Evaluation of Clinical Safety of Combining Metformin With Anticancer Chemotherapy | RxWiki

Evaluation of Clinical Safety of Combining Metformin With Anticancer Chemotherapy

Overview[ - collapse ][ - ]

Purpose	Metformin is a drug that is normally used to treat people with diabetes. New research has discovered that metformin may also kill cancer stem cells. These cancer stem cells make up only a small portion of a cancer, but may be responsible for resistance to chemotherapy or for causing recurrence of the cancer. Future studies are envisioned to that test the efficacy of administering metformin with chemotherapy. The purpose of this study is to assess the safety of administering metformin in combination with chemotherapy. Since chemotherapy and cancer itself both cause adverse events by themselves, this study is designed to have a run-in stage as well as a subsequent randomization to metformin or no metformin. The primary endpoint will compare the rate of dose-limiting toxicities between these two arms. After a period of 3 weeks for the primary endpoint comparison, all patients will receive metformin.
Condition	Cancer
Intervention	Drug: Metformin
Phase	Phase 1
Sponsor	Tufts Medical Center
Responsible Party	Tufts Medical Center
ClinicalTrials.gov Identifier	NCT01442870
First Received	September 21, 2011
Last Updated	October 4, 2013
Last verified	October 2013

Tracking Information[ + expand ][ + ]

First Received Date	September 21, 2011
Last Updated Date	October 4, 2013
Start Date	September 2011
Estimated Primary Completion Date	December 2013
Current Primary Outcome Measures	Incidence of dose limiting toxicity when metformin is added to chemotherapy [Time Frame: 1 cycle (at least 3 weeks)] [Designated as safety issue: Yes]The primary endpoint of the study will be to determine whether metformin can be safely added to a chemotherapy regimen that is previously well tolerated. The rate of dose limiting toxicities will be compared.
Current Secondary Outcome Measures	Number of Participants with Adverse Events as a Measure of Safety and Tolerability [Time Frame: 1 cycle (at least 3 weeks)] [Designated as safety issue: Yes]Secondary endpoints will include assessment of AEs ≥ grade 3 and Serious Adverse Events (SAEs), assessment of safety beyond the first cycle with metformin, and an exploration of metformin-chemotherapy drug interactions.

Descriptive Information[ + expand ][ + ]

Brief Title	Evaluation of Clinical Safety of Combining Metformin With Anticancer Chemotherapy
Official Title	Prospective Evaluation of Clinical Safety of Combining Metformin With Anticancer Chemotherapy
Brief Summary	Metformin is a drug that is normally used to treat people with diabetes. New research has discovered that metformin may also kill cancer stem cells. These cancer stem cells make up only a small portion of a cancer, but may be responsible for resistance to chemotherapy or for causing recurrence of the cancer. Future studies are envisioned to that test the efficacy of administering metformin with chemotherapy. The purpose of this study is to assess the safety of administering metformin in combination with chemotherapy. Since chemotherapy and cancer itself both cause adverse events by themselves, this study is designed to have a run-in stage as well as a subsequent randomization to metformin or no metformin. The primary endpoint will compare the rate of dose-limiting toxicities between these two arms. After a period of 3 weeks for the primary endpoint comparison, all patients will receive metformin.
Detailed Description	Not Provided
Study Type	Interventional
Study Phase	Phase 1
Study Design	Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition	Cancer
Intervention	Drug: Metformin Metformin
Study Arm (s)	Experimental: Metformin Metformin No Intervention: No metformin No metformin during primary endpoint assessment period (at least 3 weeks). Patients will subsequently be initiated on metformin.

Recruitment Information[ + expand ][ + ]

Recruitment Status	Active, not recruiting
Estimated Enrollment	105
Estimated Completion Date	December 2013
Estimated Primary Completion Date	December 2013
Eligibility Criteria	Inclusion Criteria: - Histologically or cytologically documented cancer; diagnosis of hepatocellular carcinoma may be made by characteristic radiographic and/or AFP findings 33; - Intended treatment with, or currently being treated by anti-cancer chemotherapy in the adjuvant or advanced setting; - Age 18 to 79; - Adequate renal function (serum creatinine levels <1.5 mg/dL [males], <1.4 mg/dL [females]). If a subject does not meet these criteria, but does have an estimated creatinine clearance >= 60 ml/min using the Cockroft-Gault calculation, they will be allowed. The Cockroft-Gault formula is CrCl = (140-age) x weight(kg)÷(Cr x72), where CrCl = estimated creatinine clearance and Cr is plasma creatinine in mg/dL; - Adequate hepatic parameters, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 x upper limit of normal (ULN), total bilirubin ≤ 1.5 x ULN, and alkaline phosphatase levels ≤ 2.5 x ULN; - Must anticipate receiving at least 3 cycles (or treatment periods of at least 3-weeks) of chemotherapy; - Ability to understand and willingness to sign a written informed consent document. Exclusion Criteria: - Current use of metformin (within 1 week of start of chemotherapy regimen to be assessed); - Patients with type 2 diabetes are allowed, however they will be excluded if there is intent to use metformin for treatment of diabetes during the course of the study; - Undergoing chemotherapy treatment concurrent with radiation therapy; - Undergoing chemotherapy in a neoadjuvant setting prior to potentially curative surgery; - Renal disease or renal dysfunction not meeting inclusion criteria; - Significant medical conditions such as cardiovascular collapse (shock), acute myocardial infarction, septicemia, acute or chronic metabolic acidosis; - History of, or states associated with, lactic acidosis such as shock or pulmonary insufficiency, alcoholism (acute or chronic), conditions associated with hypoxemia and pancreatitis; - Severe dehydration; - Clinical or laboratory evidence of hepatic disease; - Congestive heart failure requiring pharmacologic treatment, or unstable or acute congestive heart failure; - Known hypersensitivity to metformin hydrochloride; - Pregnant or lactating women (serum pregnancy test will be performed for all women of child-bearing potential); - Psychiatric illness or social situation that would limit compliance with study requirements and/or obscure results
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Not Provided
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT01442870
Other Study ID Numbers	Metformin Anticancer + Chemo
Has Data Monitoring Committee	Yes
Information Provided By	Tufts Medical Center
Study Sponsor	Tufts Medical Center
Collaborators	Not Provided
Investigators	Principal Investigator: Wasif Saif, MD Tufts Medical Center
Verification Date	October 2013

Locations[ + expand ][ + ]