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: July 22, 2014
Last verified: July 2014

June 30, 2011
July 22, 2014
June 2011
December 2016   (final data collection date for primary outcome measure)
  • 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.
  • DLT and MTD of veliparib when given concurrently with standard carboplatin/paclitaxel and radiotherapy (Phase I) [ Designated as safety issue: Yes ]
  • PFS of patients treated with chemoradiotherapy plus veliparib (Phase II) [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01386385 on ClinicalTrials.gov Archive Site
  • 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.
  • Objective response rate [ Designated as safety issue: No ]
  • Toxicities as measured by NCI CTCAE v. 4.0 [ Designated as safety issue: Yes ]
  • Time to progression and PFS [ Designated as safety issue: No ]
  • Overall survival (median, 2-year, 3-year, 5-year) [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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
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)

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.

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 (y-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 y-H2AX (circulating tumor cells) and other relevant future studies.

OUTLINE: This is a multicenter, dose-escalation study of veliparib followed by a randomized phase II study.

PHASE I:

INDUCTION THERAPY: Patients undergo 3D-conformal radiotherapy (RT) once daily, 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, 20, 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 chemoradiotherapy, patients receive veliparib PO BID on days 1-7 and carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients are stratified according to Eastern Cooperative Oncology Group (ECOG) performance status (0 vs 1), weight-loss in previous 3 months (=< 5% vs > 5%), and age (=< 65 vs > 65). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients undergo RT and receive veliparib, carboplatin, and paclitaxel as in phase I induction and consolidation therapy.

ARM II: Patients undergo RT as in arm I. Patients also receive placebo PO BID on days 1-43 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.

After completion of study therapy, patients are followed up every 4 months for 2 years and then every 6 months for 3 years.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
    Given PO
    Other Name: ABT-888
  • 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
  • Experimental: Arm I (RT, veliparib, carboplatin, paclitaxel)
    Patients undergo RT and receive veliparib, carboplatin, and paclitaxel as in phase I induction and consolidation therapy.
    Interventions:
    • Drug: veliparib
    • Drug: carboplatin
    • Drug: paclitaxel
    • Radiation: 3-dimensional conformal radiation therapy
  • 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.
    Interventions:
    • Other: hydrocortisone/placebo
    • Drug: carboplatin
    • Drug: paclitaxel
    • Radiation: 3-dimensional conformal radiation therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Suspended
162
Not Provided
December 2016   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01386385
NCI-2011-02592, NCI-2011-02592, CHNMC-PHII-111, CDR0000701003, PHII-111, S1206, 8811, U10CA032102, N01CM62209, U10CA180888
Yes
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Athanassios (Ethan) Argiris Southwest Oncology Group
National Cancer Institute (NCI)
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP