of these will be performed CT, MRI, chest X-ray and abdomen. The physical measurements of the lesions progression or the evaluation of new ones will be carried out in the weeks: Before the treatment and in the week 1, 4, 7, 10 and when it is required according to clinical decision. Measure:Index of survival without disease progression (PFS) in Week 12: Total number of patients who have survived without progression of the disease in week 12 divided by the total number of patients randomized. Timepoints:Week 24. ; Outcome name:Clinical evaluation: To assess compliance with the criteria CP, PR or disease progression and determine the time to reach these criteria or the death of the patient. To achieve these evaluations, a physical evaluation and measurement of tumor lesions by means of photographic images, CT or MRI will be necessary. Measure:1232/5000 Disease control index: Total number of patients with CR or PR or SD divided by the total number of patients randomized. Survival without Progression of Disease (PFS): Time between the date of the randomization and the date of the progression or death General Survival (OS): Time between the date of randomization and death Duration of the Best Objective Response: Time between the date of the first response (PR or CR) and the date of the progression of the disease or death. Best Objective Response Time: Time from the first dose of study therapy until the measurement criteria are met first for PR or CR. Timepoints:Week 24. ; Outcome name:DTH skin test and antibody titers. Flow | — |
Countries
Denmark, Israel, Italy, Norway, Peru, Sweden, United States
Outcome results
None listed