Back to resultsA Study Evaluating the Efficacy and Tolerability of Veliparib in Combination With Paclitaxel/Carboplatin-Based Chemoradiotherapy Followed by Veliparib and Paclitaxel/Carboplatin Consolidation in Adults With Stage III Non-Small Cell Lung Cancer (NSCLC)
Primary Purpose
Non-small Cell Lung Cancer Stage III
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Paclitaxel
Placebo for Veliparib
Carboplatin
Veliparib
Radiotherapy
Sponsored by
About this trial
This is an interventional treatment trial for Non-small Cell Lung Cancer Stage III focused on measuring veliparib, PARP inhibitor, ABT-888, first line, previously untreated, stage III, non-small cell lung cancer, radiotherapy, paclitaxel, carboplatin
Eligibility Criteria
Inclusion Criteria:
- Participants with histologically or cytologically confirmed Stage III non-small cell lung cancer (NSCLC).
- Participants in the randomized portion of the study must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 criteria.
- Participants must have V20 (volume of lung to receive 20 Gy radiotherapy according to simulation) < 35%.
- Participant must have an Eastern Cooperative Oncology Group (ECOG) performance score of 0 - 1.
- Participant must have adequate hematologic, renal, hepatic, and lung function.
- Participant must consent to provide archived tissue or cytology sample of NSCLC lesion for analysis.
Exclusion Criteria:
- Participants with prior chemotherapy or radiotherapy (RT) for current NSCLC. Participants curatively treated for past early stage NSCLC greater than 3 years ago may be included.
- Participants with prior exposure to poly-adenosine diphosphate (ADP)-ribose polymerase (PARP) inhibitors.
- Participants with known hypersensitivity to carboplatin, paclitaxel, or formulations containing polyethoxylated castor oil (Cremophor).
- Participants with prior mediastinal or thoracic radiotherapy. Prior tangential radiotherapy to prior breast cancer is acceptable.
- Participants with major surgery in the 4 weeks prior to randomization (Video-assisted thoracoscopic surgery (VATS) and/or mediastinoscopy is not considered major surgery).
- Participants with a previous or concurrent malignancy except for treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient received potentially curative treatment and has been disease-free for 3 years or is considered cured by the investigator if has been disease-free for less than 3 years.
- Participant is pregnant or lactating.
- Participant with sensory peripheral neuropathy of ≥ Grade 2 at baseline, unable to swallow medication, or participants with prior history of seizure within the prior 12 months.
Sites / Locations
- Ucsd /Id# 133037
- Christiana Care Health Service /ID# 133486
- University of Chicago /ID# 133828
- Univ Maryland School Medicine /ID# 132944
- Dana-Farber Cancer Institute /ID# 133494
- SUNY Upstate Medical University - Downtown /ID# 133492
- Unc /Id# 133496
- Duke University Medical Center /ID# 133497
- Wake Forest Univ HS /ID# 134608
- Rhode Island Hospital /ID# 133493
- The Miriam Hospital /ID# 133910
- University of Virginia /ID# 133495
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Active Comparator
Arm Label
Phase 1: Veliparib + Carboplatin + Paclitaxel + Radiotherapy
Phase 2: Veliparib + CRT -> Paclitaxel/Carboplatin/Veliparib
Phase 2: Veliparib + CRT -> Paclitaxel/Carboplatin/Placebo
Phase 2: Placebo + CRT -> Paclitaxel/Carboplatin/Placebo
Arm Description
Participants in Phase 1 will be sequentially assigned to ascending dose levels of 60 mg, 80 mg, 120 mg, 200 mg, and 240 mg of twice daily (BID) veliparib in combination with carboplatin at an area under the concentration-time curve (AUC) 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent chemoradiotherapy participants will receive up to 2 cycles of consolidation therapy consisting of veliparib 120 mg or 240 mg BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle.
Participants will receive veliparib at the recommended phase 2 dose determined in Phase 1 in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent chemoradiotherapy participants will receive up to 2 cycles of consolidation therapy consisting of veliparib 120 mg or 240 mg BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle.
Participants will receive veliparib at the recommended phase 2 dose determined in Phase 1 in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent chemoradiotherapy participants will receive up to 2 cycles of consolidation therapy consisting of placebo to veliparib BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle.
Participants will receive placebo to veliparib with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent chemoradiotherapy participants will receive up to 2 cycles of consolidation therapy consisting of placebo to veliparib BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle.
Outcomes
Primary Outcome Measures
Number of Participants With Dose-limiting Toxicities (DLTs)
DLTs were defined as the following events considered treatment-related by the Investigator, graded per Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
Radiation-induced myelopathy/myelitis or ≥ Grade (G) 3 cardiac toxicity
Radiation-related pneumonitis resulting in delay in RT, CT, or veliparib of >3 weeks or early discontinuation (DC) of RT (total dose <50 Gy)
≥G4 esophagitis or esophagitis, dysphagia, and odynophagia requiring treatment interruption of >7 days despite medical management, neutropenia for >7 days or neutropenic fever or thrombocytopenia
≥G2 seizure
G4 diarrhea or nausea/vomiting despite antiemetic therapy for >48 hours
Any other toxicity resulting in delay in RT, CT or veliparib >14 days or early DC of RT
Other nonhematologic toxicities ≥G3, except anorexia, fatigue, G3 infection, G3 aspartate/alanine transferase (AST/ALT) elevations ≤7 days, infusion reactions, G3/4 lymphopenia or electrolyte abnormalities corrected to ≤G2 in <48 hours
Secondary Outcome Measures
Objective Response Rate
Objective response rate (ORR) is defined as the percentage of participants who have a confirmed complete response (CR) or partial response (PR) as assessed by the investigator using RECIST v1.1. Participants who did not meet complete response or partial response, including those who did not have post-baseline radiological assessments were considered as non-responders.
Complete Response (CR): The disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Normalization of tumor marker level. All lymph nodes must be non-pathological in size (< 10 mm short axis).
Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Response must have been confirmed 4 weeks after the first documentation.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02412371
Brief Title
A Study Evaluating the Efficacy and Tolerability of Veliparib in Combination With Paclitaxel/Carboplatin-Based Chemoradiotherapy Followed by Veliparib and Paclitaxel/Carboplatin Consolidation in Adults With Stage III Non-Small Cell Lung Cancer (NSCLC)
Official Title
A Phase 1 Dose Escalation and Phase 2 Randomized, Placebo-Controlled Study of the Efficacy and Tolerability of Veliparib in Combination With Paclitaxel/Carboplatin-Based Chemoradiotherapy Followed by Veliparib and Paclitaxel/Carboplatin Consolidation in Subjects With Stage III Non-Small Cell Lung Cancer (NSCLC)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Terminated
Why Stopped
Phase 2 was not conducted due to a change in the standard of care for newly diagnosed, unresectable Stage III NSCLC
Study Start Date
April 30, 2015 (Actual)
Primary Completion Date
August 5, 2019 (Actual)
Study Completion Date
August 5, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study seeks to establish
the recommended Phase 2 dose (RPTD) of veliparib in combination with concurrent paclitaxel/carboplatin-based chemoradiotherapy (CRT) and consolidation with paclitaxel/carboplatin-based chemotherapy (Phase 1 portion), and
to assess whether the addition of oral veliparib versus placebo to paclitaxel/carboplatin-based chemoradiotherapy with paclitaxel/carboplatin consolidation will improve progression-free survival (PFS) in adults with Stage III non-small cell lung cancer (Phase 2 portion).
A strategy decision was made not to proceed to Phase 2 portion of this study due to change in standard of care.
Detailed Description
This was to be a 2-phase study consisting of
A Phase 1, dose escalation study of veliparib to determine a RPTD for combination with concurrent paclitaxel/carboplatin-based CRT and paclitaxel/carboplatin-based consolidation chemotherapy; followed by
A Phase 2, randomized, double-blinded study to determine whether veliparib improved outcome relative to placebo when added to paclitaxel/carboplatin based CRT followed by consolidation paclitaxel/carboplatin in adults with previously untreated Stage III NSCLC.
In the dose escalation phase (Phase 1) of the study participants will be assigned to ascending doses of veliparib in combination with carboplatin, paclitaxel, and thoracic radiotherapy for 7 weeks following a traditional "3 + 3" design. The first cohort of at least 3 - 6 participants will receive veliparib 60 mg twice a day (BID) throughout CRT. Dose limiting toxicity (DLT) events will be collected for each dosing cohort until a new dosing cohort is opened or until the RPTD is identified. Participants will also receive a consolidation dose of veliparib of 120 mg BID + carboplatin and paclitaxel for up to two 21-day cycles. Once the concurrent CRT RPTD is identified, an additional cohort will be enrolled to explore the tolerability of a consolidation dose of veliparib at 240 mg BID + carboplatin + paclitaxel for up to two 21-day cycles.
Following the dose escalation portion of the study, the RPTD will be determined by the sponsor and the Phase 2 portion of the study will begin with patient randomization in a 1:1:1 ratio to concurrent paclitaxel/carboplatin/radiotherapy/veliparib followed by consolidation paclitaxel/carboplatin/veliparib, concurrent paclitaxel/carboplatin/radiotherapy/veliparib followed by consolidation paclitaxel/carboplatin/placebo, or concurrent paclitaxel/carboplatin/radiotherapy/placebo followed by consolidation paclitaxel/carboplatin/placebo. Randomization will be stratified by tumor volume (≤ 90 versus > 90 cm³) and smoking history (current smoker versus former smoker versus never smoked).
Phase 2 was not carried out since during the study there was a change in standard of care for patients with newly diagnosed, unresectable Stage III NSCLC.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer Stage III
Keywords
veliparib, PARP inhibitor, ABT-888, first line, previously untreated, stage III, non-small cell lung cancer, radiotherapy, paclitaxel, carboplatin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Model Description
In the dose escalation phase (Phase 1) of the study participants will be enrolled sequentially to receive ascending dose of veliparib in combination with carboplatin + paclitaxel + thoracic radiotherapy.
In the Phase 2 portion of the study participants were to be randomized in a 1:1:1 ratio to one of three treatment arms.
Masking
None (Open Label)
Masking Description
All participants will be treated with open-label paclitaxel and carboplatin (Phase 1 and Phase 2).
Participants in Phase 1 will be treated with open-label veliparib. In Phase 2, the Sponsor, Investigator, study site personnel and participant were to be be blinded to each participant's treatment with veliparib or placebo throughout the course of the study.
Allocation
Non-Randomized
Enrollment
48 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Phase 1: Veliparib + Carboplatin + Paclitaxel + Radiotherapy
Arm Type
Experimental
Arm Description
Participants in Phase 1 will be sequentially assigned to ascending dose levels of 60 mg, 80 mg, 120 mg, 200 mg, and 240 mg of twice daily (BID) veliparib in combination with carboplatin at an area under the concentration-time curve (AUC) 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks.
After completion of concurrent chemoradiotherapy participants will receive up to 2 cycles of consolidation therapy consisting of veliparib 120 mg or 240 mg BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle.
Arm Title
Phase 2: Veliparib + CRT -> Paclitaxel/Carboplatin/Veliparib
Arm Type
Experimental
Arm Description
Participants will receive veliparib at the recommended phase 2 dose determined in Phase 1 in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks.
After completion of concurrent chemoradiotherapy participants will receive up to 2 cycles of consolidation therapy consisting of veliparib 120 mg or 240 mg BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle.
Arm Title
Phase 2: Veliparib + CRT -> Paclitaxel/Carboplatin/Placebo
Arm Type
Experimental
Arm Description
Participants will receive veliparib at the recommended phase 2 dose determined in Phase 1 in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks.
After completion of concurrent chemoradiotherapy participants will receive up to 2 cycles of consolidation therapy consisting of placebo to veliparib BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle.
Arm Title
Phase 2: Placebo + CRT -> Paclitaxel/Carboplatin/Placebo
Arm Type
Active Comparator
Arm Description
Participants will receive placebo to veliparib with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks.
After completion of concurrent chemoradiotherapy participants will receive up to 2 cycles of consolidation therapy consisting of placebo to veliparib BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle.
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Intervention Description
Administered via intravenous infusion on Day 1 of each treatment week (concurrent CRT) / cycle (consolidation)
Intervention Type
Drug
Intervention Name(s)
Placebo for Veliparib
Intervention Description
Capsule for oral administration
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
Administered via intravenous infusion on Day 1 of each treatment week (concurrent CRT) / cycle (consolidation)
Intervention Type
Drug
Intervention Name(s)
Veliparib
Other Intervention Name(s)
ABT-888
Intervention Description
Capsule for oral administration
Intervention Type
Radiation
Intervention Name(s)
Radiotherapy
Intervention Description
Radiation treatment with total dose of 60 - 63 Gy administered on Days 1 to 5 of each week for 7 weeks
Primary Outcome Measure Information:
Title
Number of Participants With Dose-limiting Toxicities (DLTs)
Description
DLTs were defined as the following events considered treatment-related by the Investigator, graded per Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
Radiation-induced myelopathy/myelitis or ≥ Grade (G) 3 cardiac toxicity
Radiation-related pneumonitis resulting in delay in RT, CT, or veliparib of >3 weeks or early discontinuation (DC) of RT (total dose <50 Gy)
≥G4 esophagitis or esophagitis, dysphagia, and odynophagia requiring treatment interruption of >7 days despite medical management, neutropenia for >7 days or neutropenic fever or thrombocytopenia
≥G2 seizure
G4 diarrhea or nausea/vomiting despite antiemetic therapy for >48 hours
Any other toxicity resulting in delay in RT, CT or veliparib >14 days or early DC of RT
Other nonhematologic toxicities ≥G3, except anorexia, fatigue, G3 infection, G3 aspartate/alanine transferase (AST/ALT) elevations ≤7 days, infusion reactions, G3/4 lymphopenia or electrolyte abnormalities corrected to ≤G2 in <48 hours
Time Frame
For Cohorts 1 - 5, from the start of veliparib dosing through 28 days after RT completion or until initiation of consolidation CT, approx. 10 weeks; For Cohort 6, 21 days from start of consolidation CT or until the start of cycle 2 consolidation therapy.
