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

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ClinicalTrials.gov Identifier: NCT01681212
Recruitment Status : Completed
First Posted : September 7, 2012
Results First Posted : June 11, 2015
Last Update Posted : June 11, 2015
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Melanoma
Interventions Drug: Ipilimumab
Drug: Dacarbazine
Enrollment 21
Recruitment Details  
Pre-assignment Details A total of 21 participants were enrolled, and 15 received treatment.
Arm/Group Title Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2
Hide Arm/Group Description 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, unacceptable toxicity, or withdrawal of 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.
Period Title: Overall Study
Started 21 [1]
Received Treatment 15
Completed 15 [2]
Not Completed 6
Reason Not Completed
No longer met study criteria             5
Administrative reason by sponsor             1
[1]
Enrolled
[2]
Completed=patients who received treatment; not completed=patients who did not receive treatment
Arm/Group Title Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2
Hide Arm/Group Description 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.
Overall Number of Baseline Participants 15
Hide Baseline Analysis Population Description
All participants who received at least 1 dose of treatment medication
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants
55.0  (12.66)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15 participants
Younger than 65 10
65 and older 5
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
Female
5
  33.3%
Male
10
  66.7%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15 participants
Japanese 15
Other 0
Female Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants
47.2  (13.26)
[1]
Measure Description: Data are provided for the 5 women in the study.
M-stage at study entry   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15 participants
M0 1
M1B 7
M1C 7
[1]
Measure Description: M-stage=stage of metastases (M), based on criteria of the American Joint Committee on Cancer. M1A=metastases to skin, subcutaneous tissue, or distant lymph nodes. M1B=metastases to lung. M1C=metastases to all other visceral sites or distant metastases to any site combined with an elevated serum level of lactase dehydrogenase.
Eastern Cooperative Oncology Group (ECOG) Performance Status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15 participants
0 13
1 2
[1]
Measure Description: ECOG scales are used to assess the progress of disease and the disease's effects on daily living abilities and to determine appropriate treatment. Grade 0=fully active; able to carry on all activities without restriction. Grade 1=restricted in strenuous activity but ambulatory; able to perform light work. Grade 2=ambulatory; capable of all self care but unable to work; up more than 50% of waking hours. Grade 3=capable of limited self care, confined to bed or chair more than 50% of waking hours. Grade 4=Completely disabled; cannot carry on any self care; totally confined to bed or chair.
Height  
Mean (Standard Deviation)
Unit of measure:  Centimeters
Number Analyzed 15 participants
163.0  (9.28)
Female age, customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15 participants
Younger than 50 years 3
50 years and older 2
[1]
Measure Description: Data are provided for the 5 women in the study.
1.Primary Outcome
Title Percentage of Participants Surviving at 1 Year
Hide Description 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.
Time Frame At 1 year from start of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug.
Arm/Group Title Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 15
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of participants
66.7
(42.3 to 85.8)
2.Secondary Outcome
Title Number of Participants With Grade 3-4 Immune-related Adverse Events (irAEs)
Hide Description 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.
Time Frame First dose to 90 days following last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug
Arm/Group Title Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 15
Measure Type: Number
Unit of Measure: Participants
All Grade 3-4 irAEs 11
Skin irAEs 10
Liver irAEs 12
Gastrointestinal irAEs 6
Endocrine irAEs 3
Neurologic irAEs 0
Other irAEs 2
3.Secondary Outcome
Title 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
Hide Description 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.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug
Arm/Group Title Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 15
Measure Type: Number
Unit of Measure: Participants
Deaths 5
SAEs 14
Related SAEs 11
AEs leading to discontinuation 9
Related AEs leading to discontinuation 9
AEs Grade 3-4 11
Related AEs 15
Related Grade 3-4 AEs 11
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2
Hide Arm/Group Description 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.
