Trial Outcomes & Findings for Metformin in Non Small Cell Lung Cancer (NSCLC) (NCT NCT02285855)

Last Updated: 2020-01-06

Results Overview

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).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

27 participants

Primary outcome timeframe

From baseline (prior to metformin start) to Post-Radiotherapy (RT) Treatment, assessed up to 6 months

Results posted on

2020-01-06

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	16	2
Overall Study Randomized	16	2
Overall Study COMPLETED	14	1
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Withdrawal by Subject	2	1

Baseline Characteristics

Metformin in Non Small Cell Lung Cancer (NSCLC)

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Metformin Arm n=14 Participants 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.	Placebo Arm n=1 Participants 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.
RECIST and PERCIST Tumor Response Mid-treatment RECIST tumor response (SD)	14 Participants	1 Participants
RECIST and PERCIST Tumor Response Post-treatment (6 mo.) RECIST tumor response(CR)	7 Participants	1 Participants
RECIST and PERCIST Tumor Response Post-treatment (6 mo.) RECIST tumor response(PR)	3 Participants	0 Participants
RECIST and PERCIST Tumor Response Post-treatment (6 mo.) RECIST tumor response(SD)	3 Participants	0 Participants
RECIST and PERCIST Tumor Response Mid-treamtment PERCIST tumor response: (SMD)	6 Participants	1 Participants
RECIST and PERCIST Tumor Response Mid-treamtment PERCIST tumor response: (PMD)	6 Participants	0 Participants
RECIST and PERCIST Tumor Response Mid-treamtment PERCIST tumor response: (PMR)	2 Participants	0 Participants
RECIST and PERCIST Tumor Response Post- treatment (6 mo.) PERCIST (CMR)	9 Participants	1 Participants
RECIST and PERCIST Tumor Response Post- treatment (6 mo.) PERCIST (PMD)	1 Participants	0 Participants
RECIST and PERCIST Tumor Response Post- treatment (6 mo.) PERCIST (PMR)	3 Participants	0 Participants

Adverse Events

Metformin Arm

Serious events: 1 serious events

Other events: 0 other events

Deaths: 1 deaths

Placebo Arm

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Metformin Arm n=14 participants at risk 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.	Placebo Arm n=1 participants at risk 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.
Gastrointestinal disorders Diarrhea	7.1% 1/14 • From the time of registration through study completion and follow up, assessed up to 6 months Adverse Events report based on Common Terminology Criteria for Adverse Events, version 4.0 (CTCAE 4.0). All in the study patient encounter or treatment areas should have access to a copy of these criteria from the start of protocol treatment. Attributable to the protocol treatment (definitely, probably, or possibly related) should be reported as well.	0.00% 0/1 • From the time of registration through study completion and follow up, assessed up to 6 months Adverse Events report based on Common Terminology Criteria for Adverse Events, version 4.0 (CTCAE 4.0). All in the study patient encounter or treatment areas should have access to a copy of these criteria from the start of protocol treatment. Attributable to the protocol treatment (definitely, probably, or possibly related) should be reported as well.

Other adverse events

Adverse event data not reported

Additional Information

Stephen Chun/Assistant Professor, Radiation Oncology

UT MD Anderson Cancer Center

Phone: 713- 563-9600

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Metformin Arm n=16 Participants 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.	Placebo Arm n=2 Participants 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.	Total n=18 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Age, Categorical >=65 years	13 Participants n=5 Participants	2 Participants n=7 Participants	15 Participants n=5 Participants
Age, Continuous	73.3 Years n=5 Participants	69.3 Years n=7 Participants	71.3 Years n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	1 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	1 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	14 Participants n=5 Participants	2 Participants n=7 Participants	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants	2 Participants n=7 Participants	16 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	16 participants n=5 Participants	2 participants n=7 Participants	18 participants n=5 Participants
Total 15 patients completed treatment under the protocol and evaluable for data analysis. (AJJC) Disease Stage 1A	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Total 15 patients completed treatment under the protocol and evaluable for data analysis. (AJJC) Disease Stage 1B	11 Participants n=5 Participants	0 Participants n=7 Participants	11 Participants n=5 Participants
Total 15 patients completed treatment under the protocol and evaluable for data analysis. (AJJC) Disease T Stage T1a	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Total 15 patients completed treatment under the protocol and evaluable for data analysis. (AJJC) Disease T Stage T1b	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Total 15 patients completed treatment under the protocol and evaluable for data analysis. (AJJC) Disease T Stage T2a	11 Participants n=5 Participants	0 Participants n=7 Participants	11 Participants n=5 Participants
Total 15 patients completed treatment under the protocol and evaluable for data analysis. Tumor Histology Adenocarcinoma	9 Participants n=5 Participants	1 Participants n=7 Participants	10 Participants n=5 Participants
Total 15 patients completed treatment under the protocol and evaluable for data analysis. Tumor Histology Squamous Cell Carcinoma	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Total 15 patients completed treatment under the protocol and evaluable for data analysis. Tumor Histology Poorly differentiated carcinoma	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants