Neoplasms

All Conditions

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Head and Neck Neoplasms

Oropharyngeal Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Antineoplastic Agents

All Drugs and Chemicals

Antisickling Agents

Paclitaxel

Carboplatin

Fluorouracil

Albumin-Bound Paclitaxel

Cisplatin

Hydroxyurea

Veliparib

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Enzyme Inhibitors

Poly(ADP-ribose) Polymerase Inhibitors

Patients receive veliparib PO BID on days 1-7, paclitaxel 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.

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.

Laboratory Biomarker Analysis

Placebo Administration

Radiation Therapy

Jonas De Souza

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.

Combination Chemotherapy With or Without Veliparib in Treating Patients With Stage IV Head and Neck Cancer

Carboplatin-Paclitaxel 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

Dose Limiting Toxicity (DLTs) will be assessed during the first cycle of induction chemotherapy.

The following events are considered DLTs: Grade 4 neutropenia (ANC \< 500) lasting more than 14 days, Febrile neutropenia, Grade 4 thrombocytopenia, dose delay of greater than 3 weeks due to failure to recover counts, treatment-related grade 3 or grade 4 non-hematological toxicity (excluding alopecia, fatigue, hypersensitivity reaction, nausea, vomiting, constipation, diarrhea, hypokalemia, hypomagnesemia, hypocalcemia, hypophosphatemia, and grade 3 hypertension), a dose delay of greater than 3 weeks for non-hematological toxicity despite replacement of electrolytes, maximum treatment for diarrhea, nausea, vomiting, and hypertension, any drug-related death.

The number of patients reporting a DLT are reported below. The maximum tolerated dose (MTD) will be determined as the highest dose where 1 or fewer out of 6 patients reports a DLT.

Treatment arms will be compared using the nonparametric Wilcoxon rank-sum test.

Adverse Events were collected each cycle during treatment and follow-up according to the CTCAE v4.0 guidelines. The worst graded adverse event was determined for each patient. Below is a table of the number of patients that reported a Grade 3 or Grade 4 or Grade 5 as their worst reported event.

Summarized using the method of Kaplan-Meier, and compared between groups using the log-rank test. Multivariate Cox proportional hazards regression models will be used to further explore group differences adjusting for other prognostic factors, as well as to estimate hazard ratios.

Summarized using cumulative incidence, and will be compared between groups using Gray's test. Multivariate Cox proportional hazards regression models will be used to further explore group differences adjusting for other prognostic factors, as well as to estimate hazard ratios.

National Cancer Institute (NCI)

Adverse events were collected every week during treatment (up to 13 weeks) and then every 6 months during clinical follow-up for a maximum of 5 years from registration. All patients that began study treatment and were assessed for adverse events are included in this analysis. Patients that cancelled or were not evaluated for adverse events were not included.

ABT-888 doses will be given at 200 mg bid for 7 days in combination with TPF Induction.

Dose Level 0

ABT-888 doses will be given at 200 mg bid for 7 days in combination with paclitaxel 100 mg/m2 and carboplatin AUC 6.

Dose Level 0B

ABT-888 doses will be given at 250 mg bid for 7 days in combination with paclitaxel 100 mg/m2 and carboplatin AUC 6.

Dose Level 1

ABT-888 doses will be given at 300 mg bid for 7 days in combination with paclitaxel 100 mg/m2 and carboplatin AUC 6.

Dose Level 2

ABT-888 doses will be given at 350 mg bid for 7 days in combination with paclitaxel 100 mg/m2 and carboplatin AUC 6.

Dose Level 3

ABT-888 doses will be given at 200 mg bid for 7 days in combination with TPF Induction

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Everett E. Vokes, M.D.

ABT-888 doses will be given at 200 mg bid for 7 days in combination with TPF induction.

Dose Level 0 was not included in this outcome due to a change in treatment regimen. On Dose Level 0B, 1 patient was ineligible based on protocol criteria. On dose level 2, 1 patient cancelled prior to treatment, 1 had a dosing error and 1 pt did not complete cycle 1. On Dose Level 3, 1 patient cancelled prior to treatment.

Dose Limiting Toxicity (Phase I)

Patients receive veliparib PO BID on days 1-7, paclitaxel 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.

Carboplatin: Given IV

Cisplatin: Given IV

Fluorouracil: Given IV

Hydroxyurea: Given PO

Laboratory Biomarker Analysis: Correlative studies

Paclitaxel: Given IV

Radiation Therapy: Undergo radiation therapy

Veliparib: Given PO

Arm I (Veliparib, Combination Chemotherapy)

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.

Carboplatin: Given IV

Cisplatin: Given IV

Fluorouracil: Given IV

Hydroxyurea: Given PO

Laboratory Biomarker Analysis: Correlative studies

Paclitaxel: Given IV

Placebo: Given PO

Radiation Therapy: Undergo radiation therapy

Arm II (Placebo, Combination Chemotherapy)

The Phase II portion of this study never opened and no analysis was planned.

Relative Change in Tumor Size as Measured by RECIST (Phase II)

Grade 3 Adverse Event

Grade 4 Adverse Event

Grade 5 Adverse Event

All patients that started protocol treatment and were evaluated for adverse events are included in this analysis. The Phase II portion of the study never opened, and therefore no data was collected.

Toxicity (Phase I and Phase II)

No patients were eligible for this Phase II endpoint. The Phase II portion of this study never opened.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Combination Chemotherapy With or Without Veliparib in Treating Patients With Stage IV Head and Neck Cancer	NCT01711541	Head and Neck S... Stage IVA Oroph... Stage IVB Oroph...	Carboplatin Cisplatin Fluorouracil Hydroxyurea Laboratory Biom... Paclitaxel Placebo Adminis... Radiation Thera... Veliparib	18 Years -	National Cancer Institute (NCI)
Combination Chemotherapy With or Without Veliparib in Treating Patients With Stage IV Head and Neck Cancer	NCT01711541	Head and Neck S... Stage IVA Oroph... Stage IVB Oroph...	Carboplatin Cisplatin Fluorouracil Hydroxyurea Laboratory Biom... Paclitaxel Placebo Adminis... Radiation Thera... Veliparib	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for stage iva oropharyngeal carcinoma ajcc v7