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)

Histologically or cytologically-proven new diagnosis of unresectable Stage IIIA/IIIB (per AJCC 7th edition), NSCLC (adenocarcinoma, bronchioalveolar cell carcinoma, large cell carcinoma, squamous cell carcinoma, or mixed). Measurable or non-measurable disease documented by CT, MRI, or PET/CT. CT from 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 only evidence of disease. Non-measurable disease must be assessed within 42 days prior to registration. No brain mets. Must have pretreatment CT or MRI scan of brain within 42 days prior to reg. No prior systemic therapy (chemo or other biologic) for lung cancer. No prior chest radiation therapy for NSCLC. No previous surgical resection. May have undergone exploratory thoracotomy, mediastinscopy, excisional biopsy or similar surgery for purpose of determining the diagnosis, stage or potential resectability of newly diagnosed lung tumor. 28 days must have elapsed since thoracic surgery (excluding mediastinoscopy or other major surgeries) and patients should have recovered from all associated toxcities at time of reg. Must not be planning to undergo a major surgical procedure while on study. Must be >/= 18 years old. Must have Zubrod performance status 0-1. Must have tumor tissue available for submission. Must be offered participation in banking for future use of specimens. Must have adequate bone marrow of the following: ANC >/= 1,500/mcl; platelets >/= 100,000/mcl; hemoglobin >/= 9.0 g/dl within 28 days prior to reg. Must have adequate hepatic function: total bilirubin with IULN and SGOT or SGPT </= 2.5 X IULN must be obtained within 28 days prior to reg. Must not be pregnant or nursing. Must have serum creatinine </= the IULN and measured or calculated creatinine clearance >/= 60 cc/min and must be obtained within 28 days prior to reg. Must have pulmonary function test including FEV1 within 84 days prior to reg; FEV1 obtained pre- or post bronchodilator must be >/= 1.2 liters/second and/or >/= 50% predicted. Must not be planning to recieve other investigational agents. Must not have for than 10% weight loss in 6 months. Must not have allergic reactions to compounds of similar chemical or biologic composition to ABT-888, carboplatin, paclitaxel, or other agents used in study. No other prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which pt is in complete remission, or any other cancer from which pt has been disease free for 5 years. No uncontrolled intercurrent illness, but not limited to ongoing or active infection, symptomatic congetive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance. No currently > Grade 1 symptomatic neuropathy-sensory. No history of seizures. No known immune deficiencies. Must be able to swallow whole capsules.
FOR PRIOR TO CONSOLIDATION THERAPY: Must have completed chemoradiotherapy per protocol and at least 4 weeks no more than 6 weeks have elapsed from last day of induction therapy. Must have undergone restaging tests and determined to have no evidence of disease progression. Must have serum creatinine </= IULN AND measured or calculated creatinine clearance >/= 60 cc/min within 14 days prior to re-reg. Must have adequate bone marrow: ANC >/= 1,500 mcl; platelets >/= 100,000/ml; hemoglobin >/= 9.0 g/dl. Must be obtained within 14 days prior to re-reg. Must have adequate hepatic function as defined by total </= IULN and SGOT and SGPT </= 2.5 x IULN. Must be obtained within 14 days prior to re-reg. Must have Zubrod performance status 0-1.