Study Comparing Veliparib Plus Carboplatin and Paclitaxel Versus Investigator's Choice of Standard Chemotherapy in Adults Receiving First Cytotoxic Chemotherapy for Metastatic or Advanced Non-Squamous Non-Small Cell Lung Cancer (NSCLC) and Who Are Current or Former Smokers
- Conditions
- Non-squamous Non-small Cell Lung Cancer
- Interventions
- Registration Number
- NCT02264990
- Lead Sponsor
- AbbVie
- Brief Summary
The purpose of this study is to evaluate the safety and efficacy of veliparib plus carboplatin and paclitaxel versus the Investigator's choice of standard chemotherapy in adults with metastatic or advanced non-squamous non-small cell lung cancer.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 595
- Subject must be ≥ 18 years of age with life expectancy > 12 weeks.
- Subject must have cytologically or histologically confirmed advanced or metastatic non-squamous NSCLC and are current or former smokers.
- Subject must have NSCLC that is not amenable to surgical resection or radiation with curative intent at time of screening.
- Subject must have at least 1 unidimensional measurable NSCLC lesion on a computed tomography (CT) scan as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
- Subject has a known hypersensitivity to paclitaxel or to other drugs formulated with polyethoxylated castor oil (Cremophor).
- Subject has a known hypersensitivity to platinum compounds.
- Subject has peripheral neuropathy ≥ grade 2.
- Subject has squamous NSCLC, or an untreated known epidermal growth factor receptor (EGFR) mutation of exon 19 deletion or L858R mutation in exon 21, or a known anaplastic lymphoma kinase (ALK) gene rearrangement.
- Subject has received prior cytotoxic chemotherapy or chemoradiotherapy for NSCLC.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Veliparib + Carboplatin + Paclitaxel Carboplatin Participants received 120 mg veliparib twice a day (BID) on Days -2 to 5 (7 days), carboplatin at an area under the curve (AUC) of 6 mg/mL\*min on Day 1 and paclitaxel 200 mg/m² on Day 1 of each 21-day cycle for a maximum of 6 cycles. After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred. Veliparib + Carboplatin + Paclitaxel Paclitaxel Participants received 120 mg veliparib twice a day (BID) on Days -2 to 5 (7 days), carboplatin at an area under the curve (AUC) of 6 mg/mL\*min on Day 1 and paclitaxel 200 mg/m² on Day 1 of each 21-day cycle for a maximum of 6 cycles. After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred. Investigator's Choice Chemotherapy Paclitaxel Participants received Investigator's choice of standard doublet chemotherapy consisting of 1 of the following 3 options, administered on Day 1 of each 21-day cycle for a maximum of 6 cycles: * Carboplatin AUC 6 mg/mL\*min + paclitaxel 200 mg/m² * Cisplatin 75 mg/m² + pemetrexed 500 mg/m² * Carboplatin AUC 6 or AUC 5 mg/mL\*min + pemetrexed 500 mg/m² After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred. Veliparib + Carboplatin + Paclitaxel Pemetrexed Participants received 120 mg veliparib twice a day (BID) on Days -2 to 5 (7 days), carboplatin at an area under the curve (AUC) of 6 mg/mL\*min on Day 1 and paclitaxel 200 mg/m² on Day 1 of each 21-day cycle for a maximum of 6 cycles. After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred. Veliparib + Carboplatin + Paclitaxel Veliparib Participants received 120 mg veliparib twice a day (BID) on Days -2 to 5 (7 days), carboplatin at an area under the curve (AUC) of 6 mg/mL\*min on Day 1 and paclitaxel 200 mg/m² on Day 1 of each 21-day cycle for a maximum of 6 cycles. After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred. Investigator's Choice Chemotherapy Carboplatin Participants received Investigator's choice of standard doublet chemotherapy consisting of 1 of the following 3 options, administered on Day 1 of each 21-day cycle for a maximum of 6 cycles: * Carboplatin AUC 6 mg/mL\*min + paclitaxel 200 mg/m² * Cisplatin 75 mg/m² + pemetrexed 500 mg/m² * Carboplatin AUC 6 or AUC 5 mg/mL\*min + pemetrexed 500 mg/m² After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred. Investigator's Choice Chemotherapy Pemetrexed Participants received Investigator's choice of standard doublet chemotherapy consisting of 1 of the following 3 options, administered on Day 1 of each 21-day cycle for a maximum of 6 cycles: * Carboplatin AUC 6 mg/mL\*min + paclitaxel 200 mg/m² * Cisplatin 75 mg/m² + pemetrexed 500 mg/m² * Carboplatin AUC 6 or AUC 5 mg/mL\*min + pemetrexed 500 mg/m² After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred. Investigator's Choice Chemotherapy Cisplatin Participants received Investigator's choice of standard doublet chemotherapy consisting of 1 of the following 3 options, administered on Day 1 of each 21-day cycle for a maximum of 6 cycles: * Carboplatin AUC 6 mg/mL\*min + paclitaxel 200 mg/m² * Cisplatin 75 mg/m² + pemetrexed 500 mg/m² * Carboplatin AUC 6 or AUC 5 mg/mL\*min + pemetrexed 500 mg/m² After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) in the Lung Subtype Panel Positive Subgroup From randomization up to the data cut-off date of 15 July 2019; median follow-up time was 44.5 and 45.3 months in LSP+ participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively. Overall survival is defined as the time from the date that the participant was randomized to the date of the participant's death. Overall survival was estimated using Kaplan-Meier methodology. Participants still alive at the data cut-off date were censored at the date they were last known to be alive.
