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

NCT01711541

Description:

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.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • Oropharyngeal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

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

Title

  • Brief Title: Combination Chemotherapy With or Without Veliparib in Treating Patients With Stage IV Head and Neck Cancer
  • Official Title: 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
  • Clinical Trial IDs

    NCT ID: NCT01711541

    ORG ID: NCI-2012-02009

    NCI ID: NCI-2012-02009

    Trial Conditions

    Human Papillomavirus Infection

    Salivary Gland Squamous Cell Carcinoma

    Stage IVA Hypopharyngeal Squamous Cell Carcinoma

    Stage IVA Laryngeal Squamous Cell Carcinoma

    Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma

    Stage IVA Major Salivary Gland Carcinoma

    Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma

    Stage IVA Oropharyngeal Squamous Cell Carcinoma

    Stage IVB Hypopharyngeal Squamous Cell Carcinoma

    Stage IVB Laryngeal Squamous Cell Carcinoma

    Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma

    Stage IVB Major Salivary Gland Carcinoma

    Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma

    Stage IVB Oropharyngeal Squamous Cell Carcinoma

    Tongue Carcinoma

    Trial Interventions

    Drug Synonyms Arms
    Carboplatin Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplat, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo Arm I (veliparib, combination chemotherapy), Arm II (placebo, combination chemotherapy)
    Cisplatin 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 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-FU, AccuSite, Actino-Hermal, Adrucil, Arumel, Cytosafe, Efudex, Efurix, Fiverocil, Fluoro Uracil, Fluoroplex, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Flurox, Ribofluor, Ro 2-9757, Ro-2-9757, Timazin Arm I (veliparib, combination chemotherapy), Arm II (placebo, combination chemotherapy)
    Hydroxyurea 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)
    Paclitaxel Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat Arm I (veliparib, combination chemotherapy), Arm II (placebo, combination chemotherapy)
    Veliparib ABT-888, PARP-1 inhibitor ABT-888 Arm I (veliparib, combination chemotherapy)

    Trial Purpose

    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.

    Detailed Description

    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 (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.

    Trial Arms

    Name Type Description Interventions
    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. Carboplatin, Cisplatin, Fluorouracil, Hydroxyurea, Paclitaxel, 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. Carboplatin, Cisplatin, Fluorouracil, Hydroxyurea, Paclitaxel

    Eligibility Criteria

    Inclusion Criteria:

    - PHASE I:

    - Patients who are treatment nave, 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 nave, 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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    MTD of veliparib, graded according to the Common Terminology Criteria for Adverse Events (Phase I)

    Relative change in tumor size following 2 courses of induction as measured by RECIST (Phase II)

    Secondary Outcome Measures

    Disease-free survival

    DSS

    OS

    PFS

    Time to local or distant progression

    Toxicity rates during induction and overall

    Trial Keywords