A Multi-Center, Randomized, Double-Blind, Two-Arm, Phase III Study in Patients with Untreated Stage III (Unresectable) or IV Melanoma Receiving Dacarbazine Plus 10 mg/kg of Ipilimumab (MDX-010) vs. Dacarbazine With Placebo
- Conditions
- melanosarcomaskincancer10040900
- Registration Number
- NL-OMON34151
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 12
1) Willing and able to give written informed consent;
2) Histologic diagnosis of malignant melanoma;
3) Untreated unresectable Stage III melanoma with N3 macroscopic lymph nodes or in-transit / satellite metasteses or Stage IV melanoma (AJCC 2001) (note that prior adjuvant melanoma therapy is permitted) [i.e., IFN therapy]);
4) Measurable/evaluable disease (as per modified WHO criteria), within 28 days of first dose of study drug;
5) Life expectancy of * 16 weeks;
6) ECOG performance status of 0 or 1;
7) Have the complete set of baseline (i.e. Screening) digital images of lesions and radiographic images, including, but not limited to: brain, chest, abdomen, pelvis and bone scans. All images must be of adequate quality;
8) Required values for initial laboratory tests:
* Platelets * 75 x 103/uL
* Hemoglobin * 9 g/dL
* Creatinine * 2.5 x ULN
* AST * 3 x ULN for patients without liver metastases
* 5 x ULN for patients with liver metastases
* Bilirubin * 3 x ULN, (except patients with Gilbert*s Syndrome, who must have a
total bilirubin less than 3.0 mg/dL;
9) Negative Screening tests for HIV, HepB, and HepC. If positive results are not indicative of true active or chronic infection, the patient can enter the study after discussion and agreement between the Investigator and the CRO Medical Monitor;
10) Accessible for treatment and Follow-Up;
11) Men and women > 18 years of age (or, * 16, if allowable per local regulatory authority);WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal [defined as amenorrhea * 12 consecutive months; or women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level > 35mIU/mL]. Even women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy), should be considered to be of child bearing potential.
WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of study medication.
1) 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.
2) Women who are pregnant or breastfeeding
3) Women with a positive pregnancy test on enrollment or prior to study drug administration.
4) Sexually active fertile men whose partners are WOCBP, unless using an adequate method of birth control
5) Evidence of brain metastases on brain imaging (i.e. MRI or contrast CT);
6) Any other 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 or carcinoma in situ of the cervix;
7) Primary ocular or mucosal melanoma;
8) 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 history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus, autoimmune vasculitis [e.g., Wegener*s Granulomatosis]);
9) Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea;
10) Prior or concomitant therapy with any anti-cancer agent, immunosuppressive agents, surgery or radiotherapy (except as defined in Sections 6.2.8.3 and 6.2.8.4 of the protocol); other investigational anti-cancer therapies, or chronic use of systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses). Prior adjuvant therapy is not exclusionary;
11) Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 4 weeks prior to or after any dose of ipilimumab or dacarbazine);
12) Prior treatment with a CD137 agonist or CTLA-4 inhibitor or agonist;
13) Previous participation in another ipilimumab (MDX-010) clinical trial;
14) Treatment with other investigational products within the last 4 weeks prior to randomization into this study.
15) Prisoners or patients who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be randomized into this study.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary outcome of this study will be the comparison of the overall<br /><br>survival (OS) between the two treatment arms. </p><br>
- Secondary Outcome Measures
Name Time Method <p>The main secondary outcome will be the comparison of progression free survival<br /><br>(PFS) between the two treatment arms.<br /><br>Other secondary outcomes will be survival rate at 1 year, PFS at week 12, best<br /><br>overall response rate (BORR), disease control rate, time to best objective<br /><br>response and duration of best objective response.</p><br>