NCT03675893

RESOLVE: Abemaciclib + Letrozole +/- Metformin, Zotatifin, or Gedatolisib in Endometrial or Low-Grade Serous Ovarian Cancer

RESOLVE: letRozole abEmaciclib combinationS in endOmetriaL and oVarian cancEr: A Multi-Cohort Phase 2 Study of Letrozole/Abemaciclib Alone and in Combination With Metformin, Zotatifin and Gedatolisib

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 180 (estimated)
• Sponsor: Dana-Farber Cancer Institute · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This research study is studying a combination of targeted therapies as a possible treatment for estrogen-receptor positive (ER+) endometrial cancer and low-grade serous ovarian cancer. The drugs involved in this study are: * Abemaciclib (also known as Verzenio™) * Letrozole (also known as Femara®) * Metformin (also known as Glucophage®) * Zotatifin (also known as eFT226) * Gedatolisib (also known as PF-05212384)

Detailed description

This is a Phase II clinical trial. Phase II clinical trials evaluate whether investigational drugs are effective against a specific disease. "Investigational" means that the drugs are being studied. The U.S. Food and Drug Administration (FDA) has not approved abemaciclib or letrozole for your specific disease but it has been approved for other uses. The FDA has approved metformin for diabetes but is considered investigational for its use in cancer. The FDA has not approved zotatifin as a treatment for any disease. The FDA has not approved gedatolisib as a treatment for any disease. Abemaciclib is a cyclin-dependent kinase (CDK) inhibitor. CDK inhibitors work to stop cancer cell growth. Letrozole is a hormonal therapy that works by lowering the production of estrogen in your body. Estrogen may help to stimulate cancer cells to grow, so lowering the levels of estrogen in your body may work to slow cancer cell growth. Metformin is an antihyperglycemic drug most commonly used to lower the amount of blood sugar in the blood and increase the body's sensitivity to insulin. Metformin also works on cancer cells to stop cancer cell growth and promote cancer cell death. Zotatifin is a selective eukaryotic initiation factor 4A (eIF4A) inhibitor. Selective eIF4A inhibition works by stopping cancer cell growth and enhancing CDK inhibition. Gedatolisib is a PI3K/AKT/mTOR (PAM) pathway inhibitor. PAM inhibitors work to stop cancer cell growth. PAM inhibition has been shown to enhance CDK inhibitors and hormonal therapy, like abemaciclib and letrozole. In this research study, we are hoping to learn whether the combinations of abemaciclib and letrozole alone, or with metformin, zotatifin or gedatolisib are effective at slowing or stopping endometrial and/or ovarian cancer cell growth.

Conditions

• Endometrial Cancer
• Ovarian Cancer

Interventions

Type	Name	Description
DRUG	Letrozole	Letrozole is a hormonal therapy that works by lowering the production of estrogen in the body.
DRUG	Abemaciclib	Abemaciclib is a cyclin-dependent kinase (CDK) inhibitor.
DRUG	LY3023414	LY3023414 is a potent selective inhibitor of the class I PI3K isoforms, mTOR, and DNA-PK.
DRUG	Metformin	Metformin inhibits mitochondrial adenosine-5'-triphosphate (ATP) synthesis, resulting in activation of the AMPK (5' AMP-activated protein kinase) pathway through LKB1, eventually causing inhibition of the mTOR pathway and subsequent reduction in protein synthesis and cellular proliferation.
DRUG	Zotatifin	Zotatifin is a selective eukaryotic initiation factor 4A (eIF4A) inhibitor.
DRUG	Gedatolisib	Gedatolisib is a PI3K/AKT/mTOR (PAM) pathway inhibitor.

Timeline

• Start date: 2018-12-24
• Primary completion: 2028-08-01
• Completion: 2031-08-01
• First posted: 2018-09-18
• Last updated: 2025-06-15

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study