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

May 29, 2013 updated by: London Health Sciences Centre

A Phase I Study of Temsirolimus in Combination With Metformin in Advanced Solid Tumours

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

28

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • London, Ontario, Canada, N6A 4L6
        • London Regional Cancer Program at London Health Sciences Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed malignancy, including any of the following types:

    • Renal cell
    • Endometrial
    • Breast
    • Small cell lung carcinoma
    • Lymphoma
  • Metastatic or unresectable disease for which standard curative or palliative measures do not exist or are no longer effective
  • Measurable disease according to RECIST criteria
  • No unstable primary CNS tumors or metastases

PATIENT CHARACTERISTICS:

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

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:

Inclusion criteria:

  • 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:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Maximum tolerated dose and recommended phase II dose of metformin hydrochloride when administered with temsirolimus

Secondary Outcome Measures

Outcome Measure
Objective response
Survival
Frequency and severity of adverse events
Toxicity and safety, with particular reference to glucose and lipid deregulation
Antitumor activity, including tumor response rate and time to progression

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

London Health Sciences Centre

Investigators

  • Principal Investigator: Mary Mackenzie, MD, London Health Sciences Centre

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2008

Primary Completion (Actual)

February 1, 2010

Study Completion

August 1, 2010

Study Registration Dates

First Submitted

April 15, 2008

First Submitted That Met QC Criteria

April 15, 2008

First Posted (Estimate)

April 16, 2008

Study Record Updates

Last Update Posted (Estimate)

May 30, 2013

Last Update Submitted That Met QC Criteria

May 29, 2013

Last Verified

August 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CAN-LRCC-UWOREB13877
  • CDR0000593360 (Registry Identifier: PDQ (Physician Data Query))
  • WYETH-CAN-LRCC-UWOREB13877

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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