Randomized Phase 3 Trial of Gemcitabine/Carboplatin With or Without Iniparib (SAR240550) (a PARP1 Inhibitor) in Subjects with Previously Untreated Stage IV Squamous Non Small Cell Lung Cancer (NSCLC)

1. Newly diagnosed, stage IV squamous NSCLC. This includes patients who present
with disseminated metastases, and those with a malignant pleural or pericardial
effusion (i.e., formerly stage IIIB in the 6th TNM staging system).
2. Patients who have received prior adjuvant therapy for early-stage lung cancer are
eligible if at least 12 months have elapsed from that treatment.
3. Histologically confirmed squamous cell bronchogenic carcinoma. Patients whose
tumors have mixed non-small cell histologies are eligible, as long as squamous
carcinoma is the predominant histology. Mixed tumors with small cell anaplastic
elements are not eligible. Cytologic specimens obtained by brushings, washings, or
needle aspiration of the defined lesion are acceptable.
4. Patients with previous thoracic radiotherapy as definitive therapy for locally advanced nonsmall
cell lung cancer are eligible, as long as the recurrence is outside the original
radiation therapy port. Radiation therapy must have been completed >4 weeks prior
to the initiation of study treatment.
5. Presence of evaluable (measureable or non-measureable) disease.
6. ECOG Performance Status of 0 or 1 (see Appendix A).
7. Laboratory values as follows:
· Absolute neutrophil count (ANC) >=1,500/mL and platelet count >=100,000/mL
(<=72 hours prior to initial treatment)
· Hemoglobin >9 g/dL (Note: patients may be transfused or receive erythropoietin
to maintain or exceed this level).
· Bilirubin < ULN.
· Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=2.5 times
the upper limit of normal if no liver involvement or <=5 times the upper limit of
normal with liver involvement.
· Creatinine <=2.0 mg/dL, or creatinine clearance >=40 mL/min (as calculated by the
Cockcroft-Gault method (see Section 8.3.3). Calculated creatinine
clearance will be used to calculate carboplatin dose.
8. Women of childbearing potential must have a negative serum pregnancy test
performed within 7 days prior to start of treatment. Women of childbearing potential
or men with partners of childbearing potential must use effective birth control
measures during treatment, and at least 6 months after the last dose of study
treatment. If a woman becomes pregnant or suspects she is pregnant while
participating in this study, she must agree to inform her treating physician
immediately. Sexually active men must agree to
use a medically acceptable form of birth control during treatment and at least 6 months
after the last dose. If a female partner becomes pregnant during the course of study the
treating physician should be informed immediately.
9. 18 years of age or older.
10. Ability to understand the nature of this study, give written informed consent, and
comply with study requirements.
11. Patients entering this study must be willing to provide tissue from a previous tumor
biopsy (if available) for correlative testing. If tissue is not available/accessible, a patient will
still be eligible for enrollment into the study.

1. Prior treatment with gemcitabine, carboplatin (except in the adjuvant setting), or
BSI-201.
2. Past or current history of neoplasm other than the entry diagnosis, with the exception
of t1) reated non-melanoma skin cancer, 2) treated non-invasive or in-situ carcinoma of any primary site or 3) invasive cancers treated definitively, with treatment ending >5 years previously and no evidence of recurrence.
3. A history of active cardiac disease, within the previous 6 months, including any of the following:
· Malignant hypertension;
· Unstable angina;
· Congestive heart failure;
· Myocardial infarction within the previous 6 months;
· Symptomatic unstable or uncontrolled cardiac arrhythmias.
4. Active brain metastases. Patients with treated brain metastases are eligible if
(1) radiation therapy was completed at least 2 weeks prior to study treatment; (2) followup
scan shows no disease progression; (3) patient does not require steroids.
5. Women who are pregnant or lactating.
6. Any serious, active infection (> grade 2) at the time of treatment.
7. A serious underlying medical condition that would impair the ability of the patient to
receive protocol treatment.
8. A major surgical procedure, or significant traumatic injury -28 days of
beginning treatment, or anticipation of the need for major surgery during the course
of the study.
9. Uncontrolled or intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac
arrhythmia.
10. History of any medical or psychiatric condition or laboratory abnormality that, in the
opinion of the investigator, may increase the risks associated with the study
participation or administration of the investigational products, or that may interfere
with the interpretation of the results.
11. Known or suspected allergy/hypersensitivity to any agent given in the course of this
trial.
12. Use of any non-approved or investigational agent <=30 days prior to
administration of the first dose of study drug. Patients may not receive any
other investigational or anti-cancer treatments while participating in this study