Small Cell Lung Carcinoma
Conditions
Brief summary
The purpose of the study is to determine whether the addition of Ipilimumab to Etoposide and Platinum therapy will extend the lives of patients with Extensive-Stage Disease Small Cell Lung Cancer (ED-SCLC) more than Etoposide and Platinum therapy alone.
Interventions
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
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: * Extensive-Stage Disease Small Cell Lung Cancer (ED-SCLC) * Eastern Cooperative Oncology Group (ECOG) of 0 or 1
Exclusion criteria
* Prior systemic therapy for lung cancer * Symptomatic Central Nervous System (CNS) metastases * History of autoimmune disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) in Participants Who Received at Least One Dose of Blinded Study Therapy | Randomization until date of death, up to March 2015, approximately 38 months | Overall Survival was defined as the time from the date of randomization until the date of death from any cause. For participants without documentation of death, OS was censored on the last date the participant was known to be alive. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival in All Randomized Participants | From randomization until date of death, up to March 2015, approximately 38 months | Overall Survival was defined as the time from the date of randomization until the date of death from any cause. For participants without documentation of death, OS was censored on the last date the participant was known to be alive. |
| Progression Free Survival (PFS) Time in Participants Who Have Received at Least One Dose of Blinded Study Therapy | From randomization until disease progression, up to March 2015, approximately 38 months | Progression-Free Survival was defined as the time from the date of randomization to the date of progression per modified World Health Organization (mWHO) criteria or death, whichever occured first. A participant who died without reported progression per mWHO criteria was considered progressed on the date of death. For those participants who remained alive and did not progress, PFS was censored on the date of last evaluable tumor assessment. For those participants who remained alive and had no recorded post-baseline tumor assessment, PFS was censored on the day of randomization. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Czechia, France, Germany, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Mexico, Netherlands, Peru, Poland, Portugal, Romania, Russia, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Thailand, United Kingdom, United States
Participant flow
Pre-assignment details
Of the 1414 enrolled participants, 566 participants each were randomized to Ipilimumab and placebo arms. The remaining 282 participants were not randomized, the most frequently reported reason being that the participants no longer met study criteria.
Participants by arm
| Arm | Count |
|---|---|
| Ipilimumab and Platinum/Etoposide Participants received platinum/etoposide (investigator's choice of platinum) every 3 weeks for 4 cycles with ipilimumab (10 mg/kg IV) every 3 weeks from cycle 3-6 of Induction phase. During the maintenance phase, ipilimumab (10 mg/kg IV) was administered every 12 weeks, beginning 9-12 weeks after the last induction dose, for a maximum treatment period of 3 years from the first dose of ipilimumab. | 478 |
| Placebo and Platinum/Etoposide Participants received platinum/etoposide (investigator's choice of platinum) every 3 weeks for 4 cycles with placebo every 3 weeks from cycle 3-6 during the Induction phase. During the maintenance phase, placebo was administered every 12 weeks, beginning 9-12 weeks after the last Induction dose, for a maximum treatment period of 3 years from the first dose of placebo. | 476 |
| Total | 954 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Lead-in Chemotherapy | Adverse event unrelated to study drug | 21 | 19 |
| Lead-in Chemotherapy | Death | 3 | 3 |
| Lead-in Chemotherapy | Disease progression | 33 | 32 |
| Lead-in Chemotherapy | Lost to Follow-up | 2 | 0 |
| Lead-in Chemotherapy | No longer meets study criteria | 3 | 7 |
| Lead-in Chemotherapy | Other | 2 | 2 |
| Lead-in Chemotherapy | Study drug toxicity | 6 | 10 |
| Lead-in Chemotherapy | Withdrawal by Subject | 14 | 12 |
| Randomization | Adverse Event unrelated to study drug | 1 | 0 |
| Randomization | Disease progression | 0 | 2 |
| Randomization | Other | 0 | 1 |
| Randomization | Subject no longer meets study criteria | 1 | 2 |
