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

This study has been completed.
Information provided by (Responsible Party):
Bristol-Myers Squibb Identifier:
First received: September 5, 2012
Last updated: June 9, 2015
Last verified: June 2015
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.

Condition Intervention Phase
Drug: Ipilimumab
Drug: Dacarbazine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2 Study of Ipilimumab Plus Dacarbazine in Japanese Patients With Previously Untreated Unresectable or Metastatic Melanoma

Resource links provided by NLM:

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Percentage of Participants Surviving at 1 Year [ Time Frame: At 1 year from start of study drug ] [ Designated as safety issue: No ]
    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 Every effort was made to collect survival data on all patients, including those withdrawn from treatment for any reason.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.

Secondary Outcome Measures:
  • Number of Participants With Grade 3-4 Immune-related Adverse Events (irAEs) [ Time Frame: First dose to 90 days following last dose of study drug ] [ Designated as safety issue: Yes ]
    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.

  • 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 [ Time Frame: 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. ] [ Designated as safety issue: Yes ]
    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.

Enrollment: 21
Study Start Date: October 2012
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2
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
Other Name: BMS-734016
Drug: Dacarbazine


Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
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Please refer to this study by its identifier: NCT01681212

Local Institution
Fukuoka-shi, Fukuoka, Japan, 8128582
Local Institution
Kumamoto-shi, Kumamoto, Japan, 8608556
Local Institution
Matsumoto-shi, Nagano, Japan, 3908621
Local Institution
Sunto-gun, Shizuoka, Japan, 4118777
Local Institution
Chuo-ku, Tokyo, Japan, 1040045
Local Institution
Chuo-shi, Yamanashi, Japan, 4093898
Sponsors and Collaborators
Bristol-Myers Squibb
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb Identifier: NCT01681212     History of Changes
Other Study ID Numbers: CA184-202
Study First Received: September 5, 2012
Results First Received: May 22, 2015
Last Updated: June 9, 2015
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas processed this record on November 24, 2015