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Veliparib With or Without Radiation Therapy, Carboplatin, and Paclitaxel in Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery

Information source: National Cancer Institute (NCI)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Bronchioloalveolar Carcinoma; Large Cell Lung Carcinoma; Lung Adenocarcinoma; Squamous Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer

Intervention: 3-Dimensional Conformal Radiation Therapy (Radiation); Carboplatin (Drug); Laboratory Biomarker Analysis (Other); Paclitaxel (Drug); Placebo (Other); Veliparib (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: National Cancer Institute (NCI)

Official(s) and/or principal investigator(s):
Athanassios (Ethan) Argiris, Principal Investigator, Affiliation: Southwest Oncology Group

Summary

This phase I/II partially randomized trial studies the side effects and best dose of veliparib when given together with radiation therapy, carboplatin, and paclitaxel and to see how well it works in treating patients with stage III non-small cell lung cancer that cannot be removed by surgery. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as carboplatin and paclitaxel, 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. It is not yet known whether radiation therapy, carboplatin, and paclitaxel are more effective with or without veliparib in treating non-small cell lung cancer.

Clinical Details

Official title: A Dose Finding Study Followed by Phase II Randomized, Placebo-Controlled Study of Veliparib (ABT-888) Added to Chemoradiotherapy With Carboplatin and Paclitaxel for Unresectable Stage III Non-small Cell Lung Cancer (NSCLC)

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Primary outcome:

MTD of veliparib when given concurrently with standard carboplatin/paclitaxel and radiotherapy, determined according to incidence of dose limiting toxicity graded using NCI CTCAE version 4.0 (Phase I)

PFS of patients treated with chemoradiotherapy plus veliparib (Phase II), assessed by RECIST

Secondary outcome:

Incidence of serious (>= grade 3) adverse events as measured by NCI CTCAE version 4.0 (Phase II)

Objective response rate, assessed by RECIST (Phase II)

Overall survival (Phase II)

PFS (Phase II)

Detailed description: PRIMARY OBJECTIVES: I. To establish the maximum tolerated dose (MTD) and the recommended phase II dose of ABT-888 (veliparib) when given concurrently with standard carboplatin/paclitaxel and radiotherapy in patients with unresectable stage III non-small cell lung cancer (NSCLC). (Phase I) II. To assess whether carboplatin/paclitaxel plus ABT-888 compared with carboplatin/paclitaxel plus placebo improves progression-free survival (PFS) in patients with unresectable stage III NSCLC. (Phase II) III. To compare overall survival (OS) in patients treated with carboplatin/paclitaxel and radiotherapy plus ABT-888 to those treated with carboplatin, paclitaxel and radiotherapy plus placebo. (Phase II) IV. To assess the response rate (confirmed and unconfirmed, complete and partial responses) and disease control rate in the subset of patients with measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. (Phase II) V. To assess the safety and toxicity profile of the regimen. (Phase II) SECONDARY OBJECTIVES: I. To collect tumor tissue from pretreatment biopsies (archival samples) for biomarker studies, including poly (ADP-ribose) polymerase 1 (PARP) activity by measuring the levels of poly-ADP-ribose, gamma-H2A histone family, member X (gamma-H2AX), and messenger ribonucleic acid (mRNA) expression levels of deoxyribonucleic acid (DNA) repair enzymes such as excision repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC1)/x-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1). II. To collect blood samples for evaluation of gamma-H2AX (circulating tumor cells) and other relevant future studies. OUTLINE: This is a phase I, dose-escalation study of veliparib followed by a randomized phase II study. PHASE I: INDUCTION THERAPY: Patients undergo 3-dimensional conformal radiation therapy (3D-CRT) once daily (QD), 5 days a week, for 6 weeks. Patients also receive veliparib orally (PO) twice daily (BID) on days 1-43 and carboplatin intravenously (IV) over 30 minutes and paclitaxel IV over 1 hour on days 1, 8, 15, 22, 36, and 43 in the absence of disease progression or unacceptable toxicity. Patients without disease progression after completion of chemoradiotherapy undergo consolidation therapy. CONSOLIDATION THERAPY: Beginning within 4-6 weeks of chemotherapy and radiation therapy, patients receive veliparib PO BID on days 1-7 (course 1) and 22-28 (course 2) and carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1 and on day 22 of course 2. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. PHASE II: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients undergo 3D-CRT and receive veliparib, carboplatin, and paclitaxel as in Phase I induction and consolidation therapy. ARM II: Patients undergo 3D-CRT as in arm I. Patients also receive placebo PO BID on days 1-43 and carboplatin and paclitaxel as in Phase I. Within 4-6 weeks after completion of chemotherapy and radiation therapy, patients receive placebo on days 1-7 and carboplatin and paclitaxel as in Phase I. After completion of study treatment, patients are followed up every 4 months for 2 years and then every 6 months for up to 3 years.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Patients must have histologically or cytologically-proven new diagnosis of

unresectable stage IIIA/IIIB*, non-small cell lung cancer (adenocarcinoma, bronchioloalveolar cell carcinoma, large cell carcinoma, squamous cell carcinoma, or mixed)

- Per the American Joint Committee on Cancer (AJCC) 7th edition, pleural and

pericardial are now considered stage M1a disease; when pleural fluid is visible on the computed tomography (CT) scan or on a chest x-ray, a thoracentesis is required to confirm that the pleural fluid is cytologically negative; patients with exudative pleural effusions are excluded, regardless of cytology; patients with effusions that are minimal (i. e. not visible on chest x-ray) that are too small to safely tap are eligible; a small effusion that has positive fludeoxyglucose F 18 (FDG) uptake on positron emission tomography (PET) has to be proven to be malignant per standard of care diagnostic procedures for the patient to be excluded

- Patients must have measurable or non-measurable disease documented by CT, magnetic

resonance imaging (MRI) or PET/CT; the CT from a combined PET/CT may be used to document only non-measurable disease unless the scan is of diagnostic quality; measurable disease must be assessed by CT within 28 days prior to registration; pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease; non-measurable disease must be assessed within 42 days prior to registration; all disease must be assessed and documented on the Baseline Tumor Assessment Form

- Patients with brain metastases are ineligible; all patients must have a pretreatment

CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to registration

- Patients must not have received any prior systemic therapy (chemotherapy or other

biologic therapy) for lung cancer

- Patients must not have received prior chest radiation therapy for NSCLC

- Patients must not have had a previous surgical resection; however, patients may have

undergone exploratory thoracotomy, mediastinoscopy, excisional biopsy or similar surgery for the purpose of determining the diagnosis, stage or potential resectability of newly diagnosed lung tumor; at least 28 days must have elapsed since thoracic surgery (excluding mediastinoscopy or other minor surgeries) and patients should have recovered from all associated toxicities at the time of registration; patients must not be planning to undergo a minor surgical procedure while on this study

- Patients must have Zubrod performance status 0-1

- Patients must have tumor tissue available for submission to assess gene expression of

ERCC1 and XRCC1; patients must also be offered participation in banking for future use of specimens

- Absolute neutrophil count >= 1,500/mcl

- Platelets >= 100,000/mcl

- Hemoglobin >= 9. 0 g/dl

- Total bilirubin within institutional upper limit of normal (IULN)

- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or

serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2. 5 x IULN

- Patients must not be pregnant or nursing; women/men of reproductive potential must

have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures

- Patients must have a serum creatinine =< the IULN AND measured or calculated

creatinine clearance >= 60 cc/min

- Patients must have pulmonary function tests (PFTs) including forced expiratory volume

in 1 second (FEV1) within 84 days prior to registration; for FEV1, the best value obtained pre- or post-bronchodilator must be >= 1. 2 liters/second and/or >= 50% predicted

- Patients may not be planning to receive any other investigational agents

- Patients must not have more than 10% weight loss in the past 6 months

- Patients must not have a history of allergic reactions attributed to compounds of

similar chemical or biologic composition to ABT-888, carboplatin, paclitaxel or other agents used in study

- No other prior malignancy is allowed except for the following: adequately treated

basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years

- Patient must not have any 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

- Patients must not currently have a >= grade 1 symptomatic neuropathy-sensory

(National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 4. 0)

- Patients must not have a history of seizures

- Patients must not have any known immune deficiencies; patients with immune deficiency

are at increased risk of lethal infections when treated with marrow-suppressive therapy; therefore, known human immunodeficiency virus (HIV) positive patients receiving combination anti-retroviral therapy are excluded from the study

- Patients must be able to swallow whole capsules

- Prestudy history and physical must be obtained within 28 days prior to registration

- All patients must be informed of the investigational nature of this study and must

sign and give written informed consent in accordance with institutional and federal guidelines

- As a part of the Oncology Patient Enrollment Network (OPEN) registration process the

treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

- REGISTRATION #2 - PRIOR TO CONSOLIDATION CHEMOTHERAPY:

- REGISTRATION #2 - PRIOR TO CONSOLIDATION CHEMOTHERAPY: Patients must have completed

chemoradiotherapy per protocol and at least four weeks but no more than six weeks must have elapsed from the last day of induction therapy (the last day of radiation)

