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

This study has suspended participant recruitment.
(Temporarily stopped for assessment.)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01386385
First received: June 30, 2011
Last updated: September 16, 2014
Last verified: July 2014
  Purpose

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. 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 or by stopping them from dividing. 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.


Condition Intervention Phase
Adenocarcinoma of the Lung
Adenosquamous Cell Lung Cancer
Bronchoalveolar Cell Lung Cancer
Large Cell Lung Cancer
Squamous Cell Lung Cancer
Stage IIIA Non-small Cell Lung Cancer
Stage IIIB Non-small Cell Lung Cancer
Drug: veliparib
Other: hydrocortisone/placebo
Drug: carboplatin
Drug: paclitaxel
Radiation: 3-dimensional conformal radiation therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • MTD of veliparib when given concurrently with standard carboplatin/paclitaxel and radiotherapy, determined according to incidence of dose limiting toxicity (DLT) graded using NCI CTCAE version 4.0 (Phase I) [ Time Frame: 9 weeks ] [ Designated as safety issue: Yes ]
  • PFS of patients treated with chemoradiotherapy plus veliparib (Phase II), assessed by RECIST [ Time Frame: The time from randomization to progression or death due to any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
    A stratified log-rank test at the 10% level will be used.


Secondary Outcome Measures:
  • Objective response rate, assessed by RECIST (Phase II) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Point estimation and confidence interval estimation will be done for response rate. A stratified chi-square test will be used to compare response between the two arms

  • Incidence of serious (>= grade 3) adverse events as measured by NCI CTCAE version 4.0 (Phase II) [ Time Frame: Up to 4 weeks after completion of consolidation therapy ] [ Designated as safety issue: Yes ]
    The maximum grade of toxicity for each category of interest will be recorded for each patient and the summary results will be tabulated by category, grade and dose level. Serious (>= grade 3) toxicities will be described on a patient-by-patient basis and will include any relevant baseline data. A stratified chi-square test will be used to compare toxicity between the two arms.

  • PFS (Phase II) [ Time Frame: The duration of time from start of treatment to time of progression or death, whichever occurs first, assessed up to 5 years ] [ Designated as safety issue: No ]
    Survival data will be analyzed using Kaplan-Meier analysis. Time to progression (TTP) will be displayed for all patients and for patients who have responded.

  • Overall survival (Phase II) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Survival data will be analyzed using Kaplan-Meier analysis. A stratified log-rank test will be used to compare overall survival. Median, 2-year, 3-year, and 5-year survival will be calculated.


Estimated Enrollment: 162
Study Start Date: June 2011
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (RT, veliparib, carboplatin, paclitaxel)
Patients undergo RT and receive veliparib, carboplatin, and paclitaxel as in phase I induction and consolidation therapy.
Drug: veliparib
Given PO
Other Name: ABT-888
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Radiation: 3-dimensional conformal radiation therapy
Undergo 3D-conformal RT
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Active Comparator: Arm II (RT, placebo, carboplatin, paclitaxel)
Patients undergo RT as in arm I. Patients also receive placebo PO BID on days 1-50 and carboplatin and paclitaxel as in arm I. Within 4-6 weeks after completion of chemoradiotherapy, patients receive placebo on days 1-7 and carboplatin and paclitaxel as in arm I.
Other: hydrocortisone/placebo
Given PO
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Radiation: 3-dimensional conformal radiation therapy
Undergo 3D-conformal RT
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 major surgeries) and patients should have recovered from all associated toxicities at the time of registration; patients must not be planning to undergo a major 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 excision repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC1) and X-ray repair complementing defective repair in Chinese hamster cells 1 (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 one 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 because of possible pharmacokinetic interactions with carboplatin, paclitaxel and ABT-888 or other agents administered during the study
  • Patients must be able to swallow whole capsules
  • 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 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
  • 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)
  • Patients must have undergone restaging tests according to the study calendar and determined to have no evidence of disease progression
  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: NCT01386385

Locations
United States, Arizona
Arizona Cancer Center at University Medical Center North
Tucson, Arizona, United States, 85719
University of Arizona Health Sciences Center
Tucson, Arizona, United States, 85724
United States, California
Tower Cancer Research Foundation
Beverly Hills, California, United States, 90211-1850
City of Hope Medical Center
Duarte, California, United States, 91010
City of Hope
Duarte, California, United States, 91010
University of Southern California/Norris Cancer Center
Los Angeles, California, United States, 90033
University of California at Davis Cancer Center
Sacramento, California, United States, 95817
United States, Colorado
University of Colorado Cancer Center - Anschutz Cancer Pavilion
Aurora, Colorado, United States, 80045
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06520
United States, Illinois
Loyola University Medical Center
Maywood, Illinois, United States, 60153
Illinois CancerCare-Peoria
Peoria, Illinois, United States, 61615
Central Illinois Hematology Oncology Center
Springfield, Illinois, United States, 60702
United States, Indiana
Fort Wayne Medical Oncology and Hematology Inc-Parkview
Fort Wayne, Indiana, United States, 46845
United States, Michigan
Henry Ford Hospital
Detroit, Michigan, United States, 48202
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
San Antonio, Texas, United States, 78229
University of Texas Health Science Center
San Antonio, Texas, United States, 78229
University Hospital
San Antonio, Texas, United States, 78229
Audie L Murphy Veterans Affairs Hospital
San Antonio, Texas, United States, 78209
Sponsors and Collaborators
Investigators
Principal Investigator: Athanassios (Ethan) Argiris Southwest Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01386385     History of Changes
Other Study ID Numbers: NCI-2011-02592, NCI-2011-02592, CHNMC-PHII-111, CDR0000701003, PHII-111, S1206, 8811, U10CA032102, N01CM62209, U10CA180888
Study First Received: June 30, 2011
Last Updated: September 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Adenocarcinoma
Adenocarcinoma, Bronchiolo-Alveolar
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Carboplatin
Paclitaxel
Hydrocortisone
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on September 18, 2014