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 (PFS) of the combination of metformin and
standard chemotherapy in patients with previously untreated advanced or metastatic pulmonary
A. To evaluate the response to therapy and overall survival of the combination of metformin
with standard chemotherapy in patients with previously untreated advanced or metastatic
B. To determine whether LKB1 gene status in tumors is a significant determinant of response
when metformin is added to the therapy C. To acquire preliminary data regarding the effects
of metformin on uptake of fluorodeoxyglucose in tumor and normal tissues.
Treatment will be administered on an outpatient basis.
Induction Therapy (Step 1, Cycles 1-4)
Metformin starting at a dose of 500 mg twice a day, orally with meals. After one week,
increase the dose of metformin to 1000 mg as the first dose of the day and 500 mg as the
second dose. After another week, increase to 1000 mg of metformin two times a day. Metformin
treatment will be initiated one week before beginning chemotherapy, if possible, but
chemotherapy will not be delayed for metformin loading.
Paclitaxel 200 mg/m2 IV over 3 hours. For Paclitaxel pre-medication information
Carboplatin AUC = 6 mg/ml IV over 15 - 30 minutes, immediately following paclitaxel infusion
Bevacizumab 15 mg/kg IV infusion over 30 - 90 minutes
Metformin will be administered continuously, beginning one week before beginning
chemotherapy, if possible, but chemotherapy will not be delayed for metformin loading. The
other three drugs (paclitaxel, carboplatin, and bevacizumab) will be administered on day 1
of each 21 day cycle.
Patients responding to this therapy will be maintained with metformin (1000 mg twice daily)
and bevacizumab (15 mg/kg IV over 30-90 minutes on day 1 of each 21-day cycle).
Duration of Therapy
In the absence of treatment delays due to adverse events, treatment may continue until one
of the following criteria applies:
1. Disease progression,
2. Intercurrent illness that prevents further administration of treatment,
3. Unacceptable adverse events(s),
4. Patient decides to withdraw from the study, or
5. General or specific changes in the patient's condition render the patient unacceptable
for further treatment in the judgment of the investigator.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the 1 year progression-free survival (PFS) of the combination of metformin and standard chemotherapy in patients with previously untreated advanced or metastatic pulmonary adenocarcinoma.
United States: Food and Drug Administration
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