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)
NCT ID: NCT02412371
Last Updated: 2020-07-22
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE1/PHASE2
48 participants
INTERVENTIONAL
2015-04-30
2019-08-05
Brief Summary
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* 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.
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Detailed Description
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1. 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
2. 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.
Conditions
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
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.
TREATMENT
NONE
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.
Study Groups
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Phase 1: Veliparib + Carboplatin + Paclitaxel + Radiotherapy
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.
Paclitaxel
Administered via intravenous infusion on Day 1 of each treatment week (concurrent CRT) / cycle (consolidation)
Carboplatin
Administered via intravenous infusion on Day 1 of each treatment week (concurrent CRT) / cycle (consolidation)
Veliparib
Capsule for oral administration
Radiotherapy
Radiation treatment with total dose of 60 - 63 Gy administered on Days 1 to 5 of each week for 7 weeks
Phase 2: Veliparib + CRT -> Paclitaxel/Carboplatin/Veliparib
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.
Paclitaxel
Administered via intravenous infusion on Day 1 of each treatment week (concurrent CRT) / cycle (consolidation)
Carboplatin
Administered via intravenous infusion on Day 1 of each treatment week (concurrent CRT) / cycle (consolidation)
Veliparib
Capsule for oral administration
Radiotherapy
Radiation treatment with total dose of 60 - 63 Gy administered on Days 1 to 5 of each week for 7 weeks
Phase 2: Veliparib + CRT -> Paclitaxel/Carboplatin/Placebo
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.
Paclitaxel
Administered via intravenous infusion on Day 1 of each treatment week (concurrent CRT) / cycle (consolidation)
Placebo for Veliparib
Capsule for oral administration
Carboplatin
Administered via intravenous infusion on Day 1 of each treatment week (concurrent CRT) / cycle (consolidation)
Veliparib
Capsule for oral administration
Radiotherapy
Radiation treatment with total dose of 60 - 63 Gy administered on Days 1 to 5 of each week for 7 weeks
Phase 2: Placebo + CRT -> Paclitaxel/Carboplatin/Placebo
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.
Paclitaxel
Administered via intravenous infusion on Day 1 of each treatment week (concurrent CRT) / cycle (consolidation)
Placebo for Veliparib
Capsule for oral administration
Carboplatin
Administered via intravenous infusion on Day 1 of each treatment week (concurrent CRT) / cycle (consolidation)
Radiotherapy
Radiation treatment with total dose of 60 - 63 Gy administered on Days 1 to 5 of each week for 7 weeks
Interventions
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Paclitaxel
Administered via intravenous infusion on Day 1 of each treatment week (concurrent CRT) / cycle (consolidation)
Placebo for Veliparib
Capsule for oral administration
Carboplatin
Administered via intravenous infusion on Day 1 of each treatment week (concurrent CRT) / cycle (consolidation)
Veliparib
Capsule for oral administration
Radiotherapy
Radiation treatment with total dose of 60 - 63 Gy administered on Days 1 to 5 of each week for 7 weeks
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Participants in the randomized portion of the study must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 criteria.
3. Participants must have V20 (volume of lung to receive 20 Gy radiotherapy according to simulation) \< 35%.
4. Participant must have an Eastern Cooperative Oncology Group (ECOG) performance score of 0 - 1.
5. Participant must have adequate hematologic, renal, hepatic, and lung function.
6. Participant must consent to provide archived tissue or cytology sample of NSCLC lesion for analysis.
Exclusion Criteria
2. Participants with prior exposure to poly-adenosine diphosphate (ADP)-ribose polymerase (PARP) inhibitors.
3. Participants with known hypersensitivity to carboplatin, paclitaxel, or formulations containing polyethoxylated castor oil (Cremophor).
4. Participants with prior mediastinal or thoracic radiotherapy. Prior tangential radiotherapy to prior breast cancer is acceptable.
5. Participants with major surgery in the 4 weeks prior to randomization (Video-assisted thoracoscopic surgery (VATS) and/or mediastinoscopy is not considered major surgery).
6. 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.
7. Participant is pregnant or lactating.
8. 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.
18 Years
ALL
No
Sponsors
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AbbVie
INDUSTRY
Responsible Party
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Principal Investigators
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AbbVie Inc.
Role: STUDY_DIRECTOR
AbbVie
Locations
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Ucsd /Id# 133037
La Jolla, California, United States
Christiana Care Health Service /ID# 133486
Newark, Delaware, United States
University of Chicago /ID# 133828
Chicago, Illinois, United States
Univ Maryland School Medicine /ID# 132944
Baltimore, Maryland, United States
Dana-Farber Cancer Institute /ID# 133494
Boston, Massachusetts, United States
SUNY Upstate Medical University - Downtown /ID# 133492
Syracuse, New York, United States
Unc /Id# 133496
Chapel Hill, North Carolina, United States
Duke University Medical Center /ID# 133497
Durham, North Carolina, United States
Wake Forest Univ HS /ID# 134608
Winston-Salem, North Carolina, United States
Rhode Island Hospital /ID# 133493
Providence, Rhode Island, United States
The Miriam Hospital /ID# 133910
Providence, Rhode Island, United States
University of Virginia /ID# 133495
Charlottesville, Virginia, United States
Countries
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Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
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2016-001659-32
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
M14-360
Identifier Type: -
Identifier Source: org_study_id
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