| Randomization | Withdrawal by Subject | 2 | 0 |
| Treatment With Blinded Study Therapy | Administrative reason by sponsor | 2 | 3 |
| Treatment With Blinded Study Therapy | Adverse event unrelated to study drug | 27 | 19 |
| Treatment With Blinded Study Therapy | Death | 5 | 6 |
| Treatment With Blinded Study Therapy | Disease progression | 318 | 415 |
| Treatment With Blinded Study Therapy | Lost to Follow-up | 2 | 1 |
| Treatment With Blinded Study Therapy | Maximum clinical benefit | 1 | 2 |
| Treatment With Blinded Study Therapy | No longer meets study criteria | 1 | 2 |
| Treatment With Blinded Study Therapy | Not reported | 2 | 2 |
| Treatment With Blinded Study Therapy | Other/Unspecified | 5 | 4 |
| Treatment With Blinded Study Therapy | Poor/non-compliance | 1 | 0 |
| Treatment With Blinded Study Therapy | Study drug toxicity | 87 | 9 |
| Treatment With Blinded Study Therapy | Subject request to discontinue treatment | 15 | 8 |
| Treatment With Blinded Study Therapy | Withdrawal by Subject | 12 | 5 |
Baseline characteristics
| Characteristic | Ipilimumab and Platinum/Etoposide | Placebo and Platinum/Etoposide | Total |
|---|---|---|---|
| Age, Continuous | 61.3 years STANDARD_DEVIATION 8.9 | 62.6 years STANDARD_DEVIATION 8.61 | 61.9 years STANDARD_DEVIATION 8.78 |
| Sex: Female, Male Female | 161 Participants | 150 Participants | 311 Participants |
| Sex: Female, Male Male | 317 Participants | 326 Participants | 643 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 519 / 562 | 520 / 561 |
| serious Total, serious adverse events | 316 / 562 | 278 / 561 |
Outcome results
Primary
Overall Survival (OS) in Participants Who Received at Least One Dose of Blinded Study Therapy
Overall Survival was defined as the time from the date of randomization until the date of death from any cause. For participants without documentation of death, OS was censored on the last date the participant was known to be alive.
Time frame: Randomization until date of death, up to March 2015, approximately 38 months
Population: All randomized participants who received at least one dose of blinded study therapy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ipilimumab and Platinum/Etoposide | Overall Survival (OS) in Participants Who Received at Least One Dose of Blinded Study Therapy | 10.97 months |
| Placebo and Platinum/Etoposide | Overall Survival (OS) in Participants Who Received at Least One Dose of Blinded Study Therapy | 10.94 months |
p-value: 0.377595% CI: [0.807, 1.085]Log Rank
Secondary
Overall Survival in All Randomized Participants
Overall Survival was defined as the time from the date of randomization until the date of death from any cause. For participants without documentation of death, OS was censored on the last date the participant was known to be alive.
Time frame: From randomization until date of death, up to March 2015, approximately 38 months
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ipilimumab and Platinum/Etoposide | Overall Survival in All Randomized Participants | 10.22 months |
| Placebo and Platinum/Etoposide | Overall Survival in All Randomized Participants | 9.95 months |
p-value: 0.567895% CI: [0.838, 1.102]Log Rank
Secondary
Progression Free Survival (PFS) Time in Participants Who Have Received at Least One Dose of Blinded Study Therapy
Progression-Free Survival was defined as the time from the date of randomization to the date of progression per modified World Health Organization (mWHO) criteria or death, whichever occured first. A participant who died without reported progression per mWHO criteria was considered progressed on the date of death. For those participants who remained alive and did not progress, PFS was censored on the date of last evaluable tumor assessment. For those participants who remained alive and had no recorded post-baseline tumor assessment, PFS was censored on the day of randomization.
Time frame: From randomization until disease progression, up to March 2015, approximately 38 months
Population: All randomized participants who received at least one dose of blinded study therapy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ipilimumab and Platinum/Etoposide | Progression Free Survival (PFS) Time in Participants Who Have Received at Least One Dose of Blinded Study Therapy | 4.63 months |
| Placebo and Platinum/Etoposide | Progression Free Survival (PFS) Time in Participants Who Have Received at Least One Dose of Blinded Study Therapy | 4.44 months |
p-value: 0.016195% CI: [0.747, 0.971]Log Rank