Study of GRN163L With Paclitaxel and Carboplatin in Patients With Advanced or Metastatic Non Small Cell Lung Cancer

A Phase I Study of GRN163L in Combination With Paclitaxel and Carboplatin in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer

The purpose of this study is to determine the safety and the maximum tolerated dose (MTD) of GRN163L when administered in combination with a standard paclitaxel/carboplatin regimen to patients with advanced or metastatic non-small cell lung cancer.

GRN163L is a telomerase template antagonist with in vitro and in vivo activity in a variety of tumor model systems. Telomerase is an enzyme that is active primarily in tumor cells and is crucial for the indefinite growth of tumor cells. Inhibition of telomerase may result in antineoplastic effects.

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of NSCLC
• Stage IIIb with pleural effusion, Stage IV, or recurrent disease
• Measurable or evaluable disease by RECIST criteria
• ECOG performance status 0-1
• Adequate hepatic/renal function and platelet count
• If previously treated with an anthracycline, anthracenedione, or trastuzumab, must have left ventricular ejection fraction > 50%

Exclusion Criteria:

• More than 2 prior chemotherapy regimens for metastatic disease (prior adjuvant chemotherapy is allowed)
• Tumor progression during treatment with paclitaxel (refractory to paclitaxel)
• Taxane-based regimen within 12 weeks
• Any systemic therapy for cancer within 4 weeks
• Anti-platelet therapy within 2 weeks, other than low dose aspirin prophylaxis therapy
• Therapeutic anticoagulation therapy except for low dose warfarin (eg, 1 mg by mouth per day)
• Radiation therapy within 3 weeks
• Major surgery within 4 weeks (central line placement is allowed)
• Prolongation of PT or aPTT > the ULN or fibrinogen < the LLN
• History of or active central nervous system metastatic disease
• Any other active malignancy
• Active or chronically recurrent bleeding (eg, active peptic ulcer disease)
• Clinically significant infection
• Active autoimmune disease requiring immunosuppressive therapy
• Clinically significant cardiovascular disease or condition