Melanoma
Conditions
Brief summary
The purpose of this study is to determine whether Ipilimumab will extend the life of chinese patients with Chemotherapy Naive Stage IV Melanoma more than Dacarbazine as well as to examine safety in this patient population.
Interventions
DRUGIpilimumab
DRUGDacarbazine
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Chinese males and females ≥ 18 years of age * Histologic diagnosis of malignant melanoma * Chemotherapy naive Stage IV melanoma (AJCC 2010) * Life expectancy of ≥ 16 weeks * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Exclusion criteria
* Evidence of brain metastases on brain imaging * Primary ocular or mucosal melanoma * Any other malignancy from which the patient has been disease-free for less than 5 years * BRAF status cannot be determined by Screening test * Human Immunodeficiency Virus (HIV) positive or hepatitis B surface antigen (HBsAg) positive, or active Hepatitis C infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Two-Years Survival Rate | 24 months | Two-year survival rate is defined as the probability that a subject is alive at 2 years following the randomization date and will be estimated via the Kaplan-Meier (KM) method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Approximately 43 months | OS is defined for each subject as the time between randomization date and the date of death (of any cause). |
| Progression Free Survival ( PFS) | Approximately 43 months | PFS is defined for each subject as the time between randomization date and the date of progression or death, whichever occurs first. |
| Disease Control Rate ( DCR ) | Approximately 43 months | Primary DCR is defined as the number of subjects in the arm with Best Overall Response (BOR) of complete response (CR), partial response (PR), or stable disease (SD), divided by the total number of randomized subjects in the arm. |
| One-Year Survival Rate | Approximately 43 months | Survival rate at 1 year is defined as the probability that a subject is alive at 1 year following the randomization date and will be estimated via the Kaplan-Meier (KM) method. |
| Duration of Response ( DoR) | Approximately 43 months | DoR definition for the response evaluable subjects whose BOR is CR or PR is defined as the time between the date of response of CR or PR (whichever occurs first) and the first date of progressive disease (PD) or the date of death (whichever occurs first). |
| Duration of Stable Disease ( DoSD ) | Approximately 43 months | Primary duration of stable disease (DoSD) definition for the randomized subjects whose BOR is SD is defined as the time between the randomization date and the first date of PD or the date of death (whichever occurs first). |
| Best Overall Response Rate ( BORR ) | Approximately 43 months | BORR definition is defined as the number of subjects in the arm with a BOR of CR or PR, divided by the total number of randomized subjects in the arm. |
Countries
China
Participant flow
Pre-assignment details
182 participants were enrolled, 68 were not randomized, reasons for not being randomized:3 participants withdrew consent and 65 no longer meet study criteria.
Participants by arm
| Arm | Count |
|---|---|
| Ipilimumab (3 mg/kg) Ipilimumab 3 mg/kg to be administered via intravenous infusion over 90 minutes at Weeks 1, 4, 7 and 10, for a total of four doses in Induction (and Re-Induction for those randomized to the ipilimumab arm who qualify) | 122 |
| Dacarbazine (250 mg/m2) DTIC 250 mg/m2 - Day 1 - 5, to be administered via intravenous infusion at Weeks 1, 4, 7, 10, 13, 16,19, and 22. | 60 |
| Total | 182 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Randomization | Lost to Follow-up | 0 | 1 |
| Randomization | Withdrawal by Subject | 0 | 6 |
| Treatment | Adverse event not related to study drug | 1 | 0 |
| Treatment | Completed treatment | 40 | 12 |
| Treatment | Death | 1 | 0 |
| Treatment | Disease progression | 71 | 32 |
| Treatment | Participant dicontinued study treatment | 7 | 9 |
| Treatment | Participant drug toxicity | 1 | 0 |
| Treatment | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Dacarbazine (250 mg/m2) | Total | Ipilimumab (3 mg/kg) |
|---|---|---|---|
| Age, Continuous | 54.3 years STANDARD_DEVIATION 13.39 | 53.8 years STANDARD_DEVIATION 13.56 | 53.6 years STANDARD_DEVIATION 13.69 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 60 Participants | 182 Participants | 122 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 60 Participants | 182 Participants | 122 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 26 Participants | 79 Participants | 53 Participants |
| Sex: Female, Male Male | 34 Participants | 103 Participants | 69 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 93 / 122 | 39 / 53 |
| other Total, other adverse events | 118 / 122 | 48 / 53 |
| serious Total, serious adverse events | 34 / 122 | 12 / 53 |
Outcome results
Primary
Two-Years Survival Rate
Two-year survival rate is defined as the probability that a subject is alive at 2 years following the randomization date and will be estimated via the Kaplan-Meier (KM) method.
