AzTrials
AzTrials

Recurrent Endometrial CarcinomaPhase 2NCT03008408

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

A Phase 2 study testing Everolimus, Letrozole and Ribociclib in people with Recurrent Endometrial Carcinoma and Recurrent Endometrial Endometrioid Adenocarcinoma, run by M.D. Anderson Cancer Center at 2 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Everolimus, Letrozole and Ribociclib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
90 participants
Where
2 sitesUnited States
Study dates
18 Aug 2017to 31 Aug 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 22Show fewer
  • 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).
  • Serum creatinine =< 1.5 mg/dL or creatinine clearance >=50 mL/min (at screening).
  • Estimated glomerular filtration rate (eGFR) >= 30mL/min/1.73m^2 (at screening) according to the Modification of Diet in Renal Disease (MDRD) formula.
  • In the absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x upper limit of normal (ULN). If the patient has liver metastases, ALT and AST < 5 x ULN (at screening).
  • Total bilirubin < ULN; or total bilirubin =< 3.0 x ULN or direct bilirubin =< 1.5 x ULN in patients with well-documented Gilbert's syndrome (at screening).
  • Fasting serum cholesterol =< 240 mg/dL or =< 7.75 mmol/L and fasting triglycerides =< 2.5 x ULN (at screening).
  • NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.
  • Patient with available standard 12-lead electrocardiography (ECG) with the following parameters at screening: a. Corrected QT interval by Fridericia's formula (QTcF) interval at screening < 450 msec (using Fridericia's correction). b. Resting heart rate 50-100 beats per minute (bpm).

Who cannot join

  • 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.
Show all 37Show fewer
  • 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.
  • History of documented congestive heart failure (New York Heart Association functional classification III-IV).
  • Documented cardiomyopathy.
  • Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening.
  • Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g. bifascicular block, Mobitz type II and third-degree AV block).
  • Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
  • Risk factors for Torsades de Pointe (TdP) including uncorrected hypocalcemia, hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia.
  • Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued (within 5 half-lives or 7 days prior to starting study drug) or replaced by safe alternative medication.
  • Inability to determine the QT interval on screening (QTcF, using Fridericia's correction).
  • Systolic blood pressure (SBP) > 160 mmHg or < 90 mmHg at screening.
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study medication (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection associated with malabsorption).
  • Patient is currently receiving any of the following medications and cannot be discontinued 7 days prior to starting study drug:
  • Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit hybrids, pummelos, star-fruit, and Seville oranges.
  • That have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5.
  • Herbal preparations/medications, dietary supplements.
  • Hormