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.
Additional locations may be listed on ClinicalTrials.gov for NCT02412371.
See trial information on ClinicalTrials.gov for a list of participating sites.
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.
