Everolimus + Letrozole +/- Ribociclib for Endometrial Cancer
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial explores the effectiveness of combining everolimus (also known as Afinitor, Votubia, or Zortress) and letrozole (also known as Femara), with or without ribociclib (also known as Kisqali), in treating endometrial cancer that has spread or returned. Ribociclib may inhibit tumor growth by blocking certain enzymes, while everolimus and letrozole are known to slow or stop cancer cell growth and spread. The researchers aim to determine if adding ribociclib can enhance treatment effectiveness. Suitable candidates for this trial include individuals with endometrial cancer that has spread or recurred and has not responded to other treatments. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.
Do I need to stop my current medications to join the trial?
Yes, you will need to stop taking certain medications before joining the trial. Specifically, you must be off all other anti-tumor therapies for at least four weeks and stop hormonal agents for 10 days before starting the study. Additionally, some medications like strong inducers or inhibitors of CYP3A4/5 and certain herbal preparations must be discontinued 7 days prior to the study.
Is there any evidence suggesting that this trial's treatments are likely to be safe?
Research shows that the combination of ribociclib, everolimus, and letrozole is under evaluation for its effectiveness in treating endometrial cancer. Studies have found that ribociclib and letrozole together show promise in treating certain types of this cancer.
For the combination of everolimus and letrozole, research indicates it is generally safe, with most patients handling the treatment well. Some studies reported positive results, with the treatment slowing or stopping the cancer in some patients.
Overall, these combinations have been studied for safety and are generally well-tolerated. However, like any treatment, side effects can occur. It is important to consult the research team to understand what to expect.12345Why are researchers excited about this trial's treatments?
Researchers are excited about these treatments for endometrial cancer because they combine targeted therapies that work in unique ways compared to standard treatments like chemotherapy and hormone therapy. Everolimus is an mTOR inhibitor that helps stop cancer cell growth by blocking a crucial cellular pathway, while Letrozole is an aromatase inhibitor that reduces estrogen levels, starving the cancer cells that rely on this hormone. In one arm, the combination with Ribociclib, a CDK4/6 inhibitor, adds an extra layer of attack by interrupting the cancer cell cycle, potentially enhancing effectiveness. This multi-pronged approach aims to tackle cancer more effectively and with potentially fewer side effects than traditional treatments.
What evidence suggests that this trial's treatments could be effective for endometrial cancer?
Research has shown that using everolimus and letrozole together, which participants in this trial may receive, can help treat endometrial cancer. Studies have found that about 28% to 32% of patients respond to this treatment, with some seeing a 45% response if their tumors have specific traits. Everolimus stops cancer cells from growing and may also block the blood vessels that supply tumors. Another treatment arm in this trial includes adding ribociclib, which inhibits enzymes needed for cell growth and might enhance these results. Although ribociclib is still being tested with these drugs, the combination is thought to potentially improve treatment for advanced or recurrent endometrial cancer.15678
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 patients with advanced or recurrent endometrial carcinoma who have had no more than two prior chemotherapy regimens and are not currently pregnant or breastfeeding. They must be able to provide informed consent, have a GOG performance status of 0 to 1, and meet specific blood count and organ function criteria. Prior radiation therapy and letrozole treatment are acceptable under certain conditions.Inclusion Criteria
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive ribociclib, everolimus, and letrozole or everolimus and letrozole alone on a 28-day cycle
Follow-up
Participants are monitored for safety and effectiveness after treatment completion
What Are the Treatments Tested in This Trial?
Interventions
- Everolimus
- Letrozole
- Ribociclib
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