Randomized Phase II Trial of Concurrent Chemoradiotherapy +/- Metformin HCL in Locally Advanced NSCLC
Randomized Phase II Trial of Concurrent Chemoradiotherapy +/- Metformin HCL in Locally Advanced NSCLC
This randomized phase II trial studies how well chemotherapy and radiation therapy given with or without metformin hydrochloride works in treating patients with stage III non-small cell lung cancer. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Metformin hydrochloride may shrink tumors and keep them from coming back. It is not yet known whether chemotherapy and radiation therapy is more effective when given with or without metformin hydrochloride in treating stage III non-small cell lung cancer.
PRIMARY OBJECTIVES:
I. To determine whether metformin hydrochloride (MET) added to chemoradiotherapy can improve progression-free survival (PFS) in patients with locally advanced non-small cell lung cancer (NSCLC).
SECONDARY OBJECTIVES:
I. Determine the effects of MET on overall survival (OS), time to local-regional progression (LRP), and time to distant metastasis (DM).
II. Evaluate the effect of MET on chemoradiotherapy toxicity (Common Terminology Criteria for Adverse Events, version 4 [CTCAE, v. 4]) within 1 year of completion of all treatment.
III. Collect biospecimens to develop biomarkers of MET activity.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
After completion of study treatment, patients are followed up at 4-6 weeks, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
Inclusion Criteria:
Pathologically (histologically or cytologically) proven diagnosis of stage IIIA or IIIB non-small cell lung cancer within 84 days of registration; eligible histologies include adenocarcinoma, adenosquamous, large cell carcinoma, squamous carcinoma, non-lobar and non-diffuse bronchoalveolar cell carcinoma or non-small cell lung cancer not otherwise specified)
Patients must have measurable disease
Patients must have unresectable disease, be medically inoperable, or unwilling to undergo surgical management
Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup:
Zubrod performance status 0-1
Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
Complete blood count(CBC)/differential obtained within 14 days prior to registration on study, with adequate bone marrow function defined as follows:
Adequate renal function within 14 days prior to registration, defined as serum creatinine within normal institutional limits or creatinine clearance must be at least 60 ml/min;
Adequate hepatic function within 14 days prior to registration, defined as total bilirubin ≤ 1.5 x upper limit of normal (ULN) for the institution and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase ≤ 2.5 x ULN for the institution;
Fasting blood glucose ≤ 125 mg/dL within 14 days prior to registration;
Serum albumin > 3.0 g/dl within 14 days prior to registration;
For women of childbearing potential, a serum pregnancy test within 72 hours prior to registration;
Patients with post-obstructive pneumonia are eligible provided they no longer require intravenous antibiotics at registration;
Patients must be at least 3 weeks from prior thoracotomy (if performed);
If a pleural effusion is present, the following criteria must be met at registration to exclude malignant involvement (incurable M1a disease):
Women of childbearing potential and male participants must practice adequate contraception throughout the study;
Exclusion Criteria:
Patients with mixed small cell and non-small cell histologies
Patients with distant metastasis
Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
Patients currently using metformin (metformin hydrochloride), other oral hypoglycemic agents or insulin
Patients with any history of allergic reaction to paclitaxel or other taxanes or carboplatin
Patients with a history of chronic kidney disease or lactic acidosis
Patients with >= 10% weight loss within the past month
Severe, active co-morbidity, defined as follows:
Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
Cameron Park, California 95682, United States
Roseville, California 95661, United States
Grand Rapids, Michigan 49503, United States
Saint Joseph, Michigan 49085, United States
Lebanon, New Hampshire 03756, United States
Berlin Corners, Vermont 05602, United States
Silverdale, Washington 98383, United States
Summit, Wisconsin 53066, United States