A Randomized Double-Blind Phase III Study of Ipilimumab Administered at 3 mg/kg vs at 10 mg/kg in Subjects with Previously Treated or Untreated Unresectable or Metastatic Melanoma
- Conditions
- Melanoma10040900
- Registration Number
- NL-OMON37618
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 28
Inclusion Criteria
1) Signed Written Informed Consent
a) Willing and able to give written informed consent;
2) Target Population
a) Histologically or cytologically confirmed diagnosis of malignant melanoma;
b) Previously-treated or untreated unresectable Stage III or Stage IV melanoma (AJCC 2010) (regardless of B-Raf mutation status or HLA type);
c) Prior adjuvant melanoma therapy is permitted; any number of previous treatments for melanoma are permitted except for prior B-Raf inhibitors, CTLA-4 antagonists or PD-1 antagonists, or PD-L1 or CD137 agonists;
d) Measurable/evaluable disease, within 28 days of first dose of study drug;
e) Subjects with brain metastases who are free of neurologic symptoms related to metastatic brain lesions and who do not require or receive systemic corticosteroid therapy in the 10 days prior to beginning ipilimumab therapy are eligible;
f) ECOG performance status of 0 or 1;
g) Subjects must have the complete set of baseline (ie, screening) digital radiographic images of lesions and anatomic regions limited to brain, chest, and abdomen within 28 days of first dose of study drug;
h) Provision of baseline DNA samples from peripheral blood for testing of:
* CD86 and CTLA-4 polymorphisms, and
* genome-wide association analysis to identify genetic determinants of immune-related adverse events;
i) Adequate hematologic, renal and hepatic function, specifically:
* WBC * 2500/uL, ANC * 1000/uL,
* Platelets * 75 x 10^3/uL,
* Hemoglobin * 9 g/dL,
* Creatinine * 2.5 x ULN,
* AST/ALT * 3 x ULN for subjects without liver metastasis; * 5 x ULN for subjects with liver metastasis,
* Total bilirubin * 3 x ULN, (except subjects with Gilbert*s Syndrome, who must have a total bilirubin less than 3.0 mg/dL);
j) Accessible for treatment and Follow-up;
3) Age and Reproductive Status
a) Men and women * 18 years of age
b) Women of childbearing potential (WOCBP) and men must be using an acceptable method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the last dose of investigational product] in such a manner that the risk of pregnancy is minimized. See Section 3.3.4 for the definition of WOCBP.
c) 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 investigational product.
d) Women must not be breastfeeding
e) Sexually active fertile men must use effective birth control if their partners are WOCBP.
Exclusion Criteria
1) Target Disease Exceptions
a) Primary ocular melanoma;
b) Active brain metastases with symptoms or requiring corticosteroid treatment;
2) Medical History and Concurrent Diseases
a) Any other malignancy from which the subject has been disease-free for less than 2 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;
b) History of or current active autoimmune diseases, including but not limited to inflammatory bowel diseases, rheumatoid arthritis, autoimmune thyroiditis, autoimmune hepatitis, systemic sclerosis (scleroderma and variants), systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies (eg, Guillain-Barre syndrome). Vitiligo is NOT excluded;
c) Uncontrolled infectious diseases * requires negative tests for clinically suspected HIV, HBV and HCV. If positive results are not indicative of true active or chronic infection, the subject may enter the study after discussion and agreement between the Investigator and the Medical Monitor;
d) History of or current immunodeficiency disease, splenectomy or splenic irradiation;
e) Prior allogeneic stem cell transplantation;
f) 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;
3) Physical and Laboratory Test Findings
a) Not applicable; defined in Inclusion criteria
4) Prohibited Therapies and/or Medications
a) Prior therapy with a B-Raf inhibitor, CTLA-4 or PD-1 antagonists, or PD-L1 or CD137 agonists;
b) Concomitant therapy with any anti-cancer agent, potent immunosuppressive agents, surgery or radiotherapy or other investigational anti-cancer therapies or chronic use of systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses);
c) Prior anti-cancer therapy < 4 weeks prior to randomization;
d) Prior therapies with systemic immunosuppressive agents within prior 2 years (excluding episodic low dose corticosteroids, eg, for treatment of allergic dermatologic conditions); prior therapies with cytotoxic or investigational drugs within 4 weeks of randomization;
e) Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 4 weeks prior to or after any dose of ipilimumab);
f) Treatment with any other investigational products within 4 weeks prior to randomization into this study;
g) Any psychological or medical condition which may interfere with the ability to provide informed consent;
h) Any psychological, familial, cultural/sociological or geographical condition which could potentially hamper compliance with study schedule, procedures and testing;
5) Allergies and Adverse Drug Reaction
a) History of allergic reaction to parenteral administered recombinant protein product;
6) Sex and Reproductive Status
a) Sexually active fertile men not using effective birth control if their partners are WOCBP
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Study Assessments and Primary Endpoint: Safety Assessments: All subjects who<br /><br>receive at least one dose of study treatment (ipilimumab) will be evaluated for<br /><br>safety parameters.<br /><br>Primary Endpoint: All randomized subjects will be evaluated for efficacy<br /><br>analyses. Overall survival (OS) will be defined as the time from the date of<br /><br>randomization until the date of death. For those subjects who have not died, OS<br /><br>will be censored on the last date the subject was known to be alive.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary Objectives:<br /><br>Efficacy:<br /><br>* To compare progression-free survival between doses of 3 mg/kg and 10 mg/kg by<br /><br>mWHO criteria<br /><br>* To compare best overall response rate between doses of 3 mg/kg and 10 mg/kg<br /><br>by mWHO criteria<br /><br>* To compare disease control rate between doses of 3 mg/kg and 10 mg/kg by mWHO<br /><br>criteria<br /><br>* To evaluate duration of response and stable disease for the of 3 mg/kg and 10<br /><br>mg/kg dose groups by mWHO criteria<br /><br>* To evaluate the OS in each of the two dosing groups in the subset of subjects<br /><br>with brain metastases</p><br>