Melanoma
Conditions
Brief summary
The purpose of the study is to determine whether additional doses of ipilimumab have a positive effect on survival in the treatment of advanced melanoma that has progressed after successful initial treatment with ipilimumab.
Interventions
BIOLOGICALIpilimumab
DRUGChemotherapy
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. Key Inclusion Criteria: * Histologic diagnosis of unresectable stage III or IV metastatic melanoma * Prior ipilimumab induction treatment (3 mg/kg) * Documented disease control \[Stable Disease ≥3 months or Partial Response/Complete Response\] after ipilimumab induction * Documented progressive disease following disease control Key
Exclusion criteria
* Patients with brain metastasis are excluded, unless they are free of neurologic symptoms related to metastatic brain lesions and do not receive systemic corticosteroid therapy for the purpose of reducing intracranial inflammation in the 10 days prior to beginning retreatment with ipilimumab * Any intervening anticancer therapy between last dose of ipilimumab induction and ipilimumab retreatment on study * Patients who experienced any grade 3 immune-related adverse event (irAE) (except for endocrinopathies where clinical symptoms were controlled with appropriate hormone replacement therapy) or any grade 4 toxicity during prior treatment with ipilimumab * Patients with a prior irAE that has not improved to grade 1 or better at randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | From randomization to death or last known alive date, assessed up to 15.6 months | Overall survival is defined for each patient as the time between randomization and death. If a patient has not died, he or she will be censored at the time of last contact (last known alive date) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | Every 3 months for approximately 3.5 years after start of randomization and then every 6 months until confirmed and documented progressive disease | DCR is defined per arm as the total number of randomized participants with best overall response as complete response, partial response, or stable disease, divided by the total number of randomized participants in the arm. Bristol-Myers Squibb terminated this study early because the study would not meet its scientific objective in the predefined time frame. Thus, no participants were analyzed. Because the study ended before best overall response could be determined, no participants were analyzed. |
| Best Overall Response Rate (BORR) | Every 3 months for approximately 3.5 years after start of randomization and then every 6 months until confirmed and documented progressive disease | BORR is defined per arm as the total number of randomized patients with a best overall response of complete response or partial response, divided by the total number of randomized patients in the arm. Bristol-Myers Squibb terminated this study early because the study would not meet its scientific objective in the predefined timeframe. Because the study ended before best overall response for all patients was defined, no participant data was analyzed. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Immune-related AEs (irAEs) | From Day 1 of treatment to 90 days after last dose (or to death date for death information) | 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. |
Countries
Austria, France, Germany, Italy, United States
Participant flow
Pre-assignment details
A total of 31 participants were enrolled. Of the 23 who were randomized, 22 received treatment .
Participants by arm
| Arm | Count |
|---|---|
| Ipilimumab, 3 mg/kg Participants received ipilimumab, 3 mg/kg, intravenously by infusion every 3 weeks for a total of 4 doses or until disease progression, unacceptable toxicity, or withdrawal of consent | 18 |
| Chemotherapy Participants received the investigator's choice of chemotherapy, dosed per package instructions. | 5 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative reason by sponsor | 0 | 1 |
| Overall Study | Disease progression | 3 | 3 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Study drug toxicity | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Ipilimumab, 3 mg/kg | Chemotherapy | Total |
|---|---|---|---|
| Age, Continuous | 62.3 Years STANDARD_DEVIATION 11.38 | 64.2 Years STANDARD_DEVIATION 4.32 | 62.7 Years STANDARD_DEVIATION 10.2 |
| Disease Stage at Study Entry Stage III | 1 Participants | 1 Participants | 2 Participants |
| Disease Stage at Study Entry Stage IV | 17 Participants | 4 Participants | 21 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 | 13 Participants | 5 Participants | 18 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 | 5 Participants | 0 Participants | 5 Participants |
| Objective Response to Prior Ipilimumab Treatment Complete response/Partial response | 6 Participants | 0 Participants | 6 Participants |
| Objective Response to Prior Ipilimumab Treatment Stable disease | 12 Participants | 5 Participants | 17 Participants |
| Race/Ethnicity, Customized White | 18 Participants | 5 Participants | 23 Participants |
| Sex: Female, Male Female | 6 Participants | 1 Participants | 7 Participants |
| Sex: Female, Male Male | 12 Participants | 4 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 15 / 18 | 4 / 4 |
| serious Total, serious adverse events | 7 / 18 | 0 / 4 |
Outcome results
Primary
Overall Survival
Overall survival is defined for each patient as the time between randomization and death. If a patient has not died, he or she will be censored at the time of last contact (last known alive date)
Time frame: From randomization to death or last known alive date, assessed up to 15.6 months
Population: All participants who were randomized
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ipilimumab, 3 mg/kg | Overall Survival | 6.3 Months |
| Chemotherapy | Overall Survival | 3.1 Months |
Secondary
Best Overall Response Rate (BORR)
BORR is defined per arm as the total number of randomized patients with a best overall response of complete response or partial response, divided by the total number of randomized patients in the arm. Bristol-Myers Squibb terminated this study early because the study would not meet its scientific objective in the predefined timeframe. Because the study ended before best overall response for all patients was defined, no participant data was analyzed.
Time frame: Every 3 months for approximately 3.5 years after start of randomization and then every 6 months until confirmed and documented progressive disease
Population: All participants who were randomized
Secondary
Disease Control Rate (DCR)
DCR is defined per arm as the total number of randomized participants with best overall response as complete response, partial response, or stable disease, divided by the total number of randomized participants in the arm. Bristol-Myers Squibb terminated this study early because the study would not meet its scientific objective in the predefined time frame. Thus, no participants were analyzed. Because the study ended before best overall response could be determined, no participants were analyzed.
Time frame: Every 3 months for approximately 3.5 years after start of randomization and then every 6 months until confirmed and documented progressive disease
Population: All participants who were randomized
Other Pre-specified
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Immune-related AEs (irAEs)
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.
Time frame: From Day 1 of treatment to 90 days after last dose (or to death date for death information)
Population: All participants who received at least 1 dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ipilimumab, 3 mg/kg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Immune-related AEs (irAEs) | Deaths within 90 days of last dose | 1 Participants |
| Ipilimumab, 3 mg/kg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Immune-related AEs (irAEs) | SAEs | 7 Participants |
| Ipilimumab, 3 mg/kg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Immune-related AEs (irAEs) | AEs leading to discontinuation | 2 Participants |
| Ipilimumab, 3 mg/kg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Immune-related AEs (irAEs) | irAEs | 10 Participants |
| Ipilimumab, 3 mg/kg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Immune-related AEs (irAEs) | Deaths | 5 Participants |
| Chemotherapy | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Immune-related AEs (irAEs) | irAEs | 1 Participants |
| Chemotherapy | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Immune-related AEs (irAEs) | Deaths | 1 Participants |
| Chemotherapy | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Immune-related AEs (irAEs) | Deaths within 90 days of last dose | 0 Participants |
| Chemotherapy | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Immune-related AEs (irAEs) | AEs leading to discontinuation | 0 Participants |
| Chemotherapy | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Immune-related AEs (irAEs) | SAEs | 0 Participants |