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

NCT02019979 | Terminated Phase 2 Results

• 1 other identifier: METRO 090-13
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Non-small Cell Lung Cancer Stage IIIB/IV; Non-small Cell Lung Cancer Metastatic; Nonsquamous Nonsmall Cell Neoplasm of Lung

Keywords

non squamous; non small cell; lung cancer; metformin

Outcome Measures

Primary Outcomes (1)

• Progress Free Survival

  Progress Free Survival (PFS) is defined as the time from the date of the first dose of treatment to the earlier of the dates of first disease progression per RECIST 1.1 or death from any cause.

  Time after day 1 cycle 1 to first disease progression for up to 20 months

Secondary Outcomes (2)

• Overall Survival

  up to 30 months

• Number of Participants With LKBI Mutation

  6 months

Study Arms (1)

metformin /carbohydrate restricted diet

EXPERIMENTAL

metformin and carbohydrate restricted diet added to platinum based chemotherapy regimen

Drug: metformin; Behavioral: carbohydrate restricted diet

Interventions

metformin DRUG

Addition of metformin 1000 mg po bid to standard of care platinum based chemotherapy

metformin /carbohydrate restricted diet

carbohydrate restricted diet BEHAVIORAL

addition of dietary counseling and metformin 1000 mg po bid to platinum based chemotherapy

Also known as: dietary counseling

metformin /carbohydrate restricted diet

Eligibility Criteria

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

You may qualify if:

• Able to provide written consent and is amenable to compliance with protocol schedules and testing
• Patient is \> 18 years of age
• Pathologically proven (either histologic or cytologic) diagnosis of Stage IIIB or IV non-squamous non-small cell lung cancer
• 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.
• Measurable disease as RECIST criteria 1.1 (Response Evaluation Criteria in Solid Tumors, Version 1.1)
• CT Scan of the chest/abdomen/pelvis or PET Scan within 30 days of study entry
• An MRI of the brain or Head CT Scan with contrast within 30 days of study entry if clinically indicated
• ECOG Performance Status 0-2.
• 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.)
• Serum creatinine \< 1.5 x ULN
• Total bilirubin \< 2.0 times the institutional Upper Limit of Normal (ULN)
• AST and ALT \< 3.0 x the ULN

You may not qualify if:

• The patient has a diagnosis of squamous cell carcinoma. Adenosquamous (mixed) histologies are allowed
• The patient has a history of type I or type II diabetes
• Weight of less than 80% of (IBW) ideal body weight
• Creatinine clearance less than 45 l/min as calculated by the Cockcroft-Gault equation
• 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
• The patient is currently taking or has previously taken metformin in the past 6 months
• The patient has received previous chemotherapy for NSCLC except in instances of adjuvant therapy post surgical resection more than 12 months prior to enrollment
• The patient has undergone major surgery within four weeks prior to randomization.
• 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
• Uncontrolled (untreated) brain metastasis.
• Patient who has NCI-CTCAE Version 4 Grade \>= 2 diarrhea
• That patient has clinically relevant CAD or uncontrolled CHF
• 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
• The patient has a history of neurological or psychological disorder that may interfere with the compliance of the protocol
• 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

Sponsors & Collaborators

• Beth Israel Medical Center: lead
• St. Luke's-Roosevelt Hospital Center: collaborator

Study Sites (4)

Beth Israel Medical Center

New York, New York, 10003, United States

Location

Beth Israel Comprehensive Cancer Center

New York, New York, 10011, United States

Location

St.Luke's-Roosevelt Hospital Center

New York, New York, 10019, United States

Location

Mount Sinai Ichan School of Medicine

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Metformin; Diet, Carbohydrate-Restricted; Nutrition Assessment

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Epidemiologic Measurements; Public Health; Environment and Public Health

Limitations and Caveats

Early termination of study because PI left institution. Not all study visits completed leading to incomplete data.

Results Point of Contact

• Title: Dr. Anish Parikh
• Organization: Icahn School of Medicine at Mount Sinai

anish.parikh@mountsinai.org

(212) 241-4705

Study Officials

• Benjamin Levy, M.D.

  Beth Israel Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2013
• First Posted: December 24, 2013
• Study Start: December 1, 2013
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: May 4, 2018
• Results First Posted: May 4, 2018

Record last verified: 2018-03

Locations

US (4)