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Temsirolimus in Combination With Metformin in Patients With Advanced Cancers

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: NCT01529593
Recruitment Status : Active, not recruiting
First Posted : February 9, 2012
Last Update Posted : May 10, 2019
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential participant.

The goal of this clinical research study is to find the highest tolerable dose of the combination of temsirolimus and metformin that can be given to patients with advanced cancer. The safety of the drug combination will also be studied.

Temsirolimus is designed to block a protein called mTOR (a protein that is thought to cause cancer cells to grow) inside the cancer cell. This may interfere with the growth or spread of cancer cells or possibly kill them.

Metformin was designed to treat patients with diabetes. It may be able to block the protein mTOR and slow the growth of tumors.

This is an investigational study. Temsirolimus is FDA approved and commercially available for the treatment of renal cell carcinoma. Metformin is FDA approved and commercially available for the treatment of diabetes mellitus. The combination of these drugs to treat advanced cancer is investigational.

Up to 104 patients will take part in this study. All will be enrolled at MD Anderson.

Condition or disease Intervention/treatment Phase
Advanced Cancers Drug: Temsirolimus Drug: Metformin Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 87 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Temsirolimus in Combination With Metformin in Patients With Advanced Cancers
Actual Study Start Date : March 26, 2012
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Temsirolimus + Metformin
Starting dose of Temsirolimus 25 mg by vein weekly. Metformin titrated over 3 weeks at 500 mg by mouth daily. Four weeks of treatment constitute 1 cycle. Cycle one (1) however, will be 6 weeks long to allow for metformin titration.
Drug: Temsirolimus

Starting dose: 25 mg by vein weekly.

Expansion cohort: Once MTD is determined, or at maximum tolerated dose level explored (Level 5) if MTD is not reached, additional 14 patients enrolled.

Other Names:
  • CCI-779
  • Torisel

Drug: Metformin

Starting dose: 500 mg titrated over first 3 weeks.

Expansion cohort: Once MTD is determined, or at maximum tolerated dose level explored (Level 5) if MTD is not reached, additional 14 patients enrolled

Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of Temsirolimus and Metformin [ Time Frame: 10 weeks ]
    MTD defined as highest dose studied in which incidence of dose limiting toxicity (DLT) less than 33%. DLTs defined as adverse events (AEs) related to study agents which occur during first cycle of treatment. Toxicity must have possible, probable or definite attribution to study drugs.

Secondary Outcome Measures :
  1. Clinical Tumor Response [ Time Frame: 10 weeks ]
    Clinical efficacy measured by objective tumor response per RECIST (Response Evaluation Criteria In Solid Tumors) criteria. Clinical response defined as Complete Response (CR) or Partial Response (PR) or at least 4 months Stable Disease (SD).

Information from the National Library of Medicine

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Ages Eligible for Study:   14 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients with advanced or metastatic cancer that is refractory to standard therapies, who have relapsed after standard therapy, or whose cancers have no standard therapy that induces a complete response (CR) rate of at least 10% or improves survival by at least three months.
  2. Patients must have evaluable or measurable disease by RECIST criteria.
  3. Patients must be >/= 4 weeks beyond treatment of any chemotherapy, other investigational therapy, hormonal, biological, targeted agents or radiotherapy, and must have recovered to </= grade 1 or previous baseline for each toxicity. Exception: Patients may have received palliative low dose radiotherapy to the limbs 1-4 weeks before this therapy provided pelvis, sternum, scapulae, vertebrae, or skull were not included in the radiotherapy field. Patients who have received non-chemotherapeutic biological agents will need to wait at least 5 half-lives or 4 wks, whichever is shorter, from the last day of treatment. Continuation of hormone replacement therapy is permitted. Stable regimens of hormonal therapy i.e. for prostate cancer (e.g. leuprolide, a GnRH agonist), ovarian, or breast cancer are not exclusionary.
  4. ECOG performance status </= 1
  5. Abnormal organ function is permitted. However, patients must have absolute neutrophil count >/= 1000/mL; platelets >/= 75,000/mL; creatinine < 1.5 mg/dl in males and < 1.4 in females;T. Bilirubin </= 3 X upper limit of normal (ULN); AST (SGOT) and/or ALT (SGPT) </= 2 X ULN (</= 5 X ULN for patients with liver and/or bone metastases).
  6. Women of child-bearing potential MUST have a negative serum or urine pregnancy test unless prior hysterectomy or menopause (defined as 12 consecutive months without menstrual activity). Patients should not become pregnant or breastfeed while on this study. Sexually active patients must agree to use contraception prior to study entry, for the duration of study participation, and for 30 days after the last dose
  7. Ability to understand and willingness to sign a written informed consent document.
  8. Patients must be >/= 14 years of age.
  9. Patients in the tumor-specific endometrial carcinoma expansion cohort that have known mutation must be willing to provide consent for biopsies.

Exclusion Criteria:

  1. Patients who are pregnant or breastfeeding.
  2. Uncontrolled intercurrent illness including, but not limited to, active infection requiring hospitalization.
  3. History of hypersensitivity to temsirolimus or metformin.
  4. History of CVA, myocardial infarction or unstable angina within the previous six months before starting therapy
  5. New York Heart Association Class III or greater congestive heart failure.
  6. Patients with major surgery within 30 days prior to entering the study.
  7. Patients unable to swallow oral medications or with pre-existing gastrointestinal disorders that might interfere with proper absorption of oral drugs.
  8. Patients on drugs that are strong P450 CYP3A4 modifiers. These drugs should be stopped 5 half-lives prior to starting investigational agents with temsirolimus. The strong inducing or inhibiting agents should not restart until 1 week after the end of the study treatment. NOTE: We will allow replacement of steroids (with either prednisone or hydrocortisone) in patients with adrenalectomy.
  9. Patients with a history of any grade of persistent or chronic nausea or vomiting within the last 4 weeks related to prior therapy or disease process.

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): NCT01529593

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United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
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Principal Investigator: Aung Naing, MD M.D. Anderson Cancer Center

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: M.D. Anderson Cancer Center Identifier: NCT01529593     History of Changes
Other Study ID Numbers: 2011-0923
NCI-2012-00216 ( Registry Identifier: NCI CTRP )
First Posted: February 9, 2012    Key Record Dates
Last Update Posted: May 10, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by M.D. Anderson Cancer Center:
Advanced Cancers
Metastatic cancer
Tumor response
Dose limiting toxicity
Maximum tolerated dose
Additional relevant MeSH terms:
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Hypoglycemic Agents
Physiological Effects of Drugs
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents