Temsirolimus + Metformin for Advanced Cancer

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: CYP3A4 modifiers

Disqualifiers: Pregnancy, Infection, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 8

Duration: 6 weeks for Cycle 1, 4 weeks for subsequent cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two drugs, temsirolimus and metformin, to determine the best dose and assess their combined effect on advanced cancer that has spread and resists standard treatments. Temsirolimus may inhibit cancer cell growth, while metformin, a common diabetes medication, could slow or prevent cancer progression. The trial seeks patients whose cancer has not improved with other treatments and has metastasized. Participants should have tried standard therapies without success and have cancer that cannot be cured or controlled with current options. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this potentially groundbreaking therapy.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking any strong drugs that affect a specific liver enzyme (P450 CYP3A4) at least 5 half-lives before starting the trial. However, you can continue hormone replacement therapy and stable hormonal treatments for certain cancers.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of temsirolimus and metformin has been tested for safety in people with advanced cancer. Studies found that this combination was generally safe for those with advanced endometrial cancer, with no unexpected side effects, indicating good tolerance.

Adding metformin to temsirolimus did not cause severe side effects. While any treatment may have some side effects, this combination appears manageable for most people. Prospective participants can find reassurance in the fact that previous studies have shown the treatment to be well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of Temsirolimus and Metformin for advanced cancer because it targets the disease in a unique way. Temsirolimus inhibits a protein involved in cancer cell growth, while Metformin, commonly known for its use in diabetes, may enhance the body's response to this treatment by affecting cancer metabolism. Unlike standard cancer treatments that often focus solely on inhibiting cell division, this combination has the potential to disrupt cancer growth through multiple pathways, offering a new approach that might improve outcomes for patients with resistant forms of cancer.

What evidence suggests that temsirolimus and metformin might be an effective treatment for advanced cancer?

Research has shown that using temsirolimus and metformin together might help treat advanced cancer. In this trial, participants will receive a combination of temsirolimus, which stops cancer cells from growing by blocking certain necessary enzymes, and metformin, a common diabetes medication that might also slow or stop cancer growth. One study found that 41% of patients receiving this combination did not experience cancer progression for six months. This suggests that these drugs together might help slow cancer spread in some patients. ^{1 3 4 6 7}

Who Is on the Research Team?

Aung Naing, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic cancer that's resistant to standard treatments, relapsed, or has no effective standard therapy. Participants must have stable vital signs and organ function, not be pregnant or breastfeeding, agree to use contraception, and be able to take oral medication. They should be recovered from previous therapies and not on certain drugs affecting liver enzymes.

Inclusion Criteria

Creatinine < 1.5 mg/dl in males and < 1.4 in females

Ability to understand and willingness to sign a written informed consent document

Platelets >= 75,000/mL

Exclusion Criteria

I have severe heart failure.

I haven't had a stroke, heart attack, or severe chest pain in the last 6 months.

I have not had major surgery in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive temsirolimus and metformin. Cycle 1 includes a 2-week metformin titration period followed by 4 weeks of combined treatment. Subsequent cycles are 4 weeks long.

6 weeks for Cycle 1, 4 weeks for subsequent cycles

Weekly visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment. Includes imaging every 8 weeks and more frequently if needed.

4 weeks

Visits every 8 weeks for imaging

End-of-Study Visit

Final assessments including physical exam, performance status, and routine tests within 30 days after last dose.

What Are the Treatments Tested in This Trial?

Interventions

• Metformin
• Temsirolimus

Trial Overview The study tests the combination of temsirolimus (an enzyme blocker) and metformin hydrochloride (a diabetes drug potentially slowing cancer growth) in patients with advanced cancers. It aims to determine the safest doses while observing how well these drugs work together against tumor cells.

How Is the Trial Designed?

Group I: Temsirolimus + Metformin Experimental Treatment 2 Interventions

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.

Metformin is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Glucophage for:

• Type 2 diabetes

Approved in United States as Glucophage for:

• Type 2 diabetes

Approved in Canada as Glucophage for:

• Type 2 diabetes

Approved in Japan as Glucophage for:

• Type 2 diabetes

Approved in China as Glucophage for:

• Type 2 diabetes

Approved in Switzerland as Glucophage for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39787747/

A phase I study of temsirolimus in combination with metformin ... In this phase 1 clinical trial we hypothesized that combining metformin with temsirolimus would potentiate the antitumor activity against advanced or recurrent ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S009082582401237X

A phase I study of temsirolimus in combination with ... The combination of temsirolimus and metformin was safe in patients with advanced endometrial cancer. · Adding metformin to temsirolimus resulted in an objective ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01529593

Study Details | NCT01529593 | Temsirolimus in ... 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 ...

4. onclive.com onclive.com/view/temsirolimus-metformin-combo-generates-forward-looking-questions-in-endometrial-cancer

Temsirolimus/Metformin Combo Generates Forward ... At 6 months in that trial, 41% [95% CI, 27%-54%] of patients were progression free. There are patients who benefit from the combination [of ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5978416/

Phase I Dose Escalation Study of Temsirolimus in ... In conclusion, the combination of temsirolimus and metformin was safe and had modestly promising effectiveness in this cohort of heavily pre- ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01529593

Study Details | NCT01529593 | Temsirolimus in ... 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 ...

7. aacrjournals.org aacrjournals.org/mct/article/22/12_Supplement/A121/730314/Abstract-A121-Temsirolimus-in-combination-with

Abstract A121: Temsirolimus in combination with metformin in ... Conclusions: In conclusion, the combination of temsirolimus with metformin had modest anti-tumor activity in patients with advanced or recurrent ...