NCT03008408

A Phase II, Two-Arm Study of Everolimus and Letrozole, +/- Ribociclib (Lee011) in Patients With Advanced or Recurrent Endometrial Carcinoma

A Phase II, Randomized Two-Arm Study of Everolimus and Letrozole, +/- Ribociclib (LEE011) in Patients With Advanced or Recurrent Endometrial Carcinoma

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 90 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial studies how well everolimus and letrozole with or without ribociclib work in treating participants with endometrial cancer that has spread to other areas of the body or has come back. Ribociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs such as everolimus and letrozole have been shown to be effective at stopping tumor growth either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ribociclib, everolimus, and letrozole may work better than everolimus and letrozole in treating participants with endometrial cancer.

Detailed description

PRIMARY OBJECTIVE: I. To determine if the addition of ribociclib (LEE011) to everolimus and letrozole improves progression free survival in patients with advanced or recurrent endometrial carcinoma. SECONDARY OBJECTIVES: I. To determine clinical benefit and the median duration of progression-free survival (PFS) and overall survival (OS) in patients with advanced or recurrent endometrial carcinoma treated with ribociclib (LEE011), everolimus and letrozole versus everolimus and letrozole alone. II. To determine the frequency and severity of toxicities associated with ribociclib (LEE011), everolimus (RAD001), and letrozole in this cohort of patients. III. To determine the presence of a CTNNB1 mutation is associated with response to ribociclib (LEE011), everolimus (RAD001), and letrozole. IV. To determine if liquid biopsies at baseline and 8 weeks correlate with presence of a tissue mutation or response to therapy. EXPLORATORY OBJECTIVE: I. To examine the pharmacokinetic and pharmacodynamic effects of ribociclib in patients with advanced or recurrent endometrial carcinoma. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive ribociclib orally (PO) once daily (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. ARM II: 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. After completion of study treatment, participants are followed up at 30 days and then every 3 months.

Conditions

• Recurrent Endometrial Carcinoma
• Recurrent Endometrial Endometrioid Adenocarcinoma
• Refractory Endometrial Carcinoma
• Refractory Endometrial Endometrioid Adenocarcinoma
• Stage III Uterine Corpus Cancer AJCC v8
• Stage IIIA Uterine Corpus Cancer AJCC v8
• Stage IIIB Uterine Corpus Cancer AJCC v8
• Stage IIIC Uterine Corpus Cancer AJCC v8
• Stage IIIC1 Uterine Corpus Cancer AJCC v8
• Stage IIIC2 Uterine Corpus Cancer AJCC v8
• Stage IV Uterine Corpus Cancer AJCC v8
• Stage IVA Uterine Corpus Cancer AJCC v8
• Stage IVB Uterine Corpus Cancer AJCC v8

Interventions

Type	Name	Description
DRUG	Everolimus	Given PO
DRUG	Letrozole	Given PO
DRUG	Ribociclib	Given PO

Timeline

• Start date: 2017-08-18
• Primary completion: 2028-08-31
• Completion: 2028-08-31
• First posted: 2017-01-02
• Last updated: 2026-02-11

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study