Combination Chemotherapy With or Without Veliparib in Treating Patients With Stage IV Head and Neck Cancer
Combination Chemotherapy With or Without Veliparib in Treating Patients With Stage IV Head and Neck Cancer
This partially randomized phase I/II trial studies the side effects and best dose of
 veliparib when given together with combination chemotherapy and to see how well they work in
 treating patients with stage IV head and neck cancer. Drugs used in chemotherapy, such as
 docetaxel, cisplatin, and fluorouracil, work in different ways to stop the growth of tumor
 cells, either by killing the cells, by stopping them from dividing, or by stopping them from
 spreading. Veliparib may stop the growth of tumor cells by blocking some of the enzymes
 needed for cell growth. It is not yet known whether combination chemotherapy is more
 effective when given with or without veliparib in treating head and neck cancer.
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.
Inclusion Criteria:

 -  PHASE I:

 -  Patients who are treatment naïve, high risk, stage IVa/IVb (all other sites) and
 histologically proven squamous cell carcinoma of the head and neck (SCCHN) with no
 definitive evidence of metastatic disease, excluding patients with oropharynx human
 papillomavirus (HPV)-positive tumors; in summary, those patients eligible are newly
 diagnosed and treatment naive:

 -  Stage IVa-b squamous cell carcinoma other than oropharyngeal cancer (OPC), or

 -  Oropharyngeal cancer (OPC) HPV-negative, stage IVa-b

 -  PHASE II:

 -  Patients who are treatment naïve, high risk, stage IVa/IVb (all other sites)
 histologically proven SCCHN with no definitive evidence of metastatic disease; in
 summary, those patients eligible are:

 -  Stage IVa-b SCCHN other than OPC, or

 -  OPC, HPV-negative, IVa-b, or

 -  OPC, HPV positive, with greater than 10 pack-year smoking history and N2b-N3
 disease

 -  PHASE I AND II:

 -  Patients must have at least one measurable site of disease according to Response
 Evaluation Criteria in Solid Tumors (RECIST) criteria; i.e., patients must have
 measurable disease, defined as at least one lesion that can be accurately measured in
 at least one dimension (longest diameter to be recorded for non-nodal lesions and
 short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm
 with spiral computed tomography (CT) scan magnetic resonance imaging (MRI), or
 calipers by clinical exam

 -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1

 -  Patients must be able to swallow the drug

 -  Ability to understand and the willingness to sign a written informed consent document

 -  Leukocytes >= 3,000/mm^3

 -  Absolute neutrophil count >= 1,500/mm^3

 -  Platelets >= 100,000/mm^3

 -  Total bilirubin =< 1.5 institutional upper limit of normal (ULN)

 -  Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and
 serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x
 institutional ULN as calculated by Cockcroft-Gault

 -  Creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above
 ULN as calculated by Cockcroft-Gault

 -  Patients who are receiving any other investigational agents are not eligible

 -  Patients with active seizure or a history of seizure are not eligible

 -  Patients with a history of allergic reactions attributed to compounds of similar
 chemical or biologic composition to ABT-888 or other agents used in study, including
 Cremophor, carboplatin, paclitaxel, cisplatin, 5-fluorouracil, hydroxyurea, or any
 compounds of similar chemical or biologic composition are not eligible

 -  Patients with impairment of gastrointestinal function or gastrointestinal disease that
 may significantly alter the absorption of ABT-888 (e.g., ulcerative disease,
 uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel
 resection) are not eligible to participate in this study

 -  Patients with uncontrolled intercurrent illness including, but not limited to, ongoing
 or active infection, symptomatic congestive heart failure, unstable angina pectoris,
 cardiac arrhythmia, or psychiatric illness/social situations that would limit
 compliance with study requirements are not eligible to participate in the study

 -  Pregnant women are not eligible to participate in this study; NOTE: women of child
 bearing potential must have a negative serum or urine pregnancy test within 7 days
 prior to treatment

 -  Women of child-bearing potential and men must agree to use adequate contraception
 (hormonal or barrier method of birth control; abstinence) prior to study entry
 and for the duration of study participation; should a woman become pregnant or
 suspect she is pregnant while she or her partner is participating in this study,
 she should inform her treating physician immediately;

 -  Breastfeeding should be discontinued if the mother is treated with ABT-888

 -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
 therapy are not eligible

 -  Patients receiving chronic, systemic treatment with corticosteroids or another
 immunosuppressive agent are not eligible to participate in this study; topical or
 inhaled corticosteroids are allowed

 -  Patients with other malignancies within the past 2 years, except for adequately
 treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin or
 surgically treated early stage solid tumors are ineligible to participate in this
 study