RESOLVE: A Multi-Cohort Phase 2 Study of Letrozole/Abemaciclib Alone and in Combination With Metformin and Gedatolisib
Dana-Farber Cancer Institute
Summary
This research study is studying a combination of targeted therapies as a possible treatment for estrogen-receptor positive (ER+) endometrial cancer. The drugs involved in this study are: * Abemaciclib (also known as Verzenio™) * Letrozole (also known as Femara®) * Metformin (also known as Glucophage®) * Gedatolisib (also known as PF-05212384)
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 gedatolisib as a treatment for any disease. Abemaciclib is a cyclin-dependent kinase (CDK) inhibitor. CDK inhibitors w…
Eligibility
- Age range
- 18+ years
- Sex
- Female
- Healthy volunteers
- No
Inclusion Criteria: * Participants must have cytologically or histologically confirmed endometrial cancer that is recurrent or metastatic and/or resistant to standard therapies, or for which no standard therapy is available. Participants enrolled in the second stage of Cohort 1A, or into Cohort 3, 6 and 7, must have histologically confirmed either i) endometrioid endometrial cancer or ii) endometrial carcinosarcoma with endometrioid epithelial component * Participants must have ER-positive disease, defined as ≥ 1 percent of tumor cell nuclei being immunoreactive by immunohistochemistry (IHC).…
Interventions
- DrugLetrozole
Letrozole is a hormonal therapy that works by lowering the production of estrogen in the body.
- DrugAbemaciclib
Abemaciclib is a cyclin-dependent kinase (CDK) inhibitor.
- DrugLY3023414
LY3023414 is a potent selective inhibitor of the class I PI3K isoforms, mTOR, and DNA-PK.
- DrugMetformin
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.
- DrugGedatolisib
Gedatolisib is a PI3K/AKT/mTOR (PAM) pathway inhibitor.
Locations (3)
- Massachusetts General Hospital Cancer CenterBoston, Massachusetts
- Beth Israel Deaconess Medical Center (BIDMC)Boston, Massachusetts
- Dana Farber Cancer InstituteBoston, Massachusetts