Evaluation of Clinical Safety of Combining Metformin With Anticancer Chemotherapy

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Tufts Medical Center
ClinicalTrials.gov Identifier:
NCT01442870
First received: September 21, 2011
Last updated: October 4, 2013
Last verified: October 2013
  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 Intervention Phase
Cancer
Drug: Metformin
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Prospective Evaluation of Clinical Safety of Combining Metformin With Anticancer Chemotherapy

Resource links provided by NLM:


Further study details as provided by Tufts Medical Center:

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.


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.


Enrollment: 105
Study Start Date: September 2011
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Metformin
Metformin
Drug: Metformin
Metformin
No Intervention: No metformin
No metformin during primary endpoint assessment period (at least 3 weeks). Patients will subsequently be initiated on metformin.

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01442870

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

No publications provided

Responsible Party: Tufts Medical Center
ClinicalTrials.gov Identifier: NCT01442870     History of Changes
Other Study ID Numbers: Metformin Anticancer + Chemo
Study First Received: September 21, 2011
Last Updated: October 4, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 20, 2014