Combination Chemotherapy With or Without Veliparib in Treating Patients With Stage III-IV Head and Neck Cancer
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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 III-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 III Squamous Cell Carcinoma of the Hypopharynx 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 |
- 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.
- 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:
Drug: cisplatin
Given IV
Other Names:
Drug: fluorouracil
Given IV
Other Names:
Radiation: radiation therapy
Undergo radiation therapy
Other Names:
Drug: hydroxyurea
Given PO
Other Names:
Drug: paclitaxel
Given IV
Other Names:
|
|
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:
Drug: cisplatin
Given IV
Other Names:
Drug: fluorouracil
Given IV
Other Names:
Radiation: radiation therapy
Undergo radiation therapy
Other Names:
Drug: hydroxyurea
Given PO
Other Names:
Drug: paclitaxel
Given IV
Other Names:
|
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 |
Inclusion Criteria:
- PHASE I:
Patients who are treatment naive, high risk, stage III (hypopharynx) or patients who are treatment naive, 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 papilloma virus (HPV)-positive tumors; in summary, those patients eligible are newly diagnosed and treatment naive:
- Stage III (hypopharynx), OR
- Stage IVa-b squamous cell carcinoma other than oropharyngeal cancer (OPC), OR
- OPC HPV-negative, stage IVa-b
- PHASE II:
Patients who are treatment naive, high risk, stage III (hypopharynx) or patients who are treatment naive, high risk, stage IVa/IVb (all other sites) and histologically proven SCCHN with no definitive evidence of metastatic disease; in summary, those patients eligible are:
- Stage III (hypopharynx), OR
- Stage IVa-b SCCHN other than oropharyngeal cancer (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 =< 2
- 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| United States, Illinois | |
| Cancer and Leukemia Group B | Recruiting |
| Chicago, Illinois, United States, 60606 | |
| Contact: Jonas De Souza 773-834-1736 jdesouza@medicine.bsd.uchicago.edu | |
| Principal Investigator: Jonas De Souza | |
| University of Chicago Comprehensive Cancer Center | Recruiting |
| Chicago, Illinois, United States, 60637-1470 | |
| Contact: Jonas De Souza 773-834-7424 | |
| Principal Investigator: Jonas De Souza | |
| 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, A091101, U10CA031946, N01CM62201 |
| Study First Received: | October 18, 2012 |
| Last Updated: | April 24, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Tongue Diseases Carcinoma Carcinoma, Squamous Cell Head and Neck Neoplasms Laryngeal Diseases Papilloma Virus Diseases Tongue Neoplasms Carcinoma, Verrucous Salivary Gland Neoplasms Hypopharyngeal Neoplasms Laryngeal Neoplasms Warts Paranasal Sinus Neoplasms Papillomavirus Infections |
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 Salivary Gland Diseases Pharyngeal Neoplasms Otorhinolaryngologic Neoplasms |
ClinicalTrials.gov processed this record on May 19, 2013