Metformin and Temsirolimus in Treating Patients With Metastatic or Unresectable Solid Tumor or Lymphoma

NCT ID: NCT00659568

Last Updated: 2013-05-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-03-31
• Study Completion Date: 2010-08-31

Brief Summary

RATIONALE: Metformin and temsirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of metformin when given together with temsirolimus in treating patients with metastatic or unresectable solid tumor or lymphoma.

Detailed Description

OBJECTIVES:

Primary

• To establish the maximum tolerated dose and recommended phase II dose of metformin hydrochloride when administered with temsirolimus in patients with advanced solid cancers or lymphoma.

Secondary

• To determine the toxicity and safety, with particular reference to glucose and lipid deregulation, of this regimen in these patients.
• To assess antitumor activity, including tumor response rate and time to progression, in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of metformin hydrochloride.

Patients receive oral metformin once, twice, or three times daily on days 1-28 and temsirolimus IV over 30-60 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

Conditions

Breast Cancer; Endometrial Cancer; Kidney Cancer; Lung Cancer; Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NON_RANDOMIZED
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

metformin hydrochloride

Intervention Type: DRUG

temsirolimus

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%
• Life expectancy > 12 weeks
• Absolute neutrophil count ≥ 1.5 x 10^9/L
• Platelets ≥ 100 x 10^9/L
• AST ≤ 2.5 times upper limit of normal (ULN)
• Serum creatinine ≤ ULN
• Serum bilirubin ≤ 1.5 times ULN
• Negative pregnancy test
• Fertile patients must use effective contraception
• Able to understand and willing to sign a written informed consent document

• Recovered from all prior therapy
• At least 4 weeks since prior chemotherapy or radiotherapy (6 weeks for carmustine or mitomycin C) except low-dose, non-myelosuppressive radiotherapy
• No limitation on other prior therapy
• Concurrent low-dose anticoagulant (i.e., warfarin) allowed provided INR ≤ 1.1 times ULN
• Concurrent full-dose anticoagulant (i.e., warfarin) allowed provided INR is within institutional therapeutic range (usually 2.0-3.0)

Exclusion Criteria

• Allergies to or a history of allergic reactions attributed to any other compound of similar chemical or biologic composition to temsirolimus or metformin
• Diabetes mellitus (type I or II)
• Uncontrolled hypertriglyceridemia (triglyceride levels > 10 mmol/L)
• History of lactic acidosis
• Inability to swallow or digest oral medications
• Uncontrolled intercurrent illness including, but not limited to, any of the following:

• Uncontrolled hypertension
• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Psychiatric illness/social situation that would limit compliance with study requirements
• Significant traumatic injury within 21 days prior to treatment

PRIOR CONCURRENT THERAPY:

• Major surgery within the past 21 days
• Prior temsirolimus (or other known inhibitors of mammalian target of rapamycin) or metformin
• Concurrent combination antiretroviral therapy for HIV-positive patients
• Concurrent enzyme-inducing anti-epileptic drugs (EIAEDs) (e.g., phenytoin, carbamazepine, or phenobarbital) or other CYP3A4 inducer (e.g., rifampin or Hypericum perforatum [St. John's wort])
• Concurrent investigational or commercial agents or therapies to treat the patient's malignancy
• Other concurrent investigational agents other than temsirolimus or metformin

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

Sponsors

London Health Sciences Centre

OTHER

Sponsor Role: lead

Principal Investigators

Mary Mackenzie, MD

Role: PRINCIPAL_INVESTIGATOR

London Health Sciences Centre

Locations

London Regional Cancer Program at London Health Sciences Centre

London, Ontario, Canada

Countries

Canada

Other Identifiers

CDR0000593360

Identifier Type: REGISTRY

Identifier Source: secondary_id

WYETH-CAN-LRCC-UWOREB13877

Identifier Type: -

Identifier Source: secondary_id

CAN-LRCC-UWOREB13877

Identifier Type: -

Identifier Source: org_study_id