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Evaluation of Clinical Safety of Combining Metformin With Anticancer Chemotherapy

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. Identifier: NCT01442870
Recruitment Status : Completed
First Posted : September 29, 2011
Last Update Posted : May 9, 2017
Information provided by (Responsible Party):
Tufts Medical Center

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.

Condition or disease Intervention/treatment Phase
Cancer Drug: Metformin Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 105 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Prospective Evaluation of Clinical Safety of Combining Metformin With Anticancer Chemotherapy
Study Start Date : September 2011
Actual Primary Completion Date : February 2014
Actual Study Completion Date : November 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Metformin
Drug: Metformin

No Intervention: No metformin
No metformin during primary endpoint assessment period (at least 3 weeks). Patients will subsequently be initiated on metformin.

Primary Outcome Measures :
  1. Incidence of dose limiting toxicity when metformin is added to chemotherapy [ Time Frame: 1 cycle (at least 3 weeks) ]
    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.

Secondary Outcome Measures :
  1. Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 1 cycle (at least 3 weeks) ]
    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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

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 identifier (NCT number): NCT01442870

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United States, Massachusetts
Tufts Medical Center
Boston, Massachusetts, United States, 02111
Sponsors and Collaborators
Tufts Medical Center
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Principal Investigator: Wasif Saif, MD Tufts Medical Center

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Responsible Party: Tufts Medical Center Identifier: NCT01442870     History of Changes
Other Study ID Numbers: Metformin Anticancer + Chemo
First Posted: September 29, 2011    Key Record Dates
Last Update Posted: May 9, 2017
Last Verified: May 2017

Additional relevant MeSH terms:
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Hypoglycemic Agents
Physiological Effects of Drugs