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

NCT01711541 | Completed Phase 1 Results

• 5 other identifiers: NCI-2012-02009A091101N01CM62201U10CA180821U10CA031946
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Head and Neck Squamous Cell Carcinoma; Stage IVA Oropharyngeal Carcinoma AJCC v7; Stage IVB Oropharyngeal Carcinoma AJCC v7

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicity (Phase I)

  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.

  Up to 3 weeks

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

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

  From baseline to 6 weeks

Secondary Outcomes (6)

• Toxicity (Phase I and Phase II)

  upt to 5 years

• PFS (Phase II)

  Up to 5 years

• Disease-free Survival (Phase II)

  Up to 5 years

• Time to Local or Distant Progression (Phase II)

  Up to 5 years

• DSS (Phase II)

  Up to 5 years

Study Arms (2)

Arm I (veliparib, combination chemotherapy)

EXPERIMENTAL

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.

Drug: Carboplatin; Drug: Cisplatin; Drug: Fluorouracil; Drug: Hydroxyurea; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Radiation: Radiation Therapy; Drug: Veliparib

Arm II (placebo, combination chemotherapy)

EXPERIMENTAL

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.

Drug: Carboplatin; Drug: Cisplatin; Drug: Fluorouracil; Drug: Hydroxyurea; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Other: Placebo Administration; Radiation: Radiation Therapy

Interventions

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Arm I (veliparib, combination chemotherapy); Arm II (placebo, combination chemotherapy)

Cisplatin DRUG

Given IV

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

Arm I (veliparib, combination chemotherapy); Arm II (placebo, combination chemotherapy)

Fluorouracil DRUG

Given IV

Also known as: 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-Fu, 5FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757

Arm I (veliparib, combination chemotherapy); Arm II (placebo, combination chemotherapy)

Hydroxyurea DRUG

Given PO

Also known as: Droxia, Hydrea, Hydroxycarbamide, Litalir, Onco-Carbide, Oncocarbide, Oxeron, SQ 1089, SQ-1089, Syrea, WR 83799

Arm I (veliparib, combination chemotherapy); Arm II (placebo, combination chemotherapy)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (veliparib, combination chemotherapy); Arm II (placebo, combination chemotherapy)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Arm I (veliparib, combination chemotherapy); Arm II (placebo, combination chemotherapy)

Placebo Administration OTHER

Given PO

Arm II (placebo, combination chemotherapy)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Name of Radiation Therapy Course, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Arm I (veliparib, combination chemotherapy); Arm II (placebo, combination chemotherapy)

Veliparib DRUG

Given PO

Also known as: ABT-888, PARP-1 inhibitor ABT-888

Arm I (veliparib, combination chemotherapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (5)

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, 60201, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Oropharyngeal Neoplasms

Interventions

Carboplatin; Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; Fluorouracil; dehydroftorafur; Hydroxyurea; Paclitaxel; Taxes; Radiotherapy; Radiation; veliparib

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Urea; Amides; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; Therapeutics; Physical Phenomena

Results Point of Contact

• Title: Everett E. Vokes, M.D.
• Organization: Alliance for Clinical Trials in Oncology

evokes@medicine.bsd.uchicago.edu

773-702-9306

Study Officials

• Jonas De Souza

  Alliance for Clinical Trials in Oncology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2012
• First Posted: October 22, 2012
• Study Start: October 22, 2012
• Primary Completion: February 15, 2018
• Study Completion: May 15, 2023
• Last Updated: June 7, 2023
• Results First Posted: June 5, 2019

Record last verified: 2023-06

Locations

US (5)