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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01681212
Recruitment Status : Completed
First Posted : September 7, 2012
Results First Posted : June 11, 2015
Last Update Posted : June 11, 2015
Information provided by (Responsible Party):
Bristol-Myers Squibb

Tracking Information
First Submitted Date  ICMJE September 5, 2012
First Posted Date  ICMJE September 7, 2012
Results First Submitted Date  ICMJE May 22, 2015
Results First Posted Date  ICMJE June 11, 2015
Last Update Posted Date June 11, 2015
Study Start Date  ICMJE October 2012
Actual Primary Completion Date May 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 9, 2015)
Percentage of Participants Surviving at 1 Year [ Time Frame: At 1 year from start of study drug ]
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 Every effort was made to collect survival data on all patients, including those withdrawn from treatment for any reason.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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 5, 2012)
Survival rate defined as the proportion of subjects who are alive after at least one year of follow up following the first dose of study therapy [ Time Frame: At 1 year after start of study drugs treatment ]
Change History Complete list of historical versions of study NCT01681212 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 9, 2015)
  • 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 ]
    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. ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 5, 2012)
Frequency of Grade 3-4 Immune-related Adverse Events (irAEs) [ Time Frame: Up to 90 days following the last dose of Ipilimumab ]
irAEs will be measured every 3 weeks in induction phase, every 6 weeks in maintenance to Week 48, and every 12 weeks to Progressive Disease (PD)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Phase 2 Study of Ipilimumab Plus Dacarbazine in Japanese Patients With Advanced Melanoma
Official Title  ICMJE Phase 2 Study of Ipilimumab Plus Dacarbazine in Japanese Patients With Previously Untreated Unresectable or Metastatic Melanoma
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Melanoma
Intervention  ICMJE
  • Drug: Ipilimumab
    Other Name: BMS-734016
  • Drug: Dacarbazine
Study Arms  ICMJE 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
  • Drug: Dacarbazine
Publications * Yamazaki N, Uhara H, Fukushima S, Uchi H, Shibagaki N, Kiyohara Y, Tsutsumida A, Namikawa K, Okuyama R, Otsuka Y, Tokudome T. Phase II study of the immune-checkpoint inhibitor ipilimumab plus dacarbazine in Japanese patients with previously untreated, unresectable or metastatic melanoma. Cancer Chemother Pharmacol. 2015 Nov;76(5):969-75. doi: 10.1007/s00280-015-2870-0. Epub 2015 Sep 25.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 9, 2015)
Original Estimated Enrollment  ICMJE
 (submitted: September 5, 2012)
Actual Study Completion Date  ICMJE May 2014
Actual Primary Completion Date May 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01681212
Other Study ID Numbers  ICMJE CA184-202
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bristol-Myers Squibb
Study Sponsor  ICMJE Bristol-Myers Squibb
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account Bristol-Myers Squibb
Verification Date June 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP