Lung Cancer - Non Small Cell Squamous
Conditions
Brief summary
The purpose of the study is to determine whether Ipilimumab plus Paclitaxel and Carboplatin will extend the lives of patients with squamous only non small cell lung cancer more than placebo plus Paclitaxel and Carboplatin.
Detailed description
The primary objective is to compare Overall Survival (OS) of participants with Stage IV/recurrent NSCLC of squamous histology who have been randomized to ipilimumab in addition to paclitaxel and carboplatin versus placebo in addition to paclitaxel and carboplatin, and have received at least one dose of blinded study therapy (ipilimumab or placebo).
Interventions
DRUGIpilimumab
DRUGPlacebo
DRUGPaclitaxel
DRUGCarboplatin
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: * Non small cell lung cancer (NSCLC) - squamous cell * Stage IV or recurrent NSCLC * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Exclusion criteria
* Brain Metastases * Autoimmune diseases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) in Participants Who Received at Least One Dose of Blinded Study Therapy at Primary Endpoint | Randomization until 518 deaths were observed in randomized participants treated with at least one dose of blinded study therapy and 705 deaths were observed in all randomized participants, up to June 2015 (approximately 48 months post study start) | Overall Survival (OS) was defined as the time from randomization to the date of death. Participants that had not died were censored at last known date alive. Median OS time was calculated using Kaplan-Meier Estimates. Analysis for the Primary Endpoint occurred when the following 2 conditions were both met: (1) 518 deaths were observed in randomized participants treated with at least one dose of blinded study therapy and (2) 705 deaths were observed in all randomized participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) in All Randomized Participants at Primary Endpoint | Randomization until 518 deaths were observed in randomized participants treated with at least one dose of blinded study therapy and 705 deaths were observed in all randomized participants, up to June 2015 (approximately 48 months post study start) | Overall Survival (OS) was defined as the time from randomization to the date of death. Participants that had not died were censored at last known date alive. Median OS time was calculated using Kaplan-Meier Estimates. Analysis for the Primary Endpoint occurred when the following 2 conditions were both met: (1) 518 deaths were observed in randomized participants treated with at least one dose of blinded study therapy and (2) 705 deaths were observed in all randomized participants. |
| Median Number of Months With Progression Free Survival (PFS) Per mWHO in Participants Who Have Received at Least One Dose of Blinded Study Therapy at Primary Endpoint | Randomization until 518 deaths were observed in randomized participants treated with at least one dose of blinded study therapy and 705 deaths were observed in all randomized participants, up to June 2015 (approximately 48 months post study start) | Progression-free survival (PFS) is defined as the time between the date of randomization and the date of tumor progression per Modified World Health Organization (mWHO) criteria or death, whichever occurs first. A participant who died without reported progression per mWHO criteria were considered to have progressed on the date of death. For participants who remain alive and have not progressed, PFS was censored on the date of last evaluable tumor assessment. For participants who remain alive and have 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, Denmark, France, Germany, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Mexico, Netherlands, Peru, Poland, Portugal, Romania, Russia, Singapore, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Thailand, United Kingdom, United States
Participant flow
Pre-assignment details
1289 participants were enrolled and 956 were randomized (479 Ipilimumab, 477 Placebo). 948 were treated (475 Ipilimumab, 473 Placebo). Reasons for non-treatment is 4 no longer met study criteria, 2 adverse events unrelated to study drug, 1 participant request to discontinue, and 1 other.
Participants by arm
| Arm | Count |
|---|---|
| Ipilimumab With Paclitaxel/Carboplatin Ipilimumab + Active Chemo Backbone The blinded therapy (Ipilimumab) started at the 3rd dose of active chemotherapy backbone (Paclitaxel/Carboplatin). Ipilimumab: IV solution, intravenous (IV), 10 mg/kg, 90 minute infusion, Once every 3 weeks for 4 doses and then every 12 weeks until disease progression (for a maximum treatment period of 3 years from the first dose) Active Chemo Backbone: Paclitaxel: IV solution, IV, 175 mg/m², 3 hour infusion, Once every 3 weeks for 6 doses Carboplatin: IV solution, IV, Area Under the Curve (AUC) = 6, 30 minute infusion, Once every 3 weeks for 6 doses | 388 |
| Placebo With Paclitaxel/Carboplatin Placebo + Active Chemo Backbone The blinded therapy (Placebo) started at the 3rd dose of active chemotherapy backbone (Paclitaxel/Carboplatin). Placebo: IV solution, IV, 0.9% sodium chloride or 5% dextrose, 90 minute infusion, Once every 3 weeks for 4 doses and then every 12 weeks until disease progression (for a maximum treatment period of 3 years from the first dose) Active Chemo Backbone: Paclitaxel: IV solution, IV, 175 mg/m², 3 hour infusion, Once every 3 weeks for 6 doses Carboplatin: IV solution, IV, Area Under the Curve (AUC) = 6, 30 minute infusion, Once every 3 weeks for 6 doses | 361 |
| Total | 749 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Randomized | Adverse Event Unrelated to Study Drug | 18 | 18 |
| Randomized | Death | 5 | 7 |
| Randomized | Progressive Disease | 41 | 61 |
| Randomized | Randomized but not Treated | 4 | 4 |
| Randomized | Study Drug Toxicity | 13 | 14 |
| Randomized | Subject No Longer Met Study Criteria | 1 | 1 |
| Randomized | Undisclosed Reasons | 1 | 0 |
| Randomized | Withdrawal by Subject | 8 | 11 |
| Treated With Blinded Therapy | Administrative Reason by Sponsor | 1 | 3 |
| Treated With Blinded Therapy | Adverse Event Unrelated to Study Drug | 36 | 14 |
| Treated With Blinded Therapy | Death | 11 | 3 |
| Treated With Blinded Therapy | Investigator's assessment | 1 | 0 |
| Treated With Blinded Therapy | Maximum Clinical Benefit | 2 | 4 |
| Treated With Blinded Therapy | Not Reported | 0 | 2 |
| Treated With Blinded Therapy | Participant hospitalized | 1 | 0 |
| Treated With Blinded Therapy | Participant refused participation | 1 | 0 |
| Treated With Blinded Therapy | Participant started radiotherapy | 1 | 0 |
| Treated With Blinded Therapy | Physician and Patient decision | 1 | 3 |
| Treated With Blinded Therapy | PI decision to discontinue | 0 | 1 |
| Treated With Blinded Therapy | Poor/Non-Compliance | 1 | 2 |
| Treated With Blinded Therapy | Progressive Disease | 223 | 305 |
| Treated With Blinded Therapy | Study Drug Toxicity | 87 | 14 |
| Treated With Blinded Therapy | Subject No Longer Met Study Criteria | 1 | 0 |
| Treated With Blinded Therapy | Withdrawal by Subject | 20 | 7 |
| Treated With Blinded Therapy | Worsening of general condition | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Placebo With Paclitaxel/Carboplatin | Ipilimumab With Paclitaxel/Carboplatin |
|---|---|---|---|
| Age, Continuous | 63.7 years STANDARD_DEVIATION 8.47 | 63.7 years STANDARD_DEVIATION 8.7 | 63.7 years STANDARD_DEVIATION 8.27 |
| Disease Stage at Study Entry Recurrent | 49 Participants | 28 Participants | 21 Participants |
| Disease Stage at Study Entry Stage IV | 700 Participants | 333 Participants | 367 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 | 259 Participants | 124 Participants | 135 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 | 485 Participants | 234 Participants | 251 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 2 | 4 Participants | 3 Participants | 1 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 3 | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 214 Participants | 108 Participants | 106 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 3 Participants | 3 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 | 9 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) White | 519 Participants | 243 Participants | 276 Participants |
| Sex: Female, Male Female | 114 Participants | 52 Participants | 62 Participants |
| Sex: Female, Male Male | 635 Participants | 309 Participants | 326 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 359 / 475 | 371 / 473 |
| other Total, other adverse events | 437 / 475 | 428 / 473 |
| serious Total, serious adverse events | 300 / 475 | 235 / 473 |
Outcome results
Primary
Overall Survival (OS) in Participants Who Received at Least One Dose of Blinded Study Therapy at Primary Endpoint
Overall Survival (OS) was defined as the time from randomization to the date of death. Participants that had not died were censored at last known date alive. Median OS time was calculated using Kaplan-Meier Estimates. Analysis for the Primary Endpoint occurred when the following 2 conditions were both met: (1) 518 deaths were observed in randomized participants treated with at least one dose of blinded study therapy and (2) 705 deaths were observed in all randomized participants.
Time frame: Randomization until 518 deaths were observed in randomized participants treated with at least one dose of blinded study therapy and 705 deaths were observed in all randomized participants, up to June 2015 (approximately 48 months post study start)
Population: All treated participants who received at least one dose of blinded therapy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ipilimumab With Paclitaxel/Carboplatin | Overall Survival (OS) in Participants Who Received at Least One Dose of Blinded Study Therapy at Primary Endpoint | 13.37 months |
| Placebo With Paclitaxel/Carboplatin | Overall Survival (OS) in Participants Who Received at Least One Dose of Blinded Study Therapy at Primary Endpoint | 12.42 months |
Comparison: Hazard ratio = Ipilimumab with Paclitaxel/Carboplatin over Placebo with Paclitaxel/Carboplatinp-value: 0.251795% CI: [0.767, 1.072]Log Rank
Secondary
Median Number of Months With Progression Free Survival (PFS) Per mWHO in Participants Who Have Received at Least One Dose of Blinded Study Therapy at Primary Endpoint
Progression-free survival (PFS) is defined as the time between the date of randomization and the date of tumor progression per Modified World Health Organization (mWHO) criteria or death, whichever occurs first. A participant who died without reported progression per mWHO criteria were considered to have progressed on the date of death. For participants who remain alive and have not progressed, PFS was censored on the date of last evaluable tumor assessment. For participants who remain alive and have no recorded post-baseline tumor assessment, PFS was censored on the day of randomization.
Time frame: Randomization until 518 deaths were observed in randomized participants treated with at least one dose of blinded study therapy and 705 deaths were observed in all randomized participants, up to June 2015 (approximately 48 months post study start)
Population: All treated participants who received at least one dose of blinded therapy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ipilimumab With Paclitaxel/Carboplatin | Median Number of Months With Progression Free Survival (PFS) Per mWHO in Participants Who Have Received at Least One Dose of Blinded Study Therapy at Primary Endpoint | 5.55 months |
| Placebo With Paclitaxel/Carboplatin | Median Number of Months With Progression Free Survival (PFS) Per mWHO in Participants Who Have Received at Least One Dose of Blinded Study Therapy at Primary Endpoint | 5.59 months |
Comparison: Hazard ratio = Ipilimumab with Paclitaxel/Carboplatin over Placebo with Paclitaxel/Carboplatinp-value: 0.067895% CI: [0.749, 1.009]Log Rank
Secondary
Overall Survival (OS) in All Randomized Participants at Primary Endpoint
Overall Survival (OS) was defined as the time from randomization to the date of death. Participants that had not died were censored at last known date alive. Median OS time was calculated using Kaplan-Meier Estimates. Analysis for the Primary Endpoint occurred when the following 2 conditions were both met: (1) 518 deaths were observed in randomized participants treated with at least one dose of blinded study therapy and (2) 705 deaths were observed in all randomized participants.
Time frame: Randomization until 518 deaths were observed in randomized participants treated with at least one dose of blinded study therapy and 705 deaths were observed in all randomized participants, up to June 2015 (approximately 48 months post study start)
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ipilimumab With Paclitaxel/Carboplatin | Overall Survival (OS) in All Randomized Participants at Primary Endpoint | 10.94 months |
| Placebo With Paclitaxel/Carboplatin | Overall Survival (OS) in All Randomized Participants at Primary Endpoint | 10.74 months |
Comparison: Hazard ratio = Ipilimumab with Paclitaxel/Carboplatin over Placebo with Paclitaxel/Carboplatinp-value: 0.242195% CI: [0.792, 1.061]Log Rank