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

NCT03008408 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2015-0961NCI-2018-01284
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Recurrent Endometrial Carcinoma; Recurrent Endometrial Endometrioid Adenocarcinoma; 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; Refractory Endometrial Carcinoma

Outcome Measures

Primary Outcomes (1)

• Clinical benefit rate (CBR)

  Per Response Evaluation Criteria in Solid Tumors version 1.1. This will be determined by combining the complete response rate, partial response rate, and stable disease rate. Response will be evaluated by repeat imaging (computed tomography or magnetic resonance imaging). Fisher's exact test will be used to compare patients with/without CTNNB1 mutation with respect to CBR.

  At 8 weeks

Study Arms (2)

Arm I (ribociclib, everolimus, letrozole)

EXPERIMENTAL

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.

Drug: Everolimus; Drug: Letrozole; Drug: Ribociclib

Arm II (everolimus, letrozole)

EXPERIMENTAL

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.

Drug: Everolimus; Drug: Letrozole

Interventions

Everolimus DRUG

Given PO

Also known as: 42-O-(2-Hydroxy)ethyl Rapamycin, Afinitor, Certican, RAD 001, RAD001, Votubia, Zortress

Arm I (ribociclib, everolimus, letrozole); Arm II (everolimus, letrozole)

Letrozole DRUG

Given PO

Also known as: CGS 20267, Femara

Arm I (ribociclib, everolimus, letrozole); Arm II (everolimus, letrozole)

Ribociclib DRUG

Given PO

Also known as: Kisqali, LEE-011, LEE011

Arm I (ribociclib, everolimus, letrozole)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has signed the informed consent (ICF) prior to any screening procedures being performed and is able to comply with protocol requirements.
• Patients must have histologically-confirmed endometrial carcinoma (endometrioid and mixed endometrioid tumors, any grade).
• Patients must have advanced or recurrent disease that is refractory to curative treatment based on imaging or clinical exam.
• Patient must consent to allow for a baseline tumor biopsy. Tumor material from biopsies done before the screening period are acceptable if the biopsy was performed within 3 months prior to the planned treatment start and no other systemic cancer therapy was administered in the interim. If a biopsy is performed and the specimen is considered non-diagnostic, does not have enough tissue, or the biopsy is deemed infeasible to perform, this does not prevent the patient from proceeding with the treatment
• Patients must have had no more than two prior chemotherapeutic regimens for recurrent endometrial carcinoma. Chemotherapy administered in conjunction with primary radiation as a radio-sensitizer is not counted as a prior treatment for recurrent or advanced disease.
• Prior radiation therapy of any kind is allowed.
• Prior treatment with letrozole is allowed if the patient meets the washout period of 10 days.
• All patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 defined as at least one "target lesion" that can be accurately measured in at least one dimension (\>= 10 mm longest dimension to be recorded; Lymph nodes must be \>= 15 mm per short axis). Each lesion must be \> 20 mm when measured by palpation or conventional imaging techniques (computed tomography \[CT\] or magnetic resonance imaging \[MRI\] - based on primary physician preference) or \> 10 mm with spiral CT scan. Measurable lesions must be at least 2 times the slice thickness in millimeters. Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented. Ascites and pleural effusions are not considered measurable disease. If the measurable disease is confined to a solitary lesion, its neoplastic nature should be confirmed by cytology/histology.
• Patients must not be pregnant, breastfeeding or of child-bearing potential. Patients are considered not of child bearing potential if they are surgically sterile (they have undergone a total hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal for greater than 12 months (if patient is uncertain of amenorrhea for 12 months, a pregnancy test will be done to confirm pregnancy status). Patients in whom ovaries are present and were not previously menopausal at the time of hysterectomy, should have a serum estradiol \< 10 pm/mL to confirm ovarian senescence.
• Patients must be off all other anti-tumor therapies (including immunologic agents) for at least four weeks prior to study registration. Patients on hormonal agents require a washout for 10 days.
• Gynecologic Oncology Group (GOG) performance status of 0 to 1.
• Absolute neutrophil count \>= 1.5 x 10\^9/L (at screening).
• Platelets \>= 100 x 10\^9/L (at screening).
• Hemoglobin \>= 9.0 g/dL (at screening).
• International normalized ratio (INR) =\< 1.5 (at screening).

You may not qualify if:

• Patients who have uterine sarcomas, carcinosarcomas, serous tumors (any component) or pure clear cell carcinomas.
• Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.)
• Patient has not recovered from all toxicities related to prior anticancer therapies to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 grade =\< 1 (exception to this criterion: patients with grade 1 taxane-induced neuropathy, any grade of alopecia, amenorrhea or other toxicities not considered a safety risk for the patient as per investigator's discretion are allowed to enter the study).
• 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).
• Participation in other studies involving investigational drug(s) within 30 days prior to randomization or within 5 half-lives of the investigational product (whichever is longer) or participation in any other type of medical research judged not to be scientifically or medically compatible with this study.
• Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical, short duration (\< 5 days) of systemic corticosteroids, eye drops, local injections, or inhaled corticosteroids are allowed.
• Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period. Close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus. Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, bacillus Calmette-guerin (BCG), yellow fever, varicella and TY21a typhoid vaccines.
• Patients with central nervous system (CNS) involvement unless they meet all of the following criteria:
• At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment.
• Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases.
• Patient has a concurrent malignancy or malignancy within 3 years prior to starting study drug, with the exception of adequately treated, basal or squamous cell carcinoma curatively resected cervical cancer in situ.
• Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, may cause unacceptable safety risks, contraindicate patient participation in the clinical study or compromise compliance with the protocol (e.g. chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled fungal, bacterial or viral infections, etc.).
• Patient has a known history of human immunodeficiency virus (HIV) infection (testing not mandatory).
• Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities, including any of the following:
• History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to screening.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (2)

Lyndon Baines Johnson General Hospital

Houston, Texas, 77026-1967, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

Everolimus; Letrozole; ribociclib

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Pamela T Soliman

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 28, 2016
• First Posted: January 2, 2017
• Study Start: August 18, 2017
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): August 31, 2028
• Last Updated: February 11, 2026

Record last verified: 2026-02

Locations

US (2)