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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00659568
• Other study ID #: CAN-LRCC-UWOREB13877
• Secondary ID: CDR0000593360WYE
• Status: Completed
• Phase: Phase 1
• First received: April 15, 2008
• Last updated: May 29, 2013
• Start date: March 2008
• Est. completion date: August 2010

Study information

• Verified date: August 2010
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: August 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• metformin hydrochloride

• temsirolimus

Locations

Country	Name	City	State
Canada	London Regional Cancer Program at London Health Sciences Centre	London	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
London Health Sciences Centre

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose and recommended phase II dose of metformin hydrochloride when administered with temsirolimus			Yes
Secondary	Toxicity and safety, with particular reference to glucose and lipid deregulation			Yes
Secondary	Antitumor activity, including tumor response rate and time to progression			No
Secondary	Objective response			No
Secondary	Survival			No
Secondary	Frequency and severity of adverse events			Yes