Metformin and Carbohydrate Restriction With Platinum Based Chemotherapy In Stage IIIB/IV Non-Squamous Non-Small Cell Lung Cancer (NS-NSCLC)

• Status: Terminated
• Trial end date: 2016-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Metformin is thought to activate AMP-activated protein kinase (AMPK), a major sensor of cellular energy levels and a key enzyme limiting cellular growth during times of cellular stress. Once activated, this enzyme restricts anabolic processes such as protein, cholesterol and fatty acid synthesis and inhibits mTOR, a protein kinase responsible for unregulated growth. MTOR is upregulated in a variety of tumors, including NSCLC providing rationale to take advantage of this pathway with metformin.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Beth Israel Medical Center
• Collaborator: St. Luke's-Roosevelt Hospital Center
• Treatments: Metformin

Criteria

Inclusion Criteria:

1. Able to provide written consent and is amenable to compliance with protocol schedules and testing

2. Patient is > 18 years of age

3. Pathologically proven (either histologic or cytologic) diagnosis of Stage IIIB or IV non-squamous non-small cell lung cancer

4. No prior, palliative chemotherapy for stage IV lung cancer Patients who have received adjuvant chemotherapy post surgery for curative intent more than 12 months prior to development of stage IV disease are allowed.

5. Measurable disease as RECIST criteria 1.1 (Response Evaluation Criteria in Solid Tumors, Version 1.1)

6. CT Scan of the chest/abdomen/pelvis or PET Scan within 30 days of study entry

7. An MRI of the brain or Head CT Scan with contrast within 30 days of study entry if clinically indicated

8. ECOG Performance Status 0-2.

9. CBC/differential obtained within 2 weeks prior to registration on study, with adequate bone marrow function defined as follows:

• Absolute neutrophil count (ANC) >1,500 cells/ul

• Platelets > 100,000 cells/ul

• Hemoglobin > 9.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb > g/dl is acceptable.)

10. Serum creatinine < 1.5 x ULN

11. Total bilirubin < 2.0 times the institutional Upper Limit of Normal (ULN)

12. AST and ALT < 3.0 x the ULN

13. Women of childbearing potential must have:

• A negative serum or urine pregnancy test (sensitivity <= 25IU HCG/L) within 14 days prior to the start of study drug administration

• Persons of reproductive potential must agree to use and utilize an adequate method of contraception throughout treatment and for at least 90 days after study drug is stopped prior to study enrollment, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy.

14. Ability to take oral medication

Exclusion Criteria:

1. The patient has a diagnosis of squamous cell carcinoma. Adenosquamous (mixed) histologies are allowed

2. The patient has a history of type I or type II diabetes

3. Weight of less than 80% of (IBW) ideal body weight

4. Creatinine clearance less than 45 l/min as calculated by the Cockcroft-Gault equation

5. Known EGFR or ALK mutation in which targeted therapy with erlotinib or crizotinib would be the standard of care. Those patients whose tissue is not tested or have insufficient material are eligible

6. The patient is currently taking or has previously taken metformin in the past 6 months

7. The patient has received previous chemotherapy for NSCLC except in instances of adjuvant therapy post surgical resection more than 12 months prior to enrollment

8. The patient has undergone major surgery within four weeks prior to randomization.

9. The patient has undergone palliative radiation (chest, brain) to tumor sites within two weeks of randomization (except palliative radiation to the bone which can be within one week

10. Uncontrolled (untreated) brain metastasis.

11. Patient who has NCI-CTCAE Version 4 Grade >= 2 diarrhea

12. That patient has clinically relevant CAD or uncontrolled CHF

13. The patient has ongoing or active infection (requiring antibiotics) that would limit the administration of chemotherapy including active TB. HIV is allowed in this study

14. The patient has a history of neurological or psychological disorder that may interfere with the compliance of the protocol

15. Women who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks after cessation of study drug, or have a positive pregnancy test at baseline, or are pregnant or breastfeeding