Temsirolimus in Combination With Metformin in Patients With Advanced Cancers

NCT01529593 | Terminated Phase 1 FDA Drug

• 2 other identifiers: 2011-0923NCI-2012-00216
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of temsirolimus and metformin hydrochloride in treating patients with cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced or metastatic). Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Metformin hydrochloride is a drug used to treat diabetes that may also prevent or slow the growth of cancers. Giving temsirolimus and metformin hydrochloride together may kill more tumor cells.

Conditions

Advanced Cancers

Keywords

Advanced Cancers; Metastatic cancer; Tumor response; Dose limiting toxicity; DLT; Maximum tolerated dose; MTD; Temsirolimus; CCI-779; Torisel; Metformin

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Temsirolimus and Metformin

  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.

  10 weeks

Secondary Outcomes (1)

• Clinical Tumor Response

  10 weeks

Study Arms (1)

Temsirolimus + Metformin

EXPERIMENTAL

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; Drug: Metformin

Interventions

Temsirolimus DRUG

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.

Also known as: CCI-779, Torisel

Temsirolimus + Metformin

Metformin DRUG

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

Temsirolimus + Metformin

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Patients must have evaluable or measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1
• Absolute neutrophil count \>= 1000/mL
• Platelets \>= 75,000/mL
• Creatinine \< 1.5 mg/dl in males and \< 1.4 in females
• T. Bilirubin \</= 1.5 X ULN
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and/or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2 X ULN (=\< 5 X ULN for patients with liver and/or bone metastases)
• 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
• Ability to understand and willingness to sign a written informed consent document
• Patients in the tumor-specific endometrial carcinoma expansion cohort that have known mutation must be willing to provide consent for biopsies

You may not qualify if:

• Patients who are pregnant or breastfeeding
• Uncontrolled intercurrent illness including, but not limited to, active infection requiring hospitalization
• History of hypersensitivity to temsirolimus or metformin
• History of cerebral vascular accident (CVA), myocardial infarction or unstable angina within the previous six months before starting therapy
• New York Heart Association class III or greater congestive heart failure
• Patients with major surgery within 30 days prior to entering the study
• Patients unable to swallow oral medications or with pre-existing gastrointestinal disorders that might interfere with proper absorption of oral drugs
• Patients on drugs that are strong cytochrome P450, family 3, subfamily A, polypeptide 4 (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
• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Ahmed J, Stephen B, Khawaja MR, Yang Y, Salih I, Barrientos-Toro E, Raso MG, Karp DD, Piha-Paul SA, Sood AK, Ng CS, Johnson A, Soliman PT, Meric-Bernstam F, Lu KH, Naing A. A phase I study of temsirolimus in combination with metformin in patients with advanced or recurrent endometrial cancer. Gynecol Oncol. 2025 Feb;193:73-80. doi: 10.1016/j.ygyno.2024.12.019. Epub 2025 Jan 8.

  PMID: 39787747 DERIVED

• Liu X, Lorusso P, Mita M, Piha-Paul S, Hong DS, Fu S, McQuinn L, Asatiani E, Doyle LA, Chen HX, Hess KR, Kurzrock R, Naing A. Incidence of mucositis in patients treated with temsirolimus-based regimens and correlation to treatment response. Oncologist. 2014 Apr;19(4):426-8. doi: 10.1634/theoncologist.2013-0231. Epub 2014 Mar 25.

  PMID: 24668327 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

temsirolimus; Metformin

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Aung Naing, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2012
• First Posted: February 9, 2012
• Study Start: March 26, 2012
• Primary Completion: March 14, 2025
• Study Completion: March 14, 2025
• Last Updated: March 24, 2025

Record last verified: 2025-03

Locations

US (1)