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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)

Phase 1/Phase 2
18 Years
Open (Enrolling)
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

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Trial Information

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)


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)


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.


INDUCTION THERAPY: Patients undergo 3D-conformal radiotherapy (RT) once daily, 5 days a
week, for 7 weeks. Patients also receive veliparib orally (PO) twice daily (BID) on days
1-50 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 1-50
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.

Blood and archived tumor tissue samples are collected for biomarker studies. Bronchoscopic
tissue samples may also be collected.

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

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

- 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

- 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

- Patients must not be pregnant or nursing because of increased risk of harm to a
nursing infant or fetus including fetal death from the chemotherapeutic and biologic
agents; 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%

- 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

- 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


- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

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)

Outcome Time Frame:

9 weeks

Safety Issue:


Principal Investigator

Athanassios Argiris

Investigator Role:

Principal Investigator

Investigator Affiliation:

Southwest Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

June 2011

Completion Date:

Related Keywords:

  • 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
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Adenocarcinoma, Bronchiolo-Alveolar
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811
Central Illinois Hematology Oncology CenterSpringfield, Illinois  62701
City of Hope Medical CenterDuarte, California  91010
City of HopeDuarte, California  91010
Tower Cancer Research FoundationBeverly Hills, California  90211
Wayne State UniversityDetroit, Michigan  48202
UC Davis Comprehensive Cancer CenterSacramento, California  95817
Illinois CancerCare-PeoriaPeoria, Illinois  61615
Fort Wayne Medical Oncology and Hematology Inc - State BoulevardFort Wayne, Indiana  46845
Cancer Therapy and Research Center at The UT Health Science Center at San AntonioSan Antonio, Texas  78229
Audie L Murphy Veterans Affairs HospitalSan Antonio, Texas  78209
University HospitalSan Antonio, Texas  78229