Everolimus + Letrozole + Metformin for Endometrial Cancer
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial tests whether a combination of three medications—everolimus, letrozole, and metformin—can control endometrial cancer that has returned or isn't responding to other treatments. Everolimus (also known as Afinitor, Votubia, or Zortress) aims to stop cancer growth by blocking certain proteins in cancer cells. Letrozole reduces estrogen to slow cancer cell growth, and metformin, commonly used for diabetes, may help by lowering insulin levels. People with endometrial cancer that hasn't improved with standard treatments might be suitable candidates. The trial also evaluates the safety of this drug combination for participants. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.
Do I have to stop taking my current medications to join the trial?
The trial requires that you stop all other anti-tumor therapies for at least four weeks before joining. If you are on chronic systemic corticosteroids or other immunosuppressive agents, you cannot participate. Metformin must be paused for 24 hours before and 48 hours after imaging with IV contrast.
Is there any evidence suggesting that this trial's treatments are likely to be safe?
Research has shown that the combination of everolimus, letrozole, and metformin has been tested in women with advanced or recurrent endometrial cancer. Previous studies suggest that this drug combination is generally well-tolerated.
Everolimus blocks proteins that help cancer grow. Letrozole lowers estrogen levels, potentially slowing cancer cell growth. Metformin, commonly used for diabetes, can reduce insulin levels, which may also slow cancer progression.
While this treatment is still under study, the individual components are well-known. Everolimus and letrozole are used in other cancer treatments, and metformin is a widely used diabetes medication. This provides some confidence about their safety, although the full effects of the combination are still being researched.12345Why are researchers excited about this trial's treatments?
Researchers are excited about the combination of Everolimus, Letrozole, and Metformin for treating endometrial cancer because it targets the cancer in a novel way. Unlike standard treatments that often rely on surgery and traditional chemotherapy, this combination uses Everolimus to inhibit a pathway known as mTOR, which is crucial for cancer cell growth and survival. Letrozole, an aromatase inhibitor, reduces estrogen levels, slowing cancer progression, while Metformin, commonly used for diabetes, may enhance the effectiveness of these drugs by affecting cancer metabolism. This multi-pronged approach could offer a more effective strategy in managing endometrial cancer, especially for patients whose cancer is resistant to current therapies.
What evidence suggests that this combination treatment could be effective for endometrial cancer?
This trial will study the combination of everolimus, letrozole, and metformin for treating recurrent endometrial cancer. Studies have shown that everolimus and letrozole together show promise in treating this condition. Everolimus blocks a protein in cancer cells that aids their growth, while letrozole reduces estrogen production, potentially slowing cancer cell growth. Metformin, a common diabetes medication, lowers insulin levels, which might also help slow or stop cancer growth. Early research suggests this combination may effectively control endometrial cancer. Although still under study, the results so far are hopeful.12467
Who Is on the Research Team?
Pamela T. Soliman
Principal Investigator
M.D. Anderson Cancer Center
Are You a Good Fit for This Trial?
This trial is for adults with advanced or recurrent endometrial carcinoma that's resistant to standard treatments. Participants can have had no more than two prior chemo regimens, must not be pregnant or of child-bearing potential, and should have adequate organ function. They cannot join if they've had other cancers (except certain skin cancers) in the past 3 years, known hypersensitivity to everolimus, uncontrolled brain metastases, severe liver impairment, active infections, or are on immunosuppressants.Inclusion Criteria
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Lead-in Period
Participants take Metformin alone for 7-10 days before starting Cycle 1
Treatment
Participants receive Everolimus, Letrozole, and Metformin in 4-week cycles
End-of-Treatment
Final assessments after the last dose of study drugs
Follow-up
Participants are monitored for safety and effectiveness after treatment
What Are the Treatments Tested in This Trial?
Interventions
- Everolimus
- Letrozole
- Metformin
Everolimus is already approved in United States, European Union for the following indications:
- Advanced renal cell carcinoma
- Subependymal giant cell astrocytoma
- Progressive neuroendocrine tumors of pancreatic origin
- Advanced hormone receptor-positive, HER2-negative breast cancer
- Tuberous sclerosis complex-associated partial-onset seizures
- Subependymal giant cell astrocytoma
- Renal angiomyolipoma
- Tuberous sclerosis complex-associated partial-onset seizures
- Prevention of organ rejection in kidney transplant patients
Find a Clinic Near You
Who Is Running the Clinical Trial?
M.D. Anderson Cancer Center
Lead Sponsor
National Cancer Institute (NCI)
Collaborator
Novartis
Industry Sponsor
Vasant Narasimhan
Novartis
Chief Executive Officer since 2018
MD from Harvard Medical School, Bachelor's in Biological Sciences from University of Chicago, Master's in Public Policy from John F. Kennedy School of Government
Shreeram Aradhye
Novartis
Chief Medical Officer since 2022
MD from Yale University, MSc in Clinical Epidemiology from University of Pennsylvania