Evaluation of Clinical Safety of Combining Metformin With Anticancer Chemotherapy

NCT ID: NCT01442870

Last Updated: 2017-05-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 105 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2014-11-30

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.

Conditions

Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Metformin

Metformin

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

Metformin

No metformin

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Metformin

Metformin

Intervention Type: DRUG

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.

• 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

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;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tufts Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wasif Saif, MD

Role: PRINCIPAL_INVESTIGATOR

Tufts Medical Center

Locations

Tufts Medical Center

Boston, Massachusetts, United States

Countries

United States

References

Saif MW, Rajagopal S, Caplain J, Grimm E, Serebrennikova O, Das M, Tsichlis PN, Martell R. A phase I delayed-start, randomized and pharmacodynamic study of metformin and chemotherapy in patients with solid tumors. Cancer Chemother Pharmacol. 2019 Dec;84(6):1323-1331. doi: 10.1007/s00280-019-03967-3. Epub 2019 Oct 3.

Reference Type: DERIVED

PMID: 31583436 (View on PubMed)

Other Identifiers

Metformin Anticancer + Chemo

Identifier Type: -

Identifier Source: org_study_id