Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02412371
Recruitment Status : Terminated (Phase 2 was not conducted due to a change in the standard of care for newly diagnosed, unresectable Stage III NSCLC)
First Posted : April 9, 2015
Results First Posted : July 22, 2020
Last Update Posted : July 22, 2020
Sponsor:
Information provided by (Responsible Party):
AbbVie

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.


Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Stage III Drug: Paclitaxel Drug: Placebo for Veliparib Drug: Carboplatin Drug: Veliparib Radiation: Radiotherapy Phase 1 Phase 2

Detailed Description:

This was to be a 2-phase study consisting of

  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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention 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.

Primary Purpose: Treatment
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)
Actual Study Start Date : April 30, 2015
Actual Primary Completion Date : August 5, 2019
Actual Study Completion Date : August 5, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.

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

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

Drug: Veliparib
Capsule for oral administration
Other Name: ABT-888

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

Experimental: 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.

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

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

Drug: Veliparib
Capsule for oral administration
Other Name: ABT-888

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

Experimental: 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.

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

Drug: Placebo for Veliparib
Capsule for oral administration

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

Drug: Veliparib
Capsule for oral administration
Other Name: ABT-888

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

Active Comparator: 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.

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

Drug: Placebo for Veliparib
Capsule for oral administration

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

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




Primary Outcome Measures :
  1. Number of Participants With Dose-limiting Toxicities (DLTs) [ 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. ]

    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 :
  1. Objective Response Rate [ 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. ]

    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.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Participants with histologically or cytologically confirmed Stage III non-small cell lung cancer (NSCLC).
  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:

  1. 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.
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02412371


Locations
Layout table for location information
United States, California
Ucsd /Id# 133037
La Jolla, California, United States, 92093
United States, Delaware
Christiana Care Health Service /ID# 133486
Newark, Delaware, United States, 19713
United States, Illinois
University of Chicago /ID# 133828
Chicago, Illinois, United States, 60637-1443
United States, Maryland
Univ Maryland School Medicine /ID# 132944
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Dana-Farber Cancer Institute /ID# 133494
Boston, Massachusetts, United States, 02215
United States, New York
SUNY Upstate Medical University - Downtown /ID# 133492
Syracuse, New York, United States, 13210
United States, North Carolina
Unc /Id# 133496
Chapel Hill, North Carolina, United States, 27599
Duke University Medical Center /ID# 133497
Durham, North Carolina, United States, 27710-3000
Wake Forest Univ HS /ID# 134608
Winston-Salem, North Carolina, United States, 27157
United States, Rhode Island
Rhode Island Hospital /ID# 133493
Providence, Rhode Island, United States, 02903
The Miriam Hospital /ID# 133910
Providence, Rhode Island, United States, 02906
United States, Virginia
University of Virginia /ID# 133495
Charlottesville, Virginia, United States, 22908
Sponsors and Collaborators
AbbVie
Investigators
Layout table for investigator information
Study Director: AbbVie Inc. AbbVie
  Study Documents (Full-Text)

Documents provided by AbbVie:
Layout table for additonal information
Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT02412371    
Other Study ID Numbers: M14-360
2016-001659-32 ( EudraCT Number )
First Posted: April 9, 2015    Key Record Dates
Results First Posted: July 22, 2020
Last Update Posted: July 22, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (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.
URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html

Layout table for additional information
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
Keywords provided by AbbVie:
veliparib
PARP inhibitor
ABT-888
first line
previously untreated
stage III
non-small cell lung cancer
radiotherapy
paclitaxel
carboplatin
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Paclitaxel
Carboplatin
Veliparib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors