Melanoma
Conditions
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.
Interventions
DRUGIpilimumab
DRUGDacarbazine
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Surviving at 1 Year | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Grade 3-4 Immune-related Adverse Events (irAEs) | 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 | 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. |
Countries
Japan
Participant flow
Pre-assignment details
A total of 21 participants were enrolled, and 15 received treatment.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative reason by sponsor | 1 |
| Overall Study | No longer met study criteria | 5 |
Baseline characteristics
| Characteristic | Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2 |
|---|---|
| Age, Continuous | 55.0 Years STANDARD_DEVIATION 12.66 |
| Age, Customized 65 and older | 5 Participants |
| Age, Customized Younger than 65 | 10 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 | 13 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 | 2 Participants |
| Female Age, Continuous | 47.2 Years STANDARD_DEVIATION 13.26 |
| Female age, customized 50 years and older | 2 Participants |
| Female age, customized Younger than 50 years | 3 Participants |
| Height | 163.0 Centimeters STANDARD_DEVIATION 9.28 |
| M-stage at study entry M0 | 1 Participants |
| M-stage at study entry M1B | 7 Participants |
| M-stage at study entry M1C | 7 Participants |
| Race/Ethnicity, Customized Japanese | 15 Participants |
| Race/Ethnicity, Customized Other | 0 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 15 |
| serious Total, serious adverse events | 14 / 15 |
Outcome results
Primary
Percentage of Participants Surviving at 1 Year
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
Population: All participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2 | Percentage of Participants Surviving at 1 Year | 66.7 Percentage of participants |
Secondary
Number of Participants With Grade 3-4 Immune-related Adverse Events (irAEs)
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
Population: All participants who received at least 1 dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2 | Number of Participants With Grade 3-4 Immune-related Adverse Events (irAEs) | All Grade 3-4 irAEs | 11 Participants |
| Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2 | Number of Participants With Grade 3-4 Immune-related Adverse Events (irAEs) | Skin irAEs | 10 Participants |
| Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2 | Number of Participants With Grade 3-4 Immune-related Adverse Events (irAEs) | Liver irAEs | 12 Participants |
| Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2 | Number of Participants With Grade 3-4 Immune-related Adverse Events (irAEs) | Gastrointestinal irAEs | 6 Participants |
| Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2 | Number of Participants With Grade 3-4 Immune-related Adverse Events (irAEs) | Endocrine irAEs | 3 Participants |
| Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2 | Number of Participants With Grade 3-4 Immune-related Adverse Events (irAEs) | Neurologic irAEs | 0 Participants |
| Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2 | Number of Participants With Grade 3-4 Immune-related Adverse Events (irAEs) | Other irAEs | 2 Participants |
Secondary
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
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.
Population: All participants who received at least 1 dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2 | 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 |
| Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2 | 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 |
| Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2 | 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 |
| Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2 | 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 |
| Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2 | 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 |
| Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2 | 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 |
| Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2 | 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 |
| Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2 | 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 |