TPF Induction Chemotherapy and ABT-888 (Veliparib) - a Phase 1/Randomized Phase 2 Study in Patients With Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck
I. Determine the maximum tolerated dose (MTD), recommended phase II dose, dose limiting
toxicity (DLT), and safety of ABT-888 (veliparib) with cisplatin, 5FU (fluorouracil), and a
taxane (TPF) 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 consisting of TPF with and without ABT-888 in LAHNC. (Phase II)
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, docetaxel
intravenously (IV) over 60 minutes on day 2, cisplatin IV over 60 minutes on day 2, and
fluorouracil IV continuously over 120 hours on days 2-6. 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, docetaxel, cisplatin, and fluorouracil as in Phase I.
Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or
unacceptable toxicity. Patients then continue on to concomitant chemoradiotherapy.
ARM II: Patients receive placebo PO BID on days 1-7. Patients also receive docetaxel,
cisplatin, and fluorouracil as in Phase I. Treatment repeats every 3 weeks for 2 courses in
the absence of disease progression or unacceptable toxicity. Patients then continue on to
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.
CONCOMITANT CHEMORADIATION WITH CISPLATIN: Patients receive cisplatin IV on days 1 and 22 or
2 and 23 and undergo radiation therapy five days a week for 6 weeks.
CONCOMITANT CHEMORADIATION WITH TFHX: Patients receive hydroxyurea PO every 12 hours on days
1-6 (11 doses), fluorouracil IV over 120 hours on days 2-6, paclitaxel IV on day 2, and
undergo radiation therapy BID on days 2-6. Treatment repeats every 2 weeks for 5 courses.
After completion of study treatment, patients are followed up at 2 weeks, 1 and 3 months,
every 3 months for 2 years, every 6 months for 1 year, and then annually for 2 years.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
MTD of veliparib, graded according to the Common Terminology Criteria for Adverse Events (NCI CTCAE) (Phase I)
Up to 3 weeks
Jonas De Souza
Cancer and Leukemia Group B
United States: Food and Drug Administration
|University of Chicago Comprehensive Cancer Center||Chicago, Illinois 60637-1470|
|Cancer and Leukemia Group B||Chicago, Illinois 60606|