- REGISTRATION #2 - PRIOR TO CONSOLIDATION CHEMOTHERAPY: Patients must have undergone

restaging tests according to the study calendar and determined to have no evidence of disease progression

- REGISTRATION #2 - PRIOR TO CONSOLIDATION CHEMOTHERAPY: Patients must have a serum

creatinine =< (IULN) AND measured of calculated creatinine clearance >= 60 cc/min using the Cockroft-Gault formula

- REGISTRATION #2 - PRIOR TO CONSOLIDATION CHEMOTHERAPY: Absolute neutrophil count >=

1,500 mcl

- REGISTRATION #2 - PRIOR TO CONSOLIDATION CHEMOTHERAPY: Platelets >= 100,000/ml

- REGISTRATION #2 - PRIOR TO CONSOLIDATION CHEMOTHERAPY: Hemoglobin >= 9. 0 g/dl

- REGISTRATION #2 - PRIOR TO CONSOLIDATION CHEMOTHERAPY: Total bilirubin =< IULN

- REGISTRATION #2 - PRIOR TO CONSOLIDATION CHEMOTHERAPY: SGOT (AST) or SGPT (ALT) =<

2. 5 x IULN

- REGISTRATION #2 - PRIOR TO CONSOLIDATION CHEMOTHERAPY: Patients must have Zubrod

performance status 0-1

Locations and Contacts

The University of Arizona Cancer Center-North Campus, Tucson, Arizona 85719, United States; Recruiting
Linda L. Garland, Phone: 520-626-9008
Linda L. Garland, Principal Investigator

The University of Arizona Medical Center-University Campus, Tucson, Arizona 85724, United States; Recruiting
Linda L. Garland, Phone: 520-626-9008
Linda L. Garland, Principal Investigator

Tower Cancer Research Foundation, Beverly Hills, California 90211-1850, United States; Recruiting
Solomon I. Hamburg, Phone: 310-888-8680
Solomon I. Hamburg, Principal Investigator

City of Hope Comprehensive Cancer Center, Duarte, California 91010, United States; Active, not recruiting

USC / Norris Comprehensive Cancer Center, Los Angeles, California 90033, United States; Recruiting
Barbara J. Gitlitz, Phone: 323-865-0451
Barbara J. Gitlitz, Principal Investigator

University of California Davis Comprehensive Cancer Center, Sacramento, California 95817, United States; Recruiting
Megan E. Daly, Phone: 916-734-3089
Megan E. Daly, Principal Investigator

University of Colorado Cancer Center - Anschutz Cancer Pavilion, Aurora, Colorado 80045, United States; Recruiting
William T. Purcell, Phone: 720-848-0650
William T. Purcell, Principal Investigator

Yale University, New Haven, Connecticut 06520, United States; Recruiting
Roy H. Decker, Phone: 203-785-5702
Roy H. Decker, Principal Investigator

Loyola University Medical Center, Maywood, Illinois 60153, United States; Recruiting
Kathy S. Albain, Phone: 708-226-4357
Kathy S. Albain, Principal Investigator

Illinois CancerCare-Peoria, Peoria, Illinois 61615, United States; Recruiting
Sachdev P. Thomas, Phone: 309-243-1000, Email: sthomas@ohaci.com
Sachdev P. Thomas, Principal Investigator

Central Illinois Hematology Oncology Center, Springfield, Illinois 62702, United States; Recruiting
Edem S. Agamah, Phone: 217-525-2500, Email: ihdn@aol.com
Edem S. Agamah, Principal Investigator

Fort Wayne Medical Oncology and Hematology Inc-Parkview, Fort Wayne, Indiana 46845, United States; Recruiting
Krishna A. Rao, Phone: 217-545-5817
Krishna A. Rao, Principal Investigator

Henry Ford Hospital, Detroit, Michigan 48202, United States; Recruiting
Ding Wang, Phone: 313-916-1784
Ding Wang, Principal Investigator

Wayne State University/Karmanos Cancer Institute, Detroit, Michigan 48201, United States; Active, not recruiting

M D Anderson Cancer Center, Houston, Texas 77030, United States; Recruiting
Lauren A. Byers, Phone: 713-792-3245
Lauren A. Byers, Principal Investigator

Audie L Murphy Veterans Affairs Hospital, San Antonio, Texas 78209, United States; Terminated

Cancer Therapy and Research Center at The UT Health Science Center at San Antonio, San Antonio, Texas 78229, United States; Terminated

University Hospital, San Antonio, Texas 78229, United States; Terminated

University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, United States; Recruiting
Woondong Jeong, Phone: 210-450-3800
Woondong Jeong, Principal Investigator

Additional Information

Starting date: June 2011
Last updated: July 27, 2015

Page last updated: August 23, 2015

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