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

Primary Purpose

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

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Carboplatin

Cisplatin

Fluorouracil

Hydroxyurea

Laboratory Biomarker Analysis

Paclitaxel

Placebo Administration

Radiation Therapy

Veliparib

About this trial

This is an interventional treatment trial for Head and Neck Squamous Cell Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 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
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

Sites / Locations

Northwestern University
University of Chicago Comprehensive Cancer Center
NorthShore University HealthSystem-Evanston Hospital
Washington University School of Medicine
UNC Lineberger Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Arm I (veliparib, combination chemotherapy)

Arm II (placebo, combination chemotherapy)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

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

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

Secondary Outcome Measures

Toxicity (Phase I and Phase II)

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)

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 to Local or Distant Progression (Phase II)

DSS (Phase II)

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)

Full Information

NCT ID

NCT01711541

First Posted

October 18, 2012

Last Updated

June 6, 2023

Sponsor

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT01711541

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Completed

Study Start Date

October 22, 2012 (Actual)

Primary Completion Date

February 15, 2018 (Actual)

Study Completion Date

May 15, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

5. Study Description

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.

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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm I (veliparib, combination chemotherapy)

Arm Type

Experimental

Arm Description

Arm Title

Arm II (placebo, combination chemotherapy)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Carboplatin

Other Intervention Name(s)

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

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Other Intervention Name(s)

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

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Fluorouracil

Other Intervention Name(s)

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

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Hydroxyurea

Other Intervention Name(s)

Droxia, Hydrea, Hydroxycarbamide, Litalir, Onco-Carbide, Oncocarbide, Oxeron, SQ 1089, SQ-1089, Syrea, WR 83799

Intervention Description

Given PO

Intervention Type

Other

Intervention Name(s)

Laboratory Biomarker Analysis

Intervention Description

Correlative studies

Intervention Type

Drug

Intervention Name(s)

Paclitaxel

Other Intervention Name(s)

Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Intervention Description

Given IV

Intervention Type

Other

Intervention Name(s)

Placebo Administration

Intervention Description

Given PO

Intervention Type

Radiation

Intervention Name(s)

Radiation Therapy

Other Intervention Name(s)

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

Intervention Description

Undergo radiation therapy

Intervention Type

Drug

Intervention Name(s)

Veliparib

Other Intervention Name(s)

ABT-888, PARP-1 inhibitor ABT-888

Intervention Description

Given PO

Primary Outcome Measure Information:

Title

Dose Limiting Toxicity (Phase I)

Description

Time Frame

Up to 3 weeks

Title

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

Description

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

Time Frame

From baseline to 6 weeks

Secondary Outcome Measure Information:

Title

Toxicity (Phase I and Phase II)

Description

Time Frame

upt to 5 years

Title

PFS (Phase II)

Description

Time Frame

Up to 5 years

Title

Disease-free Survival (Phase II)

Description

Time Frame

Up to 5 years

Title

Time to Local or Distant Progression (Phase II)

Description

Time Frame

Up to 5 years

Title

DSS (Phase II)

Description

Time Frame

Up to 5 years

Title

OS (Phase II)

Description

Time Frame

Up to 5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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 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 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jonas De Souza

Organizational Affiliation

Alliance for Clinical Trials in Oncology

Official's Role

Principal Investigator

Facility Information:

Facility Name

Northwestern University

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

Facility Name

University of Chicago Comprehensive Cancer Center

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60637

Country

United States

Facility Name

NorthShore University HealthSystem-Evanston Hospital

City

Evanston

State/Province

Illinois

ZIP/Postal Code

60201

Country

United States

Facility Name

Washington University School of Medicine

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Facility Name

UNC Lineberger Comprehensive Cancer Center

City

Chapel Hill

State/Province

North Carolina

ZIP/Postal Code

27599

Country

United States

12. IPD Sharing Statement

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

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