Combination Chemotherapy With or Without Veliparib in Treating Patients With Stage IV Head and Neck Cancer
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| ClinicalTrials.gov Identifier: NCT01711541 |
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Recruitment Status :
Active, not recruiting
First Posted : October 22, 2012
Results First Posted : June 5, 2019
Last Update Posted : January 27, 2023
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Head and Neck Squamous Cell Carcinoma Stage IVA Oropharyngeal Carcinoma AJCC v7 Stage IVB Oropharyngeal Carcinoma AJCC v7 | Drug: Carboplatin Drug: Cisplatin Drug: Fluorouracil Drug: Hydroxyurea Other: Laboratory Biomarker Analysis Drug: Paclitaxel Other: Placebo Administration Radiation: Radiation Therapy Drug: Veliparib | Phase 1 Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 24 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | October 22, 2012 |
| Actual Primary Completion Date : | February 15, 2018 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm I (veliparib, combination chemotherapy)
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.
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Drug: Carboplatin
Given IV
Other Names:
Drug: Cisplatin Given IV
Other Names:
Drug: Fluorouracil Given IV
Other Names:
Drug: Hydroxyurea Given PO
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Paclitaxel Given IV
Other Names:
Radiation: Radiation Therapy Undergo radiation therapy
Other Names:
Drug: Veliparib Given PO
Other Names:
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Experimental: Arm II (placebo, 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.
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Drug: Carboplatin
Given IV
Other Names:
Drug: Cisplatin Given IV
Other Names:
Drug: Fluorouracil Given IV
Other Names:
Drug: Hydroxyurea Given PO
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Paclitaxel Given IV
Other Names:
Other: Placebo Administration Given PO Radiation: Radiation Therapy Undergo radiation therapy
Other Names:
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- Dose Limiting Toxicity (Phase I) [ Time Frame: Up to 3 weeks ]
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.
- Relative Change in Tumor Size as Measured by RECIST (Phase II) [ Time Frame: From baseline to 6 weeks ]Treatment arms will be compared using the nonparametric Wilcoxon rank-sum test.
- Toxicity (Phase I and Phase II) [ Time Frame: upt to 5 years ]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.
- PFS (Phase II) [ Time Frame: Up to 5 years ]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.
- Disease-free Survival (Phase II) [ Time Frame: Up to 5 years ]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.
- Time to Local or Distant Progression (Phase II) [ Time Frame: Up to 5 years ]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.
- DSS (Phase II) [ Time Frame: Up to 5 years ]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.
- OS (Phase II) [ Time Frame: Up to 5 years ]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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- PHASE I:
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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:
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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
- 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
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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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01711541
| United States, Illinois | |
| Northwestern University | |
| Chicago, Illinois, United States, 60611 | |
| University of Chicago Comprehensive Cancer Center | |
| Chicago, Illinois, United States, 60637 | |
| NorthShore University HealthSystem-Evanston Hospital | |
| Evanston, Illinois, United States, 60201 | |
| United States, Missouri | |
| Washington University School of Medicine | |
| Saint Louis, Missouri, United States, 63110 | |
| United States, North Carolina | |
| UNC Lineberger Comprehensive Cancer Center | |
| Chapel Hill, North Carolina, United States, 27599 | |
| Principal Investigator: | Jonas De Souza | Alliance for Clinical Trials in Oncology |
Documents provided by National Cancer Institute (NCI):
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT01711541 |
| Other Study ID Numbers: |
NCI-2012-02009 NCI-2012-02009 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) A091101 A091101 ( Other Identifier: Alliance for Clinical Trials in Oncology ) A091101 ( Other Identifier: CTEP ) N01CM62201 ( U.S. NIH Grant/Contract ) U10CA180821 ( U.S. NIH Grant/Contract ) U10CA031946 ( U.S. NIH Grant/Contract ) |
| First Posted: | October 22, 2012 Key Record Dates |
| Results First Posted: | June 5, 2019 |
| Last Update Posted: | January 27, 2023 |
| Last Verified: | January 2023 |
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Carcinoma Carcinoma, Squamous Cell Squamous Cell Carcinoma of Head and Neck Oropharyngeal Neoplasms Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms, Squamous Cell Head and Neck Neoplasms Neoplasms by Site Pharyngeal Neoplasms Otorhinolaryngologic Neoplasms Pharyngeal Diseases Stomatognathic Diseases Otorhinolaryngologic Diseases |
Paclitaxel Cisplatin Carboplatin Fluorouracil Albumin-Bound Paclitaxel Hydroxyurea Veliparib Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antimetabolites Antimetabolites, Antineoplastic |