Metformin in Non Small Cell Lung Cancer (NSCLC)

NCT02285855 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 2014-0255NCI-2015-00287
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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.

Conditions

Lung Cancer

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

Outcome Measures

Primary Outcomes (1)

• 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).

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

Study Arms (2)

Stereotactic body Radiotherapy (SBRT) + Metformin

EXPERIMENTAL

Participants randomized to Metformin treatment receive Metformin for 3 weeks prior to SBRT treatment and for 1 week during SBRT treatment. Metformin administered 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. SBRTdelivered per standard of care practice.

Drug: Metformin; Radiation: Stereotactic body Radiotherapy (SBRT)

Stereotactic Body Radiotherapy (SBRT) + Placebo

PLACEBO COMPARATOR

Participants randomized to placebo treatment 3 weeks prior to SBRT treatment and for 1 week during SBRT treatment. Placebo administered by mouth three times a day. SBRT delivered per standard of care practice.

Other: Placebo; Radiation: Stereotactic body Radiotherapy (SBRT)

Interventions

Metformin DRUG

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.

Also known as: Metformin ER

Stereotactic body Radiotherapy (SBRT) + Metformin

Placebo OTHER

Placebo treatment given 3 weeks prior to SBRT treatment and for 1 week during SBRT treatment. Placebo administered by mouth three times a day.

Also known as: Sugar pill

Stereotactic Body Radiotherapy (SBRT) + Placebo

Stereotactic body Radiotherapy (SBRT) RADIATION

SBRT delivered per standard of care practice as determined by participant's physician.

Also known as: SBRT, XRT

Stereotactic Body Radiotherapy (SBRT) + Placebo; Stereotactic body Radiotherapy (SBRT) + Metformin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with pathologic diagnosis of lung NSCLC or squamous cell carcinoma.
• Patients are to be treated with hypofractionated RT.
• Patient is not a surgical candidate due to medical comorbidities determined by a thoracic surgeon or patient refusal
• Patient plans to receive treatment at MD Anderson
• Patients must sign informed consent
• 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

You may not qualify if:

• Patient has: random glucose \>200 mg/dl or is taking an oral hypoglycemic agent or insulin at the time of study entry
• Patient has a history of lactic acidosis, chronic kidney disease or a creatinine \>/= 1.2 mg/dl
• Women who are pregnant or breast feeding, as treatment involves unforeseeable risks to the participant, embryo, fetus, or nursing infant
• Patients with history of allergic reaction to metformin

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Chun SG, Liao Z, Jeter MD, Chang JY, Lin SH, Komaki RU, Guerrero TM, Mayo RC, Korah BM, Koshy SM, Heymach JV, Koong AC, Skinner HD. Metabolic Responses to Metformin in Inoperable Early-stage Non-Small Cell Lung Cancer Treated With Stereotactic Radiotherapy: Results of a Randomized Phase II Clinical Trial. Am J Clin Oncol. 2020 Apr;43(4):231-235. doi: 10.1097/COC.0000000000000632.

  PMID: 31990759 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma of Lung

Interventions

Metformin; Sugars; Radiosurgery

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Carbohydrates; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Stephen Chun/Assistant Professor, Radiation Oncology
• Organization: UT MD Anderson Cancer Center

sgchun@mdanderson.org

713- 563-9600

Study Officials

• Stephen G. Chun, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2014
• First Posted: November 7, 2014
• Study Start: February 20, 2015
• Primary Completion: January 5, 2019
• Study Completion: January 5, 2019
• Last Updated: January 6, 2020
• Results First Posted: January 6, 2020

Record last verified: 2019-12

Locations

US (1)