Randomized Phase II Trial of Concurrent Chemoradiotherapy +/- Metformin HCL in Locally Advanced NSCLC
Overview
- Phase
- Phase 2
- Intervention
- Radiation Therapy
- Conditions
- Adenosquamous Lung Carcinoma
- Sponsor
- NRG Oncology
- Enrollment
- 170
- Locations
- 222
- Primary Endpoint
- Percentage of Participants Alive Without Progression (Progression-free Survival)
- Status
- Completed
- Last Updated
- 6 months ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
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:
- •History/physical examination, including documentation of height, weight, body surface area, and vital signs, within 30 days prior to registration
- •Computed tomography (CT) with IV contrast or magnetic resonance imaging (MRI) imaging (if CT scan with contrast is medically contraindicated) of the lung and upper abdomen through the adrenal glands, required within 45 days prior to registration (recommended within 30 days prior to registration
- •MRI of the brain with contrast (or CT with contrast if MRI is medically contraindicated) within 45 days prior to registration; note: the use of intravenous contrast is required for the MRI or CT; an MRI without contrast is only permitted if the patient has a contrast allergy
- •Whole-body fludeoxyglucose (FDG)-positron emission tomography (PET)/CT required within 45 days prior to registration (recommended within 30 days prior to registration; note: patients do not need to have a separate CT of the chest and upper abdomen with contrast if PET/CT imaging includes a high quality CT with contrast
- •Zubrod performance status 0-1
- •Absolute neutrophil count (ANC) \>= 1,500 cells/mm\^3
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:
Arms & Interventions
Chemoradiation
60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin
Intervention: Radiation Therapy
Chemoradiation
60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin
Intervention: Carboplatin
Chemoradiation
60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin
Intervention: Paclitaxel
Metformin + Chemoradiation
Metformin plus 60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin
Intervention: Radiation Therapy
Metformin + Chemoradiation
Metformin plus 60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin
Intervention: Carboplatin
Metformin + Chemoradiation
Metformin plus 60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin
Intervention: Metformin
Metformin + Chemoradiation
Metformin plus 60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin
Intervention: Paclitaxel
Outcomes
Primary Outcomes
Percentage of Participants Alive Without Progression (Progression-free Survival)
Time Frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.
Progression is defined per RECIST v1.1 as change in a known lesion(s) meeting one of the following criteria: \[1\] At least a 20% increase in the sum of the longest diameter of target lesions such that the absolute increase must be \> 5 mm. \[2\] Appearance of ≥1 new lesions. Progression-free survival time is defined as time from randomization to the date of first progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 progression-free survival events were reported.
Secondary Outcomes
- Percentage of Participants With Distant Metastases(From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.)
- Percentage of Participants With Treatment-related Grade 3 or Higher Adverse Events(From start of treatment to last follow-up. Maximum follow-up at time of analysis was 47.2 months.)
- Percentage of Participants Alive (Overall Survival)(From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.)
- Percentage of Participants With Local-regional Progression(From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.)