Trial Outcomes & Findings for Phase 2 Study of Ipilimumab Plus Dacarbazine in Japanese Patients With Advanced Melanoma (NCT NCT01681212)
NCT ID: NCT01681212
Last Updated: 2015-06-11
Results Overview
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 Every effort was made to collect survival data on all patients, including those withdrawn from treatment for any reason.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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
21 participants
Primary outcome timeframe
At 1 year from start of study drug
Results posted on
2015-06-11
Participant Flow
A total of 21 participants were enrolled, and 15 received treatment.
Participant milestones
| Measure |
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, 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.
|
|---|---|
|
Overall Study
STARTED
|
21
|
|
Overall Study
Received Treatment
|
15
|
|
Overall Study
COMPLETED
|
15
|
|
Overall Study
NOT COMPLETED
|
6
|
Reasons for withdrawal
| Measure |
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, 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.
|
|---|---|
|
Overall Study
No longer met study criteria
|
5
|
|
Overall Study
Administrative reason by sponsor
|
1
|
Baseline Characteristics
Phase 2 Study of Ipilimumab Plus Dacarbazine in Japanese Patients With Advanced Melanoma
Baseline characteristics by cohort
| Measure |
Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2
n=15 Participants
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.
|
|---|---|
|
Age, Continuous
|
55.0 Years
STANDARD_DEVIATION 12.66 • n=5 Participants
|
|
Age, Customized
Younger than 65
|
10 Participants
n=5 Participants
|
|
Age, Customized
65 and older
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Japanese
|
15 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=5 Participants
|
|
Female Age, Continuous
|
47.2 Years
STANDARD_DEVIATION 13.26 • n=5 Participants
|
|
M-stage at study entry
M0
|
1 Participants
n=5 Participants
|
|
M-stage at study entry
M1B
|
7 Participants
n=5 Participants
|
|
M-stage at study entry
M1C
|
7 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
0
|
13 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
1
|
2 Participants
n=5 Participants
|
|
Height
|
163.0 Centimeters
STANDARD_DEVIATION 9.28 • n=5 Participants
|
|
Female age, customized
Younger than 50 years
|
3 Participants
n=5 Participants
|
|
Female age, customized
50 years and older
|
2 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: At 1 year from start of study drugPopulation: All participants who received at least 1 dose 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.
Outcome measures
| Measure |
Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2
n=15 Participants
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.
|
|---|---|
|
Percentage of Participants Surviving at 1 Year
|
66.7 Percentage of participants
Interval 42.3 to 85.8
|
SECONDARY outcome
Timeframe: First dose to 90 days following last dose of study drugPopulation: All participants who received at least 1 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.
Outcome measures
| Measure |
Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2
n=15 Participants
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.
|
|---|---|
|
Number of Participants With Grade 3-4 Immune-related Adverse Events (irAEs)
All Grade 3-4 irAEs
|
11 Participants
|
|
Number of Participants With Grade 3-4 Immune-related Adverse Events (irAEs)
Skin irAEs
|
10 Participants
|
|
Number of Participants With Grade 3-4 Immune-related Adverse Events (irAEs)
Liver irAEs
|
12 Participants
|
|
Number of Participants With Grade 3-4 Immune-related Adverse Events (irAEs)
Gastrointestinal irAEs
|
6 Participants
|
|
Number of Participants With Grade 3-4 Immune-related Adverse Events (irAEs)
Endocrine irAEs
|
3 Participants
|
|
Number of Participants With Grade 3-4 Immune-related Adverse Events (irAEs)
Neurologic irAEs
|
0 Participants
|
|
Number of Participants With Grade 3-4 Immune-related Adverse Events (irAEs)
Other irAEs
|
2 Participants
|
SECONDARY outcome
Timeframe: 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.Population: All participants who received at least 1 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.
Outcome measures
| Measure |
Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2
n=15 Participants
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.
|
|---|---|
|
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
Deaths
|
5 Participants
|
|
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
SAEs
|
14 Participants
|
|
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
Related SAEs
|
11 Participants
|
|
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
AEs leading to discontinuation
|
9 Participants
|
|
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
Related AEs leading to discontinuation
|
9 Participants
|
|
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
AEs Grade 3-4
|
11 Participants
|
|
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
Related AEs
|
15 Participants
|
|
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
Related Grade 3-4 AEs
|
11 Participants
|
Adverse Events
Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2
Serious events: 14 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2
n=15 participants at risk
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.
|
|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression
|
20.0%
3/15
|
|
Investigations
Alanine aminotransferase increased
|
66.7%
10/15
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.7%
1/15
|
|
Gastrointestinal disorders
Diarrhoea
|
6.7%
1/15
|
|
Investigations
Aspartate aminotransferase increased
|
46.7%
7/15
|
|
Nervous system disorders
Dizziness
|
6.7%
1/15
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
6.7%
1/15
|
|
Gastrointestinal disorders
Colitis
|
6.7%
1/15
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma
|
6.7%
1/15
|
Other adverse events
| Measure |
Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2
n=15 participants at risk
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.
