Working… Menu

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

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: NCT00659568
Recruitment Status : Completed
First Posted : April 16, 2008
Last Update Posted : May 30, 2013
Information provided by:
National Cancer Institute (NCI)

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Endometrial Cancer Kidney Cancer Lung Cancer Lymphoma Unspecified Adult Solid Tumor, Protocol Specific Drug: metformin hydrochloride Drug: temsirolimus Phase 1

Detailed Description:



  • 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.


  • 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Allocation: Non-Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of Temsirolimus in Combination With Metformin in Advanced Solid Tumours
Study Start Date : March 2008
Actual Primary Completion Date : February 2010
Study Completion Date : August 2010

Primary Outcome Measures :
  1. Maximum tolerated dose and recommended phase II dose of metformin hydrochloride when administered with temsirolimus

Secondary Outcome Measures :
  1. Toxicity and safety, with particular reference to glucose and lipid deregulation
  2. Antitumor activity, including tumor response rate and time to progression
  3. Objective response
  4. Survival
  5. Frequency and severity of adverse events

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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


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


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

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): NCT00659568

Layout table for location information
Canada, Ontario
London Regional Cancer Program at London Health Sciences Centre
London, Ontario, Canada, N6A 4L6
Sponsors and Collaborators
London Health Sciences Centre
Layout table for investigator information
Principal Investigator: Mary Mackenzie, MD London Health Sciences Centre

Layout table for additonal information Identifier: NCT00659568     History of Changes
Other Study ID Numbers: CAN-LRCC-UWOREB13877
CDR0000593360 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: April 16, 2008    Key Record Dates
Last Update Posted: May 30, 2013
Last Verified: August 2010
Keywords provided by National Cancer Institute (NCI):
unspecified adult solid tumor, protocol specific
stage III renal cell cancer
stage IV renal cell cancer
recurrent renal cell cancer
recurrent endometrial carcinoma
stage III endometrial carcinoma
stage IV endometrial carcinoma
recurrent breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer
recurrent small cell lung cancer
extensive stage small cell lung cancer
stage III adult Burkitt lymphoma
stage III adult diffuse large cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult Hodgkin lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III adult T-cell leukemia/lymphoma
stage III cutaneous T-cell non-Hodgkin lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III mantle cell lymphoma
stage III marginal zone lymphoma
stage III small lymphocytic lymphoma
stage IV adult Burkitt lymphoma
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Lung Neoplasms
Endometrial Neoplasms
Kidney Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Site
Breast Diseases
Skin Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Uterine Diseases
Genital Diseases, Female
Urologic Neoplasms
Kidney Diseases
Urologic Diseases
Hypoglycemic Agents