What side effects are associated with this type of intervention?

Common side effects of Ribociclib (CDK4/6 inhibitor) include neutropenia, liver enzyme abnormalities, and fatigue. Everolimus (mTOR inhibitor) is often associated with stomatitis, infections, rash, fatigue, and diarrhea. Letrozole (aromatase inhibitor) can cause hot flashes, joint pain, and an increased risk of osteoporosis. When used in combination, these drugs may have overlapping toxicities, and patients should be monitored for compounded side effects such as increased risk of infections and fatigue.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of endometrial cancer, though specific approvals for combinations like Ribociclib (CDK4/6 inhibitor), Everolimus (mTOR inhibitor), and Letrozole (aromatase inhibitor) are not detailed. Generally, treatments for endometrial cancer include hormonal therapies such as progestins and aromatase inhibitors, chemotherapy agents like carboplatin and paclitaxel, and targeted therapies including mTOR inhibitors like Everolimus. The combination of these specific drugs is currently being studied to evaluate their efficacy in treating advanced or recurrent endometrial cancer.

What other types of research exist?

Promising novel alternatives for endometrial cancer treatment in 2024 may include: 1) PARP inhibitors such as Olaparib, which have shown efficacy in BRCA-mutated cancers; 2) Immune checkpoint inhibitors like Pembrolizumab, particularly for mismatch repair-deficient tumors; 3) Angiogenesis inhibitors such as Bevacizumab, which have been effective in other gynecologic cancers; and 4) WEE1 inhibitors like Adavosertib, which are being evaluated in combination with chemotherapy. These alternatives target different mechanisms and may offer new hope for patients with advanced or recurrent endometrial cancer.

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mTOR inhibitor

Everolimus + Letrozole +/- Ribociclib for Endometrial Cancer

Phase 2

Waitlist Available

Led By Pamela T Soliman

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Estimated glomerular filtration rate (eGFR) >= 30mL/min/1.73m^2 (at screening) according to the Modification of Diet in Renal Disease (MDRD) formula.

Patients must have advanced or recurrent disease that is refractory to curative treatment based on imaging or clinical exam.

Must not have

Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered as major surgery).

Patients with a known hypersensitivity to ribociclib or everolimus or to its excipients.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at 8 weeks

Awards & highlights

Approved for 10 Other Conditions

No Placebo-Only Group

All Individual Drugs Already Approved

Summary

This trial is testing a new drug combination for advanced or recurrent endometrial cancer. It targets patients whose cancer has spread or returned. The treatment works by blocking enzymes needed for cancer cell growth and by stopping the cells from dividing or spreading. Anlotinib is a new drug that targets multiple aspects of cancer growth.

Who is the study for?

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.

What is being tested?

The study is testing the effectiveness of everolimus combined with letrozole, with or without ribociclib, in treating endometrial cancer that has spread or returned. Ribociclib blocks enzymes needed for cell growth while everolimus and letrozole work by killing cells, stopping division, or preventing spread.

What are the potential side effects?

Potential side effects include risks associated with blocking enzyme functions which may affect tumor growth but also normal cell processes. This can lead to fatigue, digestive issues, changes in blood counts affecting overall health, possible heart rhythm problems due to QT interval prolongation from ribociclib.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My kidney function, measured by eGFR, is adequate.

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My disease cannot be cured with treatment and is getting worse.

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My liver function tests are within the required range.

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My kidney function is within the normal range.

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I am fully active or restricted in physically strenuous activity but can do light work.

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I have at least one tumor that can be measured and has not been previously treated with radiation.

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I haven't taken any cancer treatments or immunologic agents for the last 4 weeks.

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I have been diagnosed with a specific type of uterine cancer.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I haven't had major surgery or recovered from its major side effects within the last 14 days.

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I am allergic to ribociclib, everolimus, or their ingredients.

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I am not taking strong CYP3A4/5 drugs, certain supplements, hormone therapies, or warfarin.

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I do not have serious heart problems or abnormal heart rhythms.

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I have severe liver disease.

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I have previously been treated with an mTOR inhibitor.

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I do not have major stomach or bowel problems that could affect how I absorb medication.

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My cancer is a specific type of uterine cancer.

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I don't have Long QT syndrome, sudden death in family, or risk factors for Torsades de Pointe.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ at 8 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~at 8 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and at 8 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Clinical benefit rate (CBR)

Awards & Highlights

Approved for 10 Other Conditions

This treatment demonstrated efficacy for 10 other conditions.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Arm II (everolimus, letrozole)Experimental Treatment2 Interventions

Patients receive everolimus PO QD and letrozole PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (ribociclib, everolimus, letrozole)Experimental Treatment3 Interventions

Patients receive ribociclib PO QD, everolimus PO QD, and letrozole PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Letrozole

FDA approved

Ribociclib

FDA approved

Everolimus

FDA approved

0 / 17Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Ribociclib, Everolimus, and Letrozole are targeted therapies used in treating endometrial cancer. Ribociclib inhibits CDK4/6 enzymes, preventing tumor cell proliferation. Everolimus targets the mTOR pathway, reducing cell growth and survival. Letrozole lowers estrogen levels, slowing the growth of hormone receptor-positive cancer cells. These mechanisms are crucial for selecting effective treatments, particularly for advanced or recurrent endometrial cancer, offering a more personalized and potentially more effective approach to managing the disease.

Phase Ib Dose-escalation/Expansion Trial of Ribociclib in Combination With Everolimus and Exemestane in Postmenopausal Women with HR+, HER2- Advanced Breast Cancer.Phase II study of everolimus and letrozole in patients with recurrent endometrial carcinoma.Hormonal therapy in advanced or recurrent endometrial cancer.