|
|---|---|
|
Gastrointestinal disorders
Dyspepsia
|
6.7%
1/15
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
13.3%
2/15
|
|
General disorders
Extravasation
|
6.7%
1/15
|
|
Infections and infestations
Folliculitis
|
6.7%
1/15
|
|
Hepatobiliary disorders
Hepatomegaly
|
13.3%
2/15
|
|
Endocrine disorders
Hypothyroidism
|
13.3%
2/15
|
|
Infections and infestations
Pneumonia
|
6.7%
1/15
|
|
Nervous system disorders
Presyncope
|
6.7%
1/15
|
|
Nervous system disorders
Somnolence
|
13.3%
2/15
|
|
Infections and infestations
Tinea pedis
|
6.7%
1/15
|
|
Investigations
Blood thyroid stimulating hormone increased
|
13.3%
2/15
|
|
Gastrointestinal disorders
Constipation
|
53.3%
8/15
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
13.3%
2/15
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
6.7%
1/15
|
|
Investigations
Electrocardiogram ST-T change
|
6.7%
1/15
|
|
Nervous system disorders
Headache
|
6.7%
1/15
|
|
General disorders
Malaise
|
13.3%
2/15
|
|
Infections and infestations
Oral herpes
|
6.7%
1/15
|
|
Blood and lymphatic system disorders
Anaemia
|
6.7%
1/15
|
|
Blood and lymphatic system disorders
Bone marrow failure
|
6.7%
1/15
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
6.7%
1/15
|
|
Vascular disorders
Flushing
|
6.7%
1/15
|
|
Injury, poisoning and procedural complications
Fracture
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
20.0%
3/15
|
|
General disorders
Influenza like illness
|
13.3%
2/15
|
|
Blood and lymphatic system disorders
Lymph node pain
|
6.7%
1/15
|
|
Musculoskeletal and connective tissue disorders
Spinal osteoarthritis
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
Swelling face
|
6.7%
1/15
|
|
General disorders
Ulcer
|
6.7%
1/15
|
|
Investigations
Weight increased
|
6.7%
1/15
|
|
Investigations
Alanine aminotransferase increased
|
46.7%
7/15
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
20.0%
3/15
|
|
Gastrointestinal disorders
Gastritis
|
6.7%
1/15
|
|
General disorders
Mucosal inflammation
|
6.7%
1/15
|
|
General disorders
Oedema peripheral
|
13.3%
2/15
|
|
Skin and subcutaneous tissue disorders
Photosensitivity reaction
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
6.7%
1/15
|
|
Injury, poisoning and procedural complications
Radiation skin injury
|
6.7%
1/15
|
|
Infections and infestations
Sinusitis
|
6.7%
1/15
|
|
Vascular disorders
Vascular pain
|
6.7%
1/15
|
|
Gastrointestinal disorders
Vomiting
|
6.7%
1/15
|
|
Endocrine disorders
Cushingoid
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
Decreased appetite
|
20.0%
3/15
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
13.3%
2/15
|
|
Gastrointestinal disorders
Diarrhoea
|
33.3%
5/15
|
|
Skin and subcutaneous tissue disorders
Drug eruption
|
6.7%
1/15
|
|
Infections and infestations
Fungal infection
|
6.7%
1/15
|
|
Gastrointestinal disorders
Haemorrhoids
|
6.7%
1/15
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
6.7%
1/15
|
|
Infections and infestations
Nasopharyngitis
|
6.7%
1/15
|
|
Gastrointestinal disorders
Nausea
|
46.7%
7/15
|
|
Blood and lymphatic system disorders
Splenomegaly
|
6.7%
1/15
|
|
Investigations
Weight decreased
|
26.7%
4/15
|
|
Gastrointestinal disorders
Abdominal pain upper
|
6.7%
1/15
|
|
Investigations
Aspartate aminotransferase increased
|
46.7%
7/15
|
|
Investigations
Blood lactate dehydrogenase increased
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
20.0%
3/15
|
|
Psychiatric disorders
Insomnia
|
13.3%
2/15
|
|
Blood and lymphatic system disorders
Neutropenia
|
13.3%
2/15
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
6.7%
1/15
|
|
General disorders
Pyrexia
|
26.7%
4/15
|
|
Eye disorders
Vision blurred
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
13.3%
2/15
|
|
General disorders
Chest pain
|
6.7%
1/15
|
|
Investigations
Eosinophil count increased
|
6.7%
1/15
|
|
General disorders
Fatigue
|
6.7%
1/15
|
|
Investigations
Gamma-glutamyltransferase increased
|
13.3%
2/15
|
|
Hepatobiliary disorders
Hepatic steatosis
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
6.7%
1/15
|
|
Endocrine disorders
Hypophysitis
|
6.7%
1/15
|
|
General disorders
Injection site pain
|
13.3%
2/15
|
|
Blood and lymphatic system disorders
Leukopenia
|
6.7%
1/15
|
|
Musculoskeletal and connective tissue disorders
Myopathy
|
6.7%
1/15
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
6.7%
1/15
|
|
Vascular disorders
Phlebitis
|
6.7%
1/15
|
|
Gastrointestinal disorders
Stomatitis
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
Toxic skin eruption
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
Acne
|
6.7%
1/15
|
|
Investigations
Blood alkaline phosphatase increased
|
6.7%
1/15
|
|
Investigations
Blood bilirubin increased
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
13.3%
2/15
|
|
Skin and subcutaneous tissue disorders
Erythema
|
13.3%
2/15
|
|
Infections and infestations
Herpes zoster
|
6.7%
1/15
|
|
General disorders
Oedema
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
Rash
|
40.0%
6/15
|
|
Investigations
Amylase increased
|
6.7%
1/15
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER