PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose (MTD), recommended phase II dose, dose limiting
toxicity (DLT), and safety of ABT-888 (veliparib) with carboplatin and paclitaxel induction
chemotherapy in locoregionally advanced head and neck (LAHNC) patients. (Phase I) II. Compare
magnitude of tumor shrinkage (response) following 2 cycles of induction chemotherapy with and
without ABT-888 in LAHNC. (Phase II)
SECONDARY OBJECTIVES:
I. Compare progression-free (PFS), disease-specific (DSS), and overall survival (OS) in
subjects treated with or without ABT-888. (Phase II)
OUTLINE: This is a phase I, dose-escalation study of veliparib followed by a phase II study.
PHASE I: Patients receive veliparib orally (PO) twice daily (BID) on days 1-7, paclitaxel
intravenously (IV) over 60 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes
on day 1. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression
or unacceptable toxicity. Patients then continue on to concomitant chemoradiotherapy.
PHASE II: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive veliparib, paclitaxel, and carboplatin as in Phase I. Treatment
repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable
toxicity. Within 10 days from completion of course 2, patients begin concomitant
chemoradiotherapy.
ARM II: Patients receive placebo PO BID on days 1-7. Patients also receive paclitaxel and
carboplatin as in Phase I. Treatment repeats every 3 weeks for 2 courses in the absence of
disease progression or unacceptable toxicity. Within 10 days from completion of course 2,
patients begin concomitant chemoradiotherapy.
CONCOMITANT CHEMORADIOTHERAPY: Patients are assigned to 1 of 2 regimens of concomitant
chemoradiotherapy based on the guidelines of the institution where they are being treated.
OPTION I (CONCOMITANT CHEMORADIATION WITH CISPLATIN): Patients receive cisplatin IV on days 1
and 22 and undergo radiation therapy 5 days per week for 6 weeks. Treatment repeats every 2
weeks for 5 courses.
OPTION II (CONCOMITANT CHEMORADIATION WITH TFHX): Patients receive hydroxyurea PO every 12
hours on days 1-5 for up to 11 doses, fluorouracil IV over 120 hours on days 1-5, paclitaxel
IV on day 1, and undergo radiation therapy BID on days 1-5. Treatment repeats every 2 weeks
for 5 courses.
After completion of study treatment, patients are followed up at 2 weeks, 1, 3, 6, 12, 18,
24, 30, 36, 48, and 60 months. Patients who progress will be followed up every 6 months
through year 5.