Lung Cancer
Conditions
Keywords
Lung Cancer, Non small cell lung cancer, Stereotactic body radiotherapy, SBRT, XRT, Radiation therapy, Metformin, Metformin ER, Placebo, Sugar pill, Lung adenocarcinoma, Genotypes, Genetic mutations
Brief summary
The goal of this clinical research study is to learn if giving metformin in combination with radiation therapy is more effective than radiation therapy alone. In this study, participants will receive either metformin or a placebo. A placebo is not a drug. It looks like the study drug but is not designed to treat any disease or illness. It is designed to be compared with a study drug to learn if the study drug has any real effect. This is an investigational study. Metformin is FDA approved for the treatment of diabetes. Its use in this study to be given with radiation therapy to treat lung cancer is investigational. The study doctor can explain how the study drug is designed to work. Up to 70 participants will be enrolled in this study. All will take part at MD Anderson.
Interventions
DRUGMetformin
Metformin treatment given at a dose of 2000 mg by mouth in divided dose daily (500 mg am, 1000 mg noon, 500 mg pm). To reduce GI toxicity, participants start Metformin at 1000 mg daily in a divided dose (500mg am, 500 mg pm) for 1 week.
OTHERPlacebo
Placebo treatment given 3 weeks prior to SBRT treatment and for 1 week during SBRT treatment. Placebo administered by mouth three times a day.
RADIATIONStereotactic body Radiotherapy (SBRT)
SBRT delivered per standard of care practice as determined by participant's physician.
Sponsors
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with pathologic diagnosis of lung NSCLC or squamous cell carcinoma. 2. Patients are to be treated with hypofractionated RT. 3. Patient is not a surgical candidate due to medical comorbidities determined by a thoracic surgeon or patient refusal 4. Patient plans to receive treatment at MD Anderson 5. Patients must sign informed consent 6. Patient must have adequate renal function within 30 days prior to registration, defined as serum creatinine within normal institutional limits or creatinine clearance at least 60 ml/min
Exclusion criteria
1. Patient has: random glucose \>200 mg/dl or is taking an oral hypoglycemic agent or insulin at the time of study entry 2. Patient has a history of lactic acidosis, chronic kidney disease or a creatinine \>/= 1.2 mg/dl 3. Women who are pregnant or breast feeding, as treatment involves unforeseeable risks to the participant, embryo, fetus, or nursing infant 4. Patients with history of allergic reaction to metformin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| RECIST and PERCIST Tumor Response | From baseline (prior to metformin start) to Post-Radiotherapy (RT) Treatment, assessed up to 6 months | The primary objective is the effect of metformin on response in NSCLC patients treated with hypofractionated RT. All patients will receive FDG-PET/CT scan at baseline (prior to metformin start), prior to RT and at 6 months (+/- 30 days) following RT. PET/CT imaging using \[18F\]-2-fluoro-2-deoxyglucose positron emission tomography (18F-FDG), using a standard approved radiopharmaceutical dose and administration selected by the nuclear medicine physician (120 min). Response will be determined at 6 months post-treatment via relative change from pre-treatment tumor by Response Evaluation Criteria in Solid Tumor (RECIST) by complete response (CR), partial response (PR) and stable disease (SD) and PET Response Criteria in Solid Tumors (PERCIST) by stable metabolic disease (SMD), progressive metabolic disease (PMD) and complete metabolic response(CMR). |
Countries
United States
Participant flow
Recruitment details
A total of 18 lung non-small cell lung cancer (NSCLC) patients were consented and randomized. Eligible criteria: pathologic diagnosis of AJCC Stage I-II, cT1-T2N0M0, can be treated with hypofractionated radiotherapy, not a surgical candidate, have adequate renal function within 30 days prior to registration, and plans to receive treatment at MDACC.
Pre-assignment details
A total of 27 patients were consented to this study, but 9 patients withdrew consent prior to protocol medication or treatment. 18 patients randomized and treated under this protocol.
