Phase 2 Study of Ipilimumab Plus Dacarbazine in Japanese Patients With Advanced Melanoma

Study Overview
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Brief Summary
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The purpose of this study is to determine the survival rate after 1 year of treatment with ipilimumab plus dacarbazine in patients with previously untreated Stage III (unresectable) or Stage IV melanoma.

Official Title
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Phase 2 Study of Ipilimumab Plus Dacarbazine in Japanese Patients With Previously Untreated Unresectable or Metastatic Melanoma

Conditions
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Melanoma

Intervention / Treatment
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* Drug: Ipilimumab
* Drug: Dacarbazine


Participation Criteria
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Eligibility Criteria
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Key inclusion criteria: Japanese patients with histologic diagnosis of malignant melanoma Previously untreated Stage III with N3 (unresectable) or Stage IV melanoma Prior adjuvant melanoma therapy permitted Eastern Cooperative Oncology Group performance status of 0 or 1 Life expectancy of at least 16 weeks in this study Adequate bone marrow and renal and hepatic function, specifically: white blood cell count ≥2500/uL, absolute neutrophil count ≥1000/uL, platelet count ≥75,000/uL, hemoglobin level ≥9.0 g/dL, creatinine level ≤2.5*upper limit of normal (ULN), aspartate transaminase/alanine transaminase level <2.5*ULN for patients without liver metastasis and <5*ULN for patients with liver metastasis, total bilirubin level <1.5*ULN (for those with Gilbert's Syndrome, lower than 3.0 mg/dL) Key exclusion criteria: Evidence of brain metastases on brain imaging Active brain metastases with symptoms or requiring corticosteroid treatment; patients with any other malignancy from which they have been disease-free for fewer 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 Primary ocular or mucosal melanoma History of or current active autoimmune disease History or concurrent disease of gastrointestinal perforations HIV infection; active Hepatitis B or C or human T-lymphotropic virus type1 infection, based on testing performed during the screening period of this study Prior or concomitant therapy with any anticancer agent for melanoma, or other investigational anticancer therapies Prior adjuvant therapy <4 weeks prior to the start of study drug administration Concomitant therapy with immunosuppressive agents, surgery, or radiotherapy Prior treatment with CTLA-4 inhibitors/agonists or other experimental immunotherapy drugs Treatment with other investigational products within 4 weeks prior to initial treatment of study drug

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2<br>During the Induction Period, participants received ipilimumab, 10 mg/kg, as tolerated by intravenous (IV) infusion as 1 single dose during Weeks 1 (Day 1), 4, 7, and 10 for a total of 4 separate doses. During the Maintenance Phase, participants received ipilimumab, 10 mg/kg, as tolerated by IV infusion every 12 weeks, beginning at Week 24, until disease progression or unacceptable toxicity occurred or the patient withdrew consent. Participants also received dacarbazine, 850 mg/m^2, by IV infusion over 30 to 60 minutes, starting on Week 1 and repeated every 3 weeks until Week 22. Dacarbazine was dosed on the same day as ipilimumab, when applicable, after the ipilimumab dose. | Drug: Ipilimumab<br> <br> * Other names: BMS-734016;Drug: Dacarbazine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Surviving at 1 Year | Survival rate=percentage of participants surviving at 1 year following start of study drug. Every effort was made to collect survival data on all patients, including those withdrawn from treatment for any reason. If the death of a patient was not reported, the patient's last known alive date was recorded. Confidence intervals were computed using the Clopper-Pearson method. | At 1 year from start of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Grade 3-4 Immune-related Adverse Events (irAEs) | irAEs are adverse events of unknown cause, consistent with an immune phenomenon, and considered to be causally related to drug exposure. Six subcategories of irAE are assessed: gastrointestinal, liver, skin, endocrine, neurologic, and other. The irAEs are programmatically determined from a predefined list of MedDRA terms. irAEs will be measured every 3 weeks in induction phase, every 6 weeks in Maintenance Phase to Week 48, and every 12 weeks until Progressive Disease. Grading criteria: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death. | First dose to 90 days following last dose of study drug | 
| Number of Patients Who Died and Who Had Serious Adverse Events (SAEs), Treatment-related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, Grade 3-4 AEs, and Related Grade 3-4 AEs | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=having certain, probable, possible, or unknown relationship to study drug. Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening or disabling; Grade 5=death. | First dose to 90 days following last dose of study drug. All deaths were poststudy, occurring more than 90 days after the last dose of study drug. |