All-Cause Mortality
Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2
Affected / at Risk (%)
Total   14/15 (93.33%) 
Blood and lymphatic system disorders   
Febrile neutropenia  1  1/15 (6.67%) 
Gastrointestinal disorders   
Diarrhoea  1  1/15 (6.67%) 
Colitis  1  1/15 (6.67%) 
Investigations   
Alanine aminotransferase increased  1  10/15 (66.67%) 
Aspartate aminotransferase increased  1  7/15 (46.67%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  1/15 (6.67%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Malignant neoplasm progression  1  3/15 (20.00%) 
Malignant melanoma  1  1/15 (6.67%) 
Nervous system disorders   
Dizziness  1  1/15 (6.67%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2
Affected / at Risk (%)
Total   15/15 (100.00%) 
Blood and lymphatic system disorders   
Anaemia  1  1/15 (6.67%) 
Bone marrow failure  1  1/15 (6.67%) 
Lymph node pain  1  1/15 (6.67%) 
Splenomegaly  1  1/15 (6.67%) 
Neutropenia  1  2/15 (13.33%) 
Leukopenia  1  1/15 (6.67%) 
Endocrine disorders   
Cushingoid  1  1/15 (6.67%) 
Hypophysitis  1  1/15 (6.67%) 
Hypothyroidism  1  2/15 (13.33%) 
Eye disorders   
Vision blurred  1  1/15 (6.67%) 
Gastrointestinal disorders   
Constipation  1  8/15 (53.33%) 
Gastritis  1  1/15 (6.67%) 
Vomiting  1  1/15 (6.67%) 
Diarrhoea  1  5/15 (33.33%) 
Haemorrhoids  1  1/15 (6.67%) 
Nausea  1  7/15 (46.67%) 
Abdominal pain upper  1  1/15 (6.67%) 
Stomatitis  1  1/15 (6.67%) 
Dyspepsia  1  1/15 (6.67%) 
General disorders   
Malaise  1  2/15 (13.33%) 
Influenza like illness  1  2/15 (13.33%) 
Ulcer  1  1/15 (6.67%) 
Mucosal inflammation  1  1/15 (6.67%) 
Oedema peripheral  1  2/15 (13.33%) 
Pyrexia  1  4/15 (26.67%) 
Chest pain  1  1/15 (6.67%) 
Fatigue  1  1/15 (6.67%) 
Injection site pain  1  2/15 (13.33%) 
Oedema  1  1/15 (6.67%) 
Extravasation  1  1/15 (6.67%) 
Hepatobiliary disorders   
Hepatic steatosis  1  1/15 (6.67%) 
Hepatomegaly  1  2/15 (13.33%) 
Infections and infestations   
Oral herpes  1  1/15 (6.67%) 
Sinusitis  1  1/15 (6.67%) 
Fungal infection  1  1/15 (6.67%) 
Nasopharyngitis  1  1/15 (6.67%) 
Herpes zoster  1  1/15 (6.67%) 
Folliculitis  1  1/15 (6.67%) 
Pneumonia  1  1/15 (6.67%) 
Tinea pedis  1  1/15 (6.67%) 
Injury, poisoning and procedural complications   
Fracture  1  1/15 (6.67%) 
Radiation skin injury  1  1/15 (6.67%) 
Investigations   
Blood thyroid stimulating hormone increased  1  2/15 (13.33%) 
Electrocardiogram ST-T change  1  1/15 (6.67%) 
Weight increased  1  1/15 (6.67%) 
Alanine aminotransferase increased  1  7/15 (46.67%) 
Weight decreased  1  4/15 (26.67%) 
Aspartate aminotransferase increased  1  7/15 (46.67%) 
Blood lactate dehydrogenase increased  1  1/15 (6.67%) 
Eosinophil count increased  1  1/15 (6.67%) 
Gamma-glutamyltransferase increased  1  2/15 (13.33%) 
Blood alkaline phosphatase increased  1  1/15 (6.67%) 
Blood bilirubin increased  1  1/15 (6.67%) 
Amylase increased  1  1/15 (6.67%) 
Metabolism and nutrition disorders   
Hyperglycaemia  1  3/15 (20.00%) 
Decreased appetite  1  3/15 (20.00%) 
Diabetes mellitus  1  3/15 (20.00%) 
Hyperkalaemia  1  1/15 (6.67%) 
Musculoskeletal and connective tissue disorders   
Bone pain  1  1/15 (6.67%) 
Spinal osteoarthritis  1  1/15 (6.67%) 
Back pain  1  3/15 (20.00%) 
Muscular weakness  1  1/15 (6.67%) 
Myopathy  1  1/15 (6.67%) 
Pain in extremity  1  1/15 (6.67%) 
Nervous system disorders   
Headache  1  1/15 (6.67%) 
Peripheral sensory neuropathy  1  1/15 (6.67%) 
Presyncope  1  1/15 (6.67%) 
Somnolence  1  2/15 (13.33%) 
Psychiatric disorders   
Insomnia  1  2/15 (13.33%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  2/15 (13.33%) 
Dysphonia  1  2/15 (13.33%) 
Skin and subcutaneous tissue disorders   
Dermatitis contact  1  1/15 (6.67%) 
Swelling face  1  1/15 (6.67%) 
Photosensitivity reaction  1  1/15 (6.67%) 
Pruritus  1  1/15 (6.67%) 
Dermatitis acneiform  1  2/15 (13.33%) 
Drug eruption  1  1/15 (6.67%) 
Alopecia  1  2/15 (13.33%) 
Toxic skin eruption  1  1/15 (6.67%) 
Acne  1  1/15 (6.67%) 
Dry skin  1  2/15 (13.33%) 
Erythema  1  2/15 (13.33%) 
Rash  1  6/15 (40.00%) 
Vascular disorders   
Flushing  1  1/15 (6.67%) 
Vascular pain  1  1/15 (6.67%) 
Phlebitis  1  1/15 (6.67%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
This study was discontinued due to severe liver toxicity.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
EMail: Clinical.Trials@bms.com
Layout table for additonal information
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01681212     History of Changes
Other Study ID Numbers: CA184-202
First Submitted: September 5, 2012
First Posted: September 7, 2012
Results First Submitted: May 22, 2015
Results First Posted: June 11, 2015
Last Update Posted: June 11, 2015