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Metformin in Non Small Cell Lung Cancer (NSCLC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02285855
Recruitment Status : Active, not recruiting
First Posted : November 7, 2014
Last Update Posted : January 3, 2018
Sponsor:
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment Phase
Lung Cancer Drug: Metformin Other: Placebo Radiation: Stereotactic body Radiotherapy (SBRT) Phase 2

Detailed Description:

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the roll of dice) to receive either metformin or a placebo. This is done because no one knows if one study group is better, the same, or worse than the other group. For every 7 participants enrolled in this study, 6 will receive metformin and 1 will receive a placebo.

Only the study staff will know if you are receiving the study drug or the placebo.

Study Drug/Placebo Administration:

You will begin taking metformin/placebo 3 weeks before you begin radiation therapy. You will take it each week during radiation therapy. You will take the drug/placebo 3 times a day (in the morning, at noon, and in the evening).

To decrease the GI side effects you will start metformin at 1000 mg daily in a divided dose (in the morning and in the evening) for 1 week.

You will keep a log for each time that you take metformin/placebo. You should bring the log with you to each study visit.

You will also receive Benadryl (diphenhydramine) and prednisone to help prevent side effects.

There will be no change to your radiation therapy. You will receive a separate consent form that describes the radiation therapy and its risks.

Study Visits:

Every week while you are taking the study drug/placebo, blood (about 2-3 teaspoons) will be drawn for routine tests.

You will have a positron emission tomography-computed tomography (PET-CT) scan before starting metformin/placebo to check the status of the disease.

Length of Study:

You may continue taking the study drug/placebo for up to a total of 2 weeks during radiation treatment. You will no longer be able to take the study drug/placebo if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Follow-Up:

Your medical records will be checked for up to 6 months after your radiation therapy.

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.


Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Tumor Mutation Status Will Predict Metabolic Response to Metformin in Non Small Cell Lung Cancer (NSCLC)
Actual Study Start Date : February 20, 2015
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : February 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Stereotactic body Radiotherapy (SBRT) + Metformin
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
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.
Other Name: Metformin ER
Radiation: Stereotactic body Radiotherapy (SBRT)
SBRT delivered per standard of care practice as determined by participant's physician.
Other Names:
  • SBRT
  • XRT
Placebo Comparator: Stereotactic Body Radiotherapy (SBRT) + Placebo
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
Placebo treatment given 3 weeks prior to SBRT treatment and for 1 week during SBRT treatment. Placebo administered by mouth three times a day.
Other Name: Sugar pill
Radiation: Stereotactic body Radiotherapy (SBRT)
SBRT delivered per standard of care practice as determined by participant's physician.
Other Names:
  • SBRT
  • XRT


Outcome Measures

Primary Outcome Measures :
  1. Tumor Response Between Metformin and Placebo Cohorts [ Time Frame: 6 months after treatment ]
    Primary objectives to compare tumor response with RECIST versus PERCIST criteria between Metformin and placebo cohorts. Participants undergo a FDG-PET/CT scan at baseline, following 3 weeks of Metformin (for those patients randomized to the Metformin arm) and at 6 months post-SBRT. Response determined at 6 months post-treatment via relative change from pre-treatment tumor SUV of [18F]-FDG-PET after 3 weeks induction Metformin or placebo to the tumor SUV at 6 months post-treatment.


Secondary Outcome Measures :
  1. Genotype Comparisons of Kras, STK11, and TP53 Mutations [ Time Frame: Weekly for 4 weeks. ]
    Mann-Whitney tests used to test for genotype effects within each of three candidate genes and between study arms (control versus metformin treated). Among cohort of patients that present disruptive TP53 mutations, test attains at least 80-96% power to detect a difference in magnitude of at least 1.5 standard deviations between cohorts of patients with activated and inactivated Kras mutations and at least 80-94% power to detect difference in magnitude of at least 1.7 standard deviations between cohorts of patients with functional and inactivated STK11 mutations.


Other Outcome Measures:
  1. Disease Control (DC) [ Time Frame: 3 weeks after Metformin Induction ]
    Objective considers predictive power of pre-treatment glucose utilization with mutation status for resultant metformin disease control (DC) using RECIST and PERCIST criteria. DC for RECIST requires complete response (CR), partial response (PR), or SD after 3 weeks induction metformin. DC for PERCIST requires reduction in tumor SUV of [18F]-FDG-PET after 3 weeks induction metformin. Accuracy of pre-treatment SUV of [18F]-FDG-PET in predicting DC evaluated using area under the receiver operator characteristic curve (AUROC) for each tumor genotype independently and combined. Inference with multivariate logistic regression used to assess effect of pre-treatment SUV of [18F]-FDG-PET in presence of genotype status. Confounders of post-radiation chemotherapy and steroid use adjusted for using linear mixed regression modeling.


Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02285855


Locations
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Heath Skinner, MD, PHD M.D. Anderson Cancer Center
More Information

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02285855     History of Changes
Other Study ID Numbers: 2014-0255
NCI-2015-00287 ( Registry Identifier: NCI CTRP )
First Posted: November 7, 2014    Key Record Dates
Last Update Posted: January 3, 2018
Last Verified: December 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
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

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs