Temsirolimus in Combination With Metformin in Patients With Advanced Cancers

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by M.D. Anderson Cancer Center
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01529593
First received: February 6, 2012
Last updated: April 24, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Advanced Cancers
Drug: Temsirolimus
Drug: Metformin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Temsirolimus in Combination With Metformin in Patients With Advanced Cancers

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Temsirolimus and Metformin [ Time Frame: 10 weeks ] [ Designated as safety issue: Yes ]
    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:
  • Clinical Tumor Response [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    Clinical efficacy measured by objective tumor response per RECIST criteria. Clinical response defined as Complete Response (CR) or Partial Response (PR) or at least 4 months Stable Disease (SD).


Estimated Enrollment: 104
Study Start Date: March 2012
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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


  Show Detailed Description

  Eligibility

Ages Eligible for Study:   14 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  4. Patients must be at least 5 half-lives beyond treatment with metformin and currently not taking metformin
  5. Patients may be on antidiabetic treatment other than Metformin
  6. ECOG performance status </= 1
  7. 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
  8. 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
  9. Ability to understand and willingness to sign a written informed consent document.
  10. Patients must be >/= 14 years of age.
  11. 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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01529593

Contacts
Contact: Aung Naing, MD 713-563-1930

Locations
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Aung Naing, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01529593     History of Changes
Other Study ID Numbers: 2011-0923, NCI-2012-00216
Study First Received: February 6, 2012
Last Updated: April 24, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Advanced Cancers
Metastatic cancer
Tumor response
Temsirolimus
CCI-779
Torisel
Dose limiting toxicity
DLT
Maximum tolerated dose
MTD
Metformin

Additional relevant MeSH terms:
Neoplasms
Sirolimus
Everolimus
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on August 01, 2014