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

This study has suspended participant recruitment.
(Temporarily stopped for assessment. Contact ctsucontact@westat.com for specifics)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01711541
First received: October 18, 2012
Last updated: June 30, 2014
Last verified: February 2014
  Purpose

This partially randomized phase I/II trial studies the side effects and best dose of veliparib when given together with combination chemotherapy and how well they work in treating patients with 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 or stopping them from dividing. 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.


Condition Intervention Phase
Human Papilloma Virus Infection
Salivary Gland Squamous Cell Carcinoma
Stage IV Squamous Cell Carcinoma of the Nasopharynx
Stage IVA Salivary Gland Cancer
Stage IVA Squamous Cell Carcinoma of the Larynx
Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage IVA Squamous Cell Carcinoma of the Oropharynx
Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Stage IVA Verrucous Carcinoma of the Larynx
Stage IVA Verrucous Carcinoma of the Oral Cavity
Stage IVB Salivary Gland Cancer
Stage IVB Squamous Cell Carcinoma of the Larynx
Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage IVB Squamous Cell Carcinoma of the Oropharynx
Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Stage IVB Verrucous Carcinoma of the Larynx
Stage IVB Verrucous Carcinoma of the Oral Cavity
Tongue Cancer
Drug: veliparib
Other: placebo
Drug: docetaxel
Drug: cisplatin
Drug: fluorouracil
Radiation: radiation therapy
Drug: hydroxyurea
Drug: paclitaxel
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • MTD of veliparib, graded according to the Common Terminology Criteria for Adverse Events (NCI CTCAE) (Phase I) [ Time Frame: Up to 3 weeks ] [ Designated as safety issue: Yes ]
  • Relative change in tumor size following 2 courses of induction as measured by RECIST (Phase II) [ Time Frame: From baseline to 6 weeks ] [ Designated as safety issue: No ]
    Treatment arms will be compared using the nonparametric Wilcoxon rank-sum test.


Secondary Outcome Measures:
  • Toxicity rates during induction and overall [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Toxicity rates will be summarized by group, and compared between groups using the chi-squared or Fisher's exact test.

  • PFS [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Summarized using the method of Kaplan-Meier, and compared between groups using the log-rank test.

  • Disease-free survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Summarized using the method of Kaplan-Meier, and compared between groups using the log-rank test.

  • Time to local or distant progression [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Summarized using the method of Kaplan-Meier, and compared between groups using the log-rank test.

  • Disease-specific survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Summarized using cumulative incidence, and will be compared between groups using Gray's test.

  • Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Summarized using the method of Kaplan-Meier, and compared between groups using the log-rank test.


Estimated Enrollment: 110
Study Start Date: October 2012
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (veliparib, combination chemotherapy)
Patients receive veliparib PO BID on days 1-7, docetaxel 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.
Drug: veliparib
Given PO
Other Name: ABT-888
Drug: docetaxel
Given IV
Other Names:
  • RP 56976
  • Taxotere
  • TXT
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Radiation: radiation therapy
Undergo radiation therapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Drug: hydroxyurea
Given PO
Other Names:
  • HU
  • HYD
  • Hydrea
  • Hydroxycarbamide
  • Hydurea
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Experimental: Arm II (placebo, combination chemotherapy)
Patients receive placebo PO BID on days 1-7. Patients also receive docetaxel, cisplatin, and fluorouracil as in Arm 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.
Other: placebo
Given PO
Other Name: PLCB
Drug: docetaxel
Given IV
Other Names:
  • RP 56976
  • Taxotere
  • TXT
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Radiation: radiation therapy
Undergo radiation therapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Drug: hydroxyurea
Given PO
Other Names:
  • HU
  • HYD
  • Hydrea
  • Hydroxycarbamide
  • Hydurea
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol

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 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 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) and histologically proven squamous cell carcinoma of the head and neck (SCCHN) with no definitive evidence of metastatic disease, excluding patients with oropharynx 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 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 =< institutional upper limit of normal (ULN)
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamic pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 X institutional ULN
  • Creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above ULN
  • 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, docetaxel, 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 registration; ABT-888 is a poly adenosine diphosphate ribose (ADP) ribose polymerase (PARP) inhibitor with the potential for teratogenic or abortifacient effects;

    • 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;
    • Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ABT-888, breastfeeding should be discontinued if the mother is treated with ABT-888; these potential risks may also apply to other agents used in this study
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are not eligible because of the potential for pharmacokinetic interactions with ABT-888
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01711541

Locations
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
Sponsors and Collaborators
Investigators
Principal Investigator: Jonas De Souza Cancer and Leukemia Group B
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01711541     History of Changes
Other Study ID Numbers: NCI-2012-02009, NCI-2012-02009, A091101, A091101, U10CA031946, P30CA014236, N01CM62201
Study First Received: October 18, 2012
Last Updated: June 30, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Paranasal Sinus Neoplasms
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Laryngeal Diseases
Papilloma
Virus Diseases
Tongue Neoplasms
Carcinoma, Verrucous
Salivary Gland Neoplasms
Papillomavirus Infections
Laryngeal Neoplasms
Oropharyngeal Neoplasms
Nasopharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Mouth Neoplasms
Mouth Diseases
Stomatognathic Diseases
Tongue Diseases
Salivary Gland Diseases
DNA Virus Infections
Tumor Virus Infections
Otorhinolaryngologic Neoplasms
Respiratory Tract Neoplasms

ClinicalTrials.gov processed this record on August 01, 2014