Overview
Metformin and Carbohydrate Restriction With Platinum Based Chemotherapy In Stage IIIB/IV Non-Squamous Non-Small Cell Lung Cancer (NS-NSCLC)
Status:
Terminated
Terminated
Trial end date:
2016-12-01
2016-12-01
Target enrollment:
0
0
Participant gender:
All
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 2Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
Beth Israel Medical CenterCollaborator:
St. Luke's-Roosevelt Hospital CenterTreatments:
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