Participants by arm
| Arm | Count |
|---|---|
| Metformin Arm Patients randomized to metformin arm will receive 3 weeks of daily metformin (500 mg, am, 1000 mg, noon, 500 mg, pm) and then SBRT to a total dose of 50-70 Gy in 4-15 daily treatment fractions with metformin. | 16 |
| Placebo Arm Patients randomized to placebo treatment will receive 3 weeks of daily placebo and then SBRT to a total dose of 50-70 Gy in 4-15 daily treatment fractions with placebo. | 2 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Total | Placebo Arm | Metformin Arm |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 15 Participants | 2 Participants | 13 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 0 Participants | 3 Participants |
| Age, Continuous | 71.3 Years | 69.3 Years | 73.3 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 2 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 16 Participants | 2 Participants | 14 Participants |
| Region of Enrollment United States | 18 participants | 2 participants | 16 participants |
| Sex: Female, Male Female | 10 Participants | 1 Participants | 9 Participants |
| Sex: Female, Male Male | 8 Participants | 1 Participants | 7 Participants |
| Total 15 patients completed treatment under the protocol and evaluable for data analysis. (AJJC) Disease Stage 1A | 4 Participants | 1 Participants | 3 Participants |
| Total 15 patients completed treatment under the protocol and evaluable for data analysis. (AJJC) Disease Stage 1B | 11 Participants | 0 Participants | 11 Participants |
| Total 15 patients completed treatment under the protocol and evaluable for data analysis. (AJJC) Disease T Stage T1a | 3 Participants | 1 Participants | 2 Participants |
| Total 15 patients completed treatment under the protocol and evaluable for data analysis. (AJJC) Disease T Stage T1b | 1 Participants | 0 Participants | 1 Participants |
| Total 15 patients completed treatment under the protocol and evaluable for data analysis. (AJJC) Disease T Stage T2a | 11 Participants | 0 Participants | 11 Participants |
| Total 15 patients completed treatment under the protocol and evaluable for data analysis. Tumor Histology Adenocarcinoma | 10 Participants | 1 Participants | 9 Participants |
| Total 15 patients completed treatment under the protocol and evaluable for data analysis. Tumor Histology Poorly differentiated carcinoma | 1 Participants | 0 Participants | 1 Participants |
| Total 15 patients completed treatment under the protocol and evaluable for data analysis. Tumor Histology Squamous Cell Carcinoma | 4 Participants | 0 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 14 | 0 / 1 |
| other Total, other adverse events | 0 / 14 | 0 / 1 |
| serious Total, serious adverse events | 1 / 14 | 0 / 1 |
Outcome results
Primary
RECIST and PERCIST Tumor Response
The primary objective is the effect of metformin on response in NSCLC patients treated with hypofractionated RT. All patients will receive FDG-PET/CT scan at baseline (prior to metformin start), prior to RT and at 6 months (+/- 30 days) following RT. PET/CT imaging using \[18F\]-2-fluoro-2-deoxyglucose positron emission tomography (18F-FDG), using a standard approved radiopharmaceutical dose and administration selected by the nuclear medicine physician (120 min). Response will be determined at 6 months post-treatment via relative change from pre-treatment tumor by Response Evaluation Criteria in Solid Tumor (RECIST) by complete response (CR), partial response (PR) and stable disease (SD) and PET Response Criteria in Solid Tumors (PERCIST) by stable metabolic disease (SMD), progressive metabolic disease (PMD) and complete metabolic response(CMR).
Time frame: From baseline (prior to metformin start) to Post-Radiotherapy (RT) Treatment, assessed up to 6 months
Population: Three participants did not complete the treatment ( Metformin Arm in 2 and Placebo Arm in 1). 15 participants randomized and completed ( Placebo Arm in 1 and Metformin Arm in 14). One participant died prior post treatment 6 months evaluation.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Metformin Arm | RECIST and PERCIST Tumor Response | Mid-treatment RECIST tumor response (SD) | 14 Participants |
| Metformin Arm | RECIST and PERCIST Tumor Response | Mid-treamtment PERCIST tumor response: (PMR) | 2 Participants |
| Metformin Arm | RECIST and PERCIST Tumor Response | Post- treatment (6 mo.) PERCIST (PMD) | 1 Participants |
| Metformin Arm | RECIST and PERCIST Tumor Response | Post-treatment (6 mo.) RECIST tumor response(CR) | 7 Participants |
| Metformin Arm | RECIST and PERCIST Tumor Response | Post-treatment (6 mo.) RECIST tumor response(PR) | 3 Participants |
| Metformin Arm | RECIST and PERCIST Tumor Response | Post-treatment (6 mo.) RECIST tumor response(SD) | 3 Participants |
| Metformin Arm | RECIST and PERCIST Tumor Response | Mid-treamtment PERCIST tumor response: (SMD) | 6 Participants |
| Metformin Arm | RECIST and PERCIST Tumor Response | Mid-treamtment PERCIST tumor response: (PMD) | 6 Participants |
| Metformin Arm | RECIST and PERCIST Tumor Response | Post- treatment (6 mo.) PERCIST (CMR) | 9 Participants |
| Metformin Arm | RECIST and PERCIST Tumor Response | Post- treatment (6 mo.) PERCIST (PMR) | 3 Participants |
| Placebo Arm | RECIST and PERCIST Tumor Response | Mid-treamtment PERCIST tumor response: (PMD) | 0 Participants |
| Placebo Arm | RECIST and PERCIST Tumor Response | Mid-treatment RECIST tumor response (SD) | 1 Participants |
| Placebo Arm | RECIST and PERCIST Tumor Response | Post-treatment (6 mo.) RECIST tumor response(SD) | 0 Participants |
| Placebo Arm | RECIST and PERCIST Tumor Response | Mid-treamtment PERCIST tumor response: (PMR) | 0 Participants |
| Placebo Arm | RECIST and PERCIST Tumor Response | Post- treatment (6 mo.) PERCIST (CMR) | 1 Participants |
| Placebo Arm | RECIST and PERCIST Tumor Response | Post- treatment (6 mo.) PERCIST (PMR) | 0 Participants |
| Placebo Arm | RECIST and PERCIST Tumor Response | Mid-treamtment PERCIST tumor response: (SMD) | 1 Participants |
| Placebo Arm | RECIST and PERCIST Tumor Response | Post-treatment (6 mo.) RECIST tumor response(CR) | 1 Participants |
| Placebo Arm | RECIST and PERCIST Tumor Response | Post- treatment (6 mo.) PERCIST (PMD) | 0 Participants |
| Placebo Arm | RECIST and PERCIST Tumor Response | Post-treatment (6 mo.) RECIST tumor response(PR) | 0 Participants |