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

• Status: Completed
• Trial end date: 2010-08-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: London Health Sciences Centre
• Treatments: Everolimus; Metformin; Sirolimus

Criteria

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