A Randomized Phase II Study of Metformin plus Paclitaxel/Carboplatin/Bevacizumab in Patients with Previously Untreated Advanced/Metastatic Pulmonary Adenocarcinoma
To determine the 1 year progression free survival in patients receiving metformin in addition to standard chemotherapy ( paclitaxel, carboplatin, bevacizumab) vs. standard therapy alone in patients with previously untreated advanced or metastatic pulmonary adenocarcinoma. The rate of response and overall survival, and a study for correlation of biomarkers and response will also be conducted.
Confirmed non-squamous, NSCLC stage IV or IIIB that is not suitable for combined chemotherapy and radiation. Normal blood and organ functions. Patients may not have uncontrolled hypertension, gross hemoptysis, be on therapeutic anticoagulation, or have untreated brain metastases. Urine protein 0 to Trace by dipstick/ 24 hour urine of less than 500 mg of protein. No immunotherapy, hormonal or radiation therapy within 2 weeks of study entry and must have with recovery of side effects related to that therapy. Patients may not have a serious, non-healing wound ulcer, bone fracture or major surgical procedure within 21 days starting treatment.
This is a randomized trial. All patients (ARM A and ARM B) will receive paclitaxel 200mg/m2 over 3 hours; Carboplatin AUC 6 over 30 minutes, and Bevacizumab 15 mg/kg infusion over 30-90 minutes Day 1 every 21 days. If a patient experiences a response, remains stable and has acceptable toxicity, a maximum of 6 cycles is allowed. All patients will receive Bevacizumab 15 mg/kg Day 1 every 21 days given as maintenance therapy until progression of disease or unacceptable toxicity occurs. Arm A will continue the Metformin in combination with Bevacizumab for maintenance. ARM A: Patients will receive Metformin with an initial dose of 500 mg twice a day, taken orally with meals for 7 days. Dose will increase to 1000 mg as AM dose and 500 mg as PM dose for 7 days. Metformin will then be given as 1000 mg in both AM and PM with meals. Metformin treatment will be initiated one week before beginning chemotherapy, if possible, but chemotherapy will not be delayed for metformin loading. Metformin will continue for all cycles on the trial and with Bevacizumab as maintenance therapy until progression of disease or unacceptable toxicity occurs. ARM B: Patients will receive paclitaxel 200mg/m2 over 3 hours; Carboplatin AUC 6 over 30 minutes, and Bevacizumab 15 mg/kg infusion over 30-90 minutes Day 1 every 21 days. If a patient experiences a response or stable disease Bevacizumab will continue every 21 days as maintenance
05/25/2013 04:02 AM