- Secondary Outcome Measures
Name Time Method Overall Survival in All Participants From randomization up to the data cut-off date of 15 July 2019; the median OS follow-up time was 45.4 and 44.6 months in all participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively. Overall survival is defined as the time from the date that the participant was randomized to the date of the participant's death. OS was estimated using Kaplan-Meier methodology. Participants still alive at the data cut-off date were censored at the date they were last known to be alive.
Progression Free Survival (PFS) in the Lung Subtype Panel Positive Subgroup From randomization up to the data cut-off date of 15 July 2019; the median follow-up time was 44.5 and 45.3 months in LSP+ participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively. Progression-free survival is defined as the time from the date of randomization to the date of disease progression (PD) per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 or death (all causes of mortality), whichever occurred first.
PD: At least a 20% increase in the size of target lesions, taking as reference the smallest size recorded since the treatment started (Baseline or after) with an absolute increase of at least 5 mm, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions.
PFS was estimated using Kaplan-Meier methodology. Participants who did not have an event of disease progression or had not died on or before the cutoff date were censored at the date of their last disease progression assessment on or before the cut-off date. Any PD and death occurring \> 26 weeks and \> 12 weeks after the previous assessment, respectively, were excluded and patients were censored at last assessment before PD or death.Objective Response Rate (ORR) in the Lung Subtype Panel Positive Subgroup Assessed on Day 1 of Cycles 3 and 5 then every 9 weeks for 1 year or until maintenance therapy was discontinued, then every 12 weeks until radiographic progression or death; median time on follow-up was 5.2 and 6.3 months in each group, respectively. Objective response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria. Response must have been confirmed at a consecutive assessment 28 days or more after the assessment at which response was first observed.
CR: The disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.
PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters, persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits, or any new lesions.Objective Response Rate (ORR) in All Participants Assessed on Day 1 of Cycles 3 and 5 then every 9 weeks for 1 year or until maintenance therapy was discontinued, then every 12 weeks until radiographic progression or death; median time on follow-up was 6.7 and 5.9 months in each group, respectively. Objective response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) per RECIST version 1.1 criteria. Response must have been confirmed at a consecutive assessment 28 days or more after the assessment at which response was first observed.
CR: The disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.
PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters, persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits, or any new lesions.Progression Free Survival (PFS) in All Participants From randomization up to the data cut-off date of 15 July 2019; the median follow-up time was 45.4 and 44.6 months in all participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively. Progression-free survival is defined as the time from the date of randomization to the date of disease progression (PD) per RECIST version 1.1 or death (all causes of mortality), whichever occurred first.
PD: At least a 20% increase in the size of target lesions, taking as reference the smallest size recorded since the treatment started (Baseline or after) with an absolute increase of at least 5 mm, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions.
PFS was estimated using Kaplan-Meier methodology. Participants who did not have an event of disease progression or had not died on or before the cut-off date were censored at the date of their last disease progression assessment on or before the cut-off date. Any PD and death occurring \> 26 weeks and \> 12 weeks after the previous assessment, respectively, were excluded and patients were censored at last assessment before PD or death.
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Trial Locations
- Locations (140)
Clearview Cancer Institute /ID# 131434
🇺🇸Huntsville, Alabama, United States
University of South Alabama /ID# 131518
🇺🇸Mobile, Alabama, United States
Highlands Oncology Group /ID# 131250
🇺🇸Springdale, Arkansas, United States
CBCC Global Research, Inc. at /ID# 132709
🇺🇸Bakersfield, California, United States
California Cancer Assoc. R&E /ID# 131392
🇺🇸Encinitas, California, United States
California Cancer Assoc. R&E /ID# 131949
🇺🇸Encinitas, California, United States
LA Hem-Oncology Med Group /ID# 131639
🇺🇸Los Angeles, California, United States
St Jude Hospital dba St Joseph /ID# 132943
🇺🇸Santa Rosa, California, United States
Icri /Id# 132942
🇺🇸Whittier, California, United States
University of Florida - Archer /ID# 132408
🇺🇸Gainesville, Florida, United States
Scroll for more (130 remaining)Clearview Cancer Institute /ID# 131434🇺🇸Huntsville, Alabama, United States