Time frame: 24 months
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ipilimumab (3 mg/kg) | Two-Years Survival Rate | 33.98 Percentage of Participants |
| Dacarbazine (250 mg/m2) | Two-Years Survival Rate | 34.09 Percentage of Participants |
p-value: 0.5059Chi-squared
Secondary
Best Overall Response Rate ( BORR )
BORR definition is defined as the number of subjects in the arm with a BOR of CR or PR, divided by the total number of randomized subjects in the arm.
Time frame: Approximately 43 months
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ipilimumab (3 mg/kg) | Best Overall Response Rate ( BORR ) | 8.2 Percentage of participants |
| Dacarbazine (250 mg/m2) | Best Overall Response Rate ( BORR ) | 8.3 Percentage of participants |
p-value: 0.973880% CI: [0.48, 2.03]Cochran-Mantel-Haenszel
Secondary
Disease Control Rate ( DCR )
Primary DCR is defined as the number of subjects in the arm with Best Overall Response (BOR) of complete response (CR), partial response (PR), or stable disease (SD), divided by the total number of randomized subjects in the arm.
Time frame: Approximately 43 months
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ipilimumab (3 mg/kg) | Disease Control Rate ( DCR ) | 32 Percentage of participants |
| Dacarbazine (250 mg/m2) | Disease Control Rate ( DCR ) | 31.7 Percentage of participants |
p-value: 0.993280% CI: [0.64, 1.55]Cochran-Mantel-Haenszel
Secondary
Duration of Response ( DoR)
DoR definition for the response evaluable subjects whose BOR is CR or PR is defined as the time between the date of response of CR or PR (whichever occurs first) and the first date of progressive disease (PD) or the date of death (whichever occurs first).
Time frame: Approximately 43 months
Population: All randomized participants with response
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ipilimumab (3 mg/kg) | Duration of Response ( DoR) | 8.99 Months |
| Dacarbazine (250 mg/m2) | Duration of Response ( DoR) | 7.98 Months |
Secondary
Duration of Stable Disease ( DoSD )
Primary duration of stable disease (DoSD) definition for the randomized subjects whose BOR is SD is defined as the time between the randomization date and the first date of PD or the date of death (whichever occurs first).
Time frame: Approximately 43 months
Population: All randomized participants with BOR as stable disease
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ipilimumab (3 mg/kg) | Duration of Stable Disease ( DoSD ) | 6.83 Months |
| Dacarbazine (250 mg/m2) | Duration of Stable Disease ( DoSD ) | 9.40 Months |
Secondary
One-Year Survival Rate
Survival rate at 1 year is defined as the probability that a subject is alive at 1 year following the randomization date and will be estimated via the Kaplan-Meier (KM) method.
Time frame: Approximately 43 months
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ipilimumab (3 mg/kg) | One-Year Survival Rate | 61.68 Percentage of Participants |
| Dacarbazine (250 mg/m2) | One-Year Survival Rate | 64.11 Percentage of Participants |
p-value: 0.6202Chi-squared
Secondary
Overall Survival (OS)
OS is defined for each subject as the time between randomization date and the date of death (of any cause).
Time frame: Approximately 43 months
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ipilimumab (3 mg/kg) | Overall Survival (OS) | 15.08 Months |
| Dacarbazine (250 mg/m2) | Overall Survival (OS) | 14.55 Months |
p-value: 0.726780% CI: [0.87, 1.45]Log Rank
Secondary
Progression Free Survival ( PFS)
PFS is defined for each subject as the time between randomization date and the date of progression or death, whichever occurs first.
Time frame: Approximately 43 months
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ipilimumab (3 mg/kg) | Progression Free Survival ( PFS) | 2.60 Months |
| Dacarbazine (250 mg/m2) | Progression Free Survival ( PFS) | 1.84 Months |
p-value: 0.250380% CI: [0.71, 1.15]Log Rank