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

Study Description

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Brief 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.

Condition or disease	Intervention/treatment	Phase
Large Cell Lung Carcinoma; Lung Adenocarcinoma; Lung Adenocarcinoma, Mixed Subtype; Minimally Invasive Lung Adenocarcinoma; Squamous Cell Lung Carcinoma; Stage III Non-Small Cell Lung Cancer AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7	Radiation: 3-Dimensional Conformal Radiation Therapy; Drug: Carboplatin; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Other: Placebo; Drug: Veliparib	Phase 1; Phase 2

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Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	162 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Single (Participant)
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), (NCI Study Number 8811)
Actual Study Start Date :	June 20, 2011
Estimated Primary Completion Date :	January 2, 2021
Estimated Study Completion Date :	January 2, 2021

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Arm I (RT, veliparib, carboplatin, paclitaxel); Patients undergo 3D-CRT and receive veliparib, carboplatin, and paclitaxel as in Phase I induction and consolidation therapy.	Radiation: 3-Dimensional Conformal Radiation Therapy; Undergo 3D-conformal RT; Other Names: 3-dimensional radiation therapy; 3D CONFORMAL RADIATION THERAPY; 3D CRT; 3D-CRT; Conformal Therapy; Radiation Conformal Therapy Drug: Carboplatin; Given IV; Other Names: Blastocarb; Carboplat; Carboplatin Hexal; Carboplatino; Carbosin; Carbosol; Carbotec; CBDCA; Displata; Ercar; JM-8; Nealorin; Novoplatinum; Paraplatin; Paraplatin AQ; Paraplatine; Platinwas; Ribocarbo Other: Laboratory Biomarker Analysis; Correlative studies Drug: Paclitaxel; Given IV; Other Names: Anzatax; Asotax; Bristaxol; Praxel; Taxol; Taxol Konzentrat Drug: Veliparib; Given PO; Other Names: ABT-888; PARP-1 inhibitor ABT-888
Active Comparator: Arm II (3D-CRT, placebo, carboplatin, paclitaxel); 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.	Radiation: 3-Dimensional Conformal Radiation Therapy; Undergo 3D-conformal RT; Other Names: 3-dimensional radiation therapy; 3D CONFORMAL RADIATION THERAPY; 3D CRT; 3D-CRT; Conformal Therapy; Radiation Conformal Therapy Drug: Carboplatin; Given IV; Other Names: Blastocarb; Carboplat; Carboplatin Hexal; Carboplatino; Carbosin; Carbosol; Carbotec; CBDCA; Displata; Ercar; JM-8; Nealorin; Novoplatinum; Paraplatin; Paraplatin AQ; Paraplatine; Platinwas; Ribocarbo Other: Laboratory Biomarker Analysis; Correlative studies Drug: Paclitaxel; Given IV; Other Names: Anzatax; Asotax; Bristaxol; Praxel; Taxol; Taxol Konzentrat Other: Placebo; Given PO; Other Names: placebo therapy; PLCB; sham therapy

Outcome Measures

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Primary Outcome Measures :

1. Maximum tolerated dose of veliparib when given concurrently with standard carboplatin/paclitaxel and radiotherapy, determined according to incidence of dose limiting toxicity (DLT) (Phase I) [ Time Frame: 9 weeks ]
   DLTs will be graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
2. Progression free survival of patients treated with chemoradiotherapy plus veliparib (Phase II), assessed by Response Evaluation Criteria in Solid Tumors [ Time Frame: The time from randomization to progression or death due to any cause, assessed up to 5 years ]
   A stratified log-rank test at the 10% level will be used.

Secondary Outcome Measures :

1. Objective response rate, assessed by Response Evaluation Criteria in Solid Tumors (Phase II) [ Time Frame: Up to 5 years ]
   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
2. Incidence of serious (>= grade 3) adverse events as measured by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Phase II) [ Time Frame: Up to 4 weeks after completion of consolidation therapy ]
   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.
3. Progression free survival (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 ]
   Survival data will be analyzed using Kaplan-Meier analysis. Time to progression will be displayed for all patients and for patients who have responded.
4. Overall survival (Phase II) [ Time Frame: Up to 5 years ]
   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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
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 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 using the Cockroft-Gault formula
• 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/mcl
• 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

Contacts and Locations

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Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Principal Investigator:	Athanassios (Ethan) Argiris	Southwest Oncology Group

More Information

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Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT01386385 History of Changes
Other Study ID Numbers:	NCI-2011-02592; NCI-2011-02592 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); CHNMC-PHII-111; S1206; CDR0000701003; PHII-111; 8811 ( Other Identifier: SWOG ); 8811 ( Other Identifier: CTEP ); N01CM62209 ( U.S. NIH Grant/Contract ); U10CA180888 ( U.S. NIH Grant/Contract ); U10CA032102 ( U.S. NIH Grant/Contract )
First Posted:	July 1, 2011
Last Update Posted:	April 13, 2018
Last Verified:	November 2017

Additional relevant MeSH terms:

Carcinoma; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic	Bronchial Neoplasms; Paclitaxel; Veliparib; Albumin-Bound Paclitaxel; Carboplatin; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Poly(ADP-ribose) Polymerase Inhibitors; Enzyme Inhibitors