AzTrials
AzTrials

Advanced CancersPhase 1NCT01529593

Temsirolimus in Combination With Metformin in Patients With Advanced Cancers

A Phase 1 study testing Temsirolimus and Metformin in people with Advanced Cancers, run by M.D. Anderson Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 14 years and older
Conditions the study is for
Advanced Cancers
What is being tested?
Temsirolimus and Metformin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
1 siteUnited States
Study dates
26 Mar 2012to 14 Mar 2025
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 14 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
  • 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 weeks (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 gonadotropin-releasing hormone [GnRH] agonist), ovarian, or breast cancer are not exclusionary
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1
  • Absolute neutrophil count >= 1000/mL
  • Platelets >= 75,000/mL
Show all 12Show fewer
  • 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

Who cannot join

  • 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
Show all 9Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase I Study of Temsirolimus in Combination With Metformin in Patients With Advanced Cancers

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.

Read the detailed description

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a dose level of temsirolimus and metformin based on when you join this study. Up to 6 dose levels of temsirolimus and metformin will be tested. Up to 6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of the combination of temsirolimus and metformin is found.

Expansion Groups:

When the highest tolerable dose of the study drug combination is found, there will be one group of up to 40 endometrial carcinoma patients enrolled in a tumor-specific expansion group.

Study Drug Administration:

The first study cycle is 42 days and each cycle after that is 28 days. Before you start taking both drugs in Cycle 1, you will take metformin only for the first 2 weeks. This is called a titration period.

On Days 15, 22, 29 and 36 of Cycle 1, you will receive temsirolimus by vein over 30-60 minutes. For each cycle after that, you will receive temsirolimus by vein over 30-60 minutes on Days 1, 8, 15, and 22.

Before you receive temsirolimus, you will receive Benadryl (diphenhydramine) by vein over 30-60 minutes to help lower the risk of allergic reactions.

You will take metformin by mouth every day at about the same time each day with a meal and cup of water (about 8 ounces). You should take it at home except on the days when you have a study visit. On study visit days, you may take the metformin before you receive the temsirolimus. Depending on your dose, you may take metformin 1-3 times daily. Your study doctor will tell you how to take this drug.

If you are taking metformin before you start this study, the study doctor will let you know how often you will take the metformin and if you will skip the titration period visits described below.

You will be given a letter to take to your home doctor(s) about your study drug administration as part of your care provided outside of MD Anderson.

Study Visits:

At every study visit, you will be asked about your health, any other drugs you are taking, and if you have had any side effects.

Exams and tests will be performed before you receive the study drugs that day. Cycle 1 Day 1 tests and exams may not have to be repeated if done within 7 days.

If you are part of the expansion group, within 7 days before Day 1 of Cycle 1:

  • Blood (about 2 teaspoons) will be drawn for pharmacodynamic (PD) testing. PD testing measures how the level of study drug in your body may affect the disease.
  • If you are part of the expansion group and have a certain mutation, you will have a biopsy for PD testing. The tumor biopsy will be collected using either a fine needle aspiration or a core biopsy, depending on the location and size of the tumor. To perform a core biopsy, a sample of tissue is removed using a hollow core needle that has a cutting edge. To collect a fine needle aspirate, a small amount of tissue is withdrawn through a needle. If you have questions about your mutation status, the doctor can discuss this with you.

On Day 1 of Cycle 1 (titration period):

  • You will have a physical exam, including measurement of your weight and vital signs.
  • Your performance status will be recorded.
  • Blood (about 4 teaspoons) will be drawn for routine tests. You will be asked to not eat anything for 8 hours before your blood draw.
  • During Week 1 only, urine will be collected for routine tests.

On Day 8 of Cycle 1 (titration period), blood (about 2 teaspoons) will be drawn for routine tests.

On Day 15 and Day 29 of Cycle 1:

  • You will have a physical exam, including measurement of your weight and vital signs.
  • Your performance status will be recorded.
  • Blood (about 2 teaspoons) will be drawn for routine tests.
  • During Week 1 only, urine will be collected for routine tests.

On Day 22 and Day 36 of Cycle 1, blood (about 2 teaspoons) will be drawn for routine tests.

If you are part of the expansion group, on Day 37 of Cycle 1:

  • Blood (about 2 teaspoons) will be drawn for PD testing.
  • If you are part of the expansion group and have a certain mutation, you will have a biopsy for PD testing.

On Day 1 of Cycles 2 and beyond:

  • You will have a physical exam, including measurement of your weight and vital signs.
  • Your performance status will be recorded.
  • Blood (about 4 teaspoons) and urine will be collected for routine tests. You will be asked to not eat anything for 8 hours before your blood draw.

On Day 15 of Cycles 2 and beyond, blood (about 2 teaspoons) will be drawn for routine tests.

About every 8 weeks, you will have an x-ray, CT scan, MRI scan, and/or PET/CT scan to check the status of the disease. If the study doctor thinks it is needed, they will be performed more often.

After about 6 months (about 6 cycles) of taking the study drugs, you will have the CT scan or MRI scan every 2-4 cycles if your study doctor thinks it is needed.

Length of Study Participation:

You may continue taking the study drugs for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over when you have completed the end-of-study visit.

End-of-Study Visit:

Within 30 days after your last dose of study drugs, you will return to the clinic. The following tests and procedures will be performed:

  • You will have a physical exam, including measurement of your weight and vital signs.
  • Your performance status will be recorded.
  • Blood (about 2 teaspoons) and urine will be collected for routine tests.

If you are part of the expansion group:

  • Blood (about 2 teaspoons) will be drawn for PD testing if the disease gets worse.
  • If you are part of the expansion group and have a certain mutation, you will have a biopsy for PD testing if the disease gets worse.
Being tested
Temsirolimus, Metformin
Keywords
Advanced Cancers, Metastatic cancer, Tumor response, Dose limiting toxicity, DLT, Maximum tolerated dose, MTD, Temsirolimus, CCI-779, Torisel, Metformin
Medical subject headings
Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TemsirolimusDrug

    Also called CCI-779, Torisel

    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.

  • MetforminDrug

    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

Study groups in NCT01529593
Study groupRoleWhat they receive
Temsirolimus + MetforminExperimentalStarting 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.
Receives: Drug: Temsirolimus; Drug: Metformin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 10 weeks

Secondary outcomes (1)

  1. Clinical Tumor Response

    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).

    Measured: 10 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Feb 2012 (estimated)
  2. Study start26 Mar 2012
  3. Primary completion14 Mar 2025
  4. Study completion14 Mar 2025

Why it stopped: 75%\<Participants

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01529593
Sponsor's protocol ID
2011-0923
Other IDs
NCI-2012-00216
Status last verified
Mar 2025
First submitted
6 Feb 2012
Last updated
24 Mar 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 39787747

  • 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.

    PubMed 24668327

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Temsirolimus and Metformin in people with Advanced Cancers, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 24 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: 75%\<Participants). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) of Temsirolimus and Metformin (time frame: 10 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01529593, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in