Secondary Outcome Measure Information:
Title
Objective Response Rate
Description
Objective response rate (ORR) is defined as the percentage of participants who have a confirmed complete response (CR) or partial response (PR) as assessed by the investigator using RECIST v1.1. Participants who did not meet complete response or partial response, including those who did not have post-baseline radiological assessments were considered as non-responders.
Complete Response (CR): The disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Normalization of tumor marker level. All lymph nodes must be non-pathological in size (< 10 mm short axis).
Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Response must have been confirmed 4 weeks after the first documentation.
Time Frame
Tumor assessments were performed prior to consolidation chemotherapy, 24 weeks after start of treatment, every 8 weeks until 1 year after start of treatment, and then every 12 weeks until disease progression; median time on follow-up was 11 months.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participants with histologically or cytologically confirmed Stage III non-small cell lung cancer (NSCLC).
Participants in the randomized portion of the study must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 criteria.
Participants must have V20 (volume of lung to receive 20 Gy radiotherapy according to simulation) < 35%.
Participant must have an Eastern Cooperative Oncology Group (ECOG) performance score of 0 - 1.
Participant must have adequate hematologic, renal, hepatic, and lung function.
Participant must consent to provide archived tissue or cytology sample of NSCLC lesion for analysis.
Exclusion Criteria:
Participants with prior chemotherapy or radiotherapy (RT) for current NSCLC. Participants curatively treated for past early stage NSCLC greater than 3 years ago may be included.
Participants with prior exposure to poly-adenosine diphosphate (ADP)-ribose polymerase (PARP) inhibitors.
Participants with known hypersensitivity to carboplatin, paclitaxel, or formulations containing polyethoxylated castor oil (Cremophor).
Participants with prior mediastinal or thoracic radiotherapy. Prior tangential radiotherapy to prior breast cancer is acceptable.
Participants with major surgery in the 4 weeks prior to randomization (Video-assisted thoracoscopic surgery (VATS) and/or mediastinoscopy is not considered major surgery).
Participants with a previous or concurrent malignancy except for treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient received potentially curative treatment and has been disease-free for 3 years or is considered cured by the investigator if has been disease-free for less than 3 years.
Participant is pregnant or lactating.
Participant with sensory peripheral neuropathy of ≥ Grade 2 at baseline, unable to swallow medication, or participants with prior history of seizure within the prior 12 months.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
AbbVie Inc.
Organizational Affiliation
AbbVie
Official's Role
Study Director
Facility Information:
Facility Name
Ucsd /Id# 133037
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
Christiana Care Health Service /ID# 133486
City
Newark
State/Province
Delaware
ZIP/Postal Code
19713
Country
United States
Facility Name
University of Chicago /ID# 133828
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637-1443
Country
United States
Facility Name
Univ Maryland School Medicine /ID# 132944
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Dana-Farber Cancer Institute /ID# 133494
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
SUNY Upstate Medical University - Downtown /ID# 133492
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Unc /Id# 133496
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Duke University Medical Center /ID# 133497
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710-3000
Country
United States
Facility Name
Wake Forest Univ HS /ID# 134608
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Rhode Island Hospital /ID# 133493
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Facility Name
The Miriam Hospital /ID# 133910
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02906
Country
United States
Facility Name
University of Virginia /ID# 133495
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
IPD Sharing Time Frame
Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
IPD Sharing Access Criteria
Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
IPD Sharing URL
https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html
Learn more about this trial
A Study Evaluating the Efficacy and Tolerability of Veliparib in Combination With Paclitaxel/Carboplatin-Based Chemoradiotherapy Followed by Veliparib and Paclitaxel/Carboplatin Consolidation in Adults With Stage III Non-Small Cell Lung Cancer (NSCLC)
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