Description:
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.
Title
- Brief Title: 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
- Official Title: A Randomized, Open-Label, Multicenter, Phase 3 Trial Comparing Veliparib Plus Carboplatin and Paclitaxel Versus Investigator's Choice of Standard Chemotherapy in Subjects Receiving First Cytotoxic Chemotherapy for Metastatic or Advanced Non-Squamous Non-Small Cell Lung Cancer (NSCLC) and Who Are Current or Former Smokers
Clinical Trial IDs
- ORG STUDY ID:
M14-359
- SECONDARY ID:
2014-002565-30
- NCT ID:
NCT02264990
Conditions
- Non-squamous Non-small Cell Lung Cancer
Interventions
| Drug | Synonyms | Arms |
|---|
| Paclitaxel | | Investigator's Choice Chemotherapy |
| Carboplatin | | Investigator's Choice Chemotherapy |
| Cisplatin | | Investigator's Choice Chemotherapy |
| Veliparib | ABT-888 | Veliparib + Carboplatin + Paclitaxel |
| Pemetrexed | Alimta | Investigator's Choice Chemotherapy |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Veliparib + Carboplatin + Paclitaxel | Experimental | 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. | - Paclitaxel
- Carboplatin
- Veliparib
- Pemetrexed
|
| Investigator's Choice Chemotherapy | Active Comparator | 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. | - Paclitaxel
- Carboplatin
- Cisplatin
- Pemetrexed
|
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Overall Survival (OS) in the Lung Subtype Panel Positive Subgroup |
| Time Frame: | 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. |
| Safety Issue: | |
| Description: | 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
| Measure: | Progression Free Survival (PFS) in the Lung Subtype Panel Positive Subgroup |
| Time Frame: | 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. |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Objective Response Rate (ORR) in the Lung Subtype Panel Positive Subgroup |
| Time Frame: | 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. |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Overall Survival in All Participants |
| Time Frame: | 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. |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Progression Free Survival (PFS) in All Participants |
| Time Frame: | 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. |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Objective Response Rate (ORR) in All Participants |
| Time Frame: | 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. |
| Safety Issue: | |
| Description: | 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. |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | AbbVie |
Trial Keywords
- veliparib
- carboplatin
- paclitaxel
- cisplatin
- pemetrexed
- Poly Adenosine diphosphate (ADP)-ribose Polymerase (PARP)
- Metastatic
- Non-squamous
- Non-small cell lung cancer
Last Updated
February 26, 2021
