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)

NCT02412371 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: M14-3602016-001659-32
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 12

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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

  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 Outcomes (1)

• Objective Response Rate

  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.

Study Arms (4)

Phase 1: Veliparib + Carboplatin + Paclitaxel + Radiotherapy

EXPERIMENTAL

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.

Drug: Paclitaxel; Drug: Carboplatin; Drug: Veliparib; Radiation: Radiotherapy

Phase 2: Veliparib + CRT -> Paclitaxel/Carboplatin/Veliparib

EXPERIMENTAL

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.

Drug: Paclitaxel; Drug: Carboplatin; Drug: Veliparib; Radiation: Radiotherapy

Phase 2: Veliparib + CRT -> Paclitaxel/Carboplatin/Placebo

EXPERIMENTAL

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.

Drug: Paclitaxel; Drug: Placebo for Veliparib; Drug: Carboplatin; Drug: Veliparib; Radiation: Radiotherapy

Phase 2: Placebo + CRT -> Paclitaxel/Carboplatin/Placebo

ACTIVE COMPARATOR

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.

Drug: Paclitaxel; Drug: Placebo for Veliparib; Drug: Carboplatin; Radiation: Radiotherapy

Interventions

Paclitaxel DRUG

Administered via intravenous infusion on Day 1 of each treatment week (concurrent CRT) / cycle (consolidation)

Phase 1: Veliparib + Carboplatin + Paclitaxel + Radiotherapy; Phase 2: Placebo + CRT -> Paclitaxel/Carboplatin/Placebo; Phase 2: Veliparib + CRT -> Paclitaxel/Carboplatin/Placebo; Phase 2: Veliparib + CRT -> Paclitaxel/Carboplatin/Veliparib

Placebo for Veliparib DRUG

Capsule for oral administration

Phase 2: Placebo + CRT -> Paclitaxel/Carboplatin/Placebo; Phase 2: Veliparib + CRT -> Paclitaxel/Carboplatin/Placebo

Carboplatin DRUG

Administered via intravenous infusion on Day 1 of each treatment week (concurrent CRT) / cycle (consolidation)

Phase 1: Veliparib + Carboplatin + Paclitaxel + Radiotherapy; Phase 2: Placebo + CRT -> Paclitaxel/Carboplatin/Placebo; Phase 2: Veliparib + CRT -> Paclitaxel/Carboplatin/Placebo; Phase 2: Veliparib + CRT -> Paclitaxel/Carboplatin/Veliparib

Veliparib DRUG

Capsule for oral administration

Also known as: ABT-888

Phase 1: Veliparib + Carboplatin + Paclitaxel + Radiotherapy; Phase 2: Veliparib + CRT -> Paclitaxel/Carboplatin/Placebo; Phase 2: Veliparib + CRT -> Paclitaxel/Carboplatin/Veliparib

Radiotherapy RADIATION

Radiation treatment with total dose of 60 - 63 Gy administered on Days 1 to 5 of each week for 7 weeks

Phase 1: Veliparib + Carboplatin + Paclitaxel + Radiotherapy; Phase 2: Placebo + CRT -> Paclitaxel/Carboplatin/Placebo; Phase 2: Veliparib + CRT -> Paclitaxel/Carboplatin/Placebo; Phase 2: Veliparib + CRT -> Paclitaxel/Carboplatin/Veliparib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead

Study Sites (12)

Ucsd /Id# 133037

La Jolla, California, 92093, United States

Location

Christiana Care Health Service /ID# 133486

Newark, Delaware, 19713, United States

Location

University of Chicago /ID# 133828

Chicago, Illinois, 60637-1443, United States

Location

Univ Maryland School Medicine /ID# 132944

Baltimore, Maryland, 21201, United States

Location

Dana-Farber Cancer Institute /ID# 133494

Boston, Massachusetts, 02215, United States

Location

SUNY Upstate Medical University - Downtown /ID# 133492

Syracuse, New York, 13210, United States

Location

Unc /Id# 133496

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center /ID# 133497

Durham, North Carolina, 27710-3000, United States

Location

Wake Forest Univ HS /ID# 134608

Winston-Salem, North Carolina, 27157, United States

Location

Rhode Island Hospital /ID# 133493

Providence, Rhode Island, 02903, United States

Location

The Miriam Hospital /ID# 133910

Providence, Rhode Island, 02906, United States

Location

University of Virginia /ID# 133495

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Paclitaxel; veliparib; Carboplatin; Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Therapeutics

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

abbvieclinicaltrials@abbvie.com

800-633-9110

Study Officials

• AbbVie Inc.

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 6, 2014
• First Posted: April 9, 2015
• Study Start: April 30, 2015
• Primary Completion: August 5, 2019
• Study Completion: August 5, 2019
• Last Updated: July 22, 2020
• Results First Posted: July 22, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• 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.

Locations

US (12)