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
PRIMARY OBJECTIVES:
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)
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, 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.
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.
Interventional
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
Yes
Jonas De Souza
Principal Investigator
Cancer and Leukemia Group B
United States: Food and Drug Administration
NCI-2012-02009
NCT01711541
October 2012
Name | Location |
---|---|
University of Chicago Comprehensive Cancer Center | Chicago, Illinois 60637-1470 |
Cancer and Leukemia Group B | Chicago, Illinois 60606 |