Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Poly(ADP-ribose) Polymerase Inhibitors

Veliparib

Tubulin Modulators

Antimitotic Agents

Enzyme Inhibitors

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.

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

Placebo for Veliparib

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

Radiotherapy

AbbVie Inc.

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.

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.

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.

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.

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)

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)

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.

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

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.

AbbVie

Participants received 60 mg veliparib BID 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 CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID with carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle.

Veliparib 60 mg BID + CRT -> Veliparib 120 mg BID + CT

Participants received 80 mg veliparib BID 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 CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID with carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle.

Veliparib 80 mg BID + CRT -> Veliparib 120 mg BID + CT

Participants received 120 mg veliparib BID 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 CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID with carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle.

Veliparib 120 mg BID + CRT -> Veliparib 120 mg BID + CT

Participants received 200 mg veliparib BID 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 CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle.

Veliparib 200 mg BID + CRT -> Veliparib 120 mg BID + CT

Participants received 240 mg veliparib BID 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 CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID with carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle.

Veliparib 240 mg BID + CRT -> Veliparib 120 mg BID + CT

Participants received 240 mg veliparib BID 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 CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 240 mg BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle.

Veliparib 240 mg BID + CRT -> Veliparib 240 mg BID + CT

Participants received 60 mg veliparib BID 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 CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID with carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle.

Total

Age, Continuous

Age, Customized

Sex: Female, Male

Race/Ethnicity, Customized

ECOG performance status is used by doctors and researchers to assess how a participant's disease is progressing, assess how the disease affects the daily living activities of the participant and determine appropriate treatment and prognosis.

* 0 = Fully Active (Most Favorable Activity);
* 1 = Restricted activity but ambulatory;
* 2 = Ambulatory but unable to carry out work activities;
* 3 = Limited Self-Care;
* 4 = Completely Disabled, No self-care (Least Favorable Activity)

Eastern Cooperative Oncology Group (ECOG) Performance Score

Global Medical Services

Participants who received at least 1 dose of veliparib

Number of Participants With Dose-limiting Toxicities (DLTs)

Participants who received at least 1 dose of veliparib and with at least one post-baseline tumor assessment

Objective Response Rate

Progression-free survival (PFS) was defined as the time from first dose of study drug to the date of earliest radiographic disease progression per investigator assessment based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death, and was calculated using Kaplan-Meier methods. All radiographic disease progression was included regardless whether the event occurred while the participant was taking study drug or had previously discontinued study drug. Participants who did not experience radiographic disease progression or death were censored at the date of the last disease assessment. Participants with no post-baseline disease assessment were censored at first dose date plus 1 day.

Progressive disease (PD) was defined as at least a 20% increase in the size of target lesions with an absolute increase of at least 5 mm, unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions.

Participants received veliparib twice daily (BID) 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 CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 or 240 mg BID with carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle.

All participants who received veliparib; PFS was pre-specified in the Protocol as a primary endpoint in Phase 2, which was not conducted. For Phase 1 PFS was not a pre-specified endpoint, and was only analyzed for all treatment cohorts combined due to the small sample sizes within each cohort.

Progression-free Survival

Overall survival (OS) was defined as the time from the participant's first dose of study drug to the date of death, and was calculated using Kaplan-Meier methods. Participants who did not die were censored at the date of last study visit or the last known date to be alive, whichever was later.

All participants who received veliparib; OS was pre-specified in the Protocol as a secondary endpoint in Phase 2, which was not conducted. For Phase 1 OS was not a pre-specified endpoint, and was only analyzed for all treatment cohorts combined due to the small sample sizes within each cohort.

Overall Survival

Duration of overall response was defined as time from the date of first response (CR or PR) to the earliest documentation of radiographic progressive disease or death due to disease progression, calculated using Kaplan-Meier methods. Participants who did not experience radiographic disease progression or death were censored at the date of the last disease assessment.

Participants who received at least 1 dose of veliparib with at least 1 post-baseline tumor assessment and a confirmed response; DOR was prespecified as a secondary endpoint in Phase 2, which was not conducted. For Phase 1 DOR was not a prespecified endpoint and was only analyzed for all cohorts combined due to the small sample size of each cohort.

Duration of Overall Response (DOR)

Participants received 60 mg veliparib twice daily (BID) 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 (RT) for 7 weeks.

After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID with carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle.

Spots Global Cancer Trial Database for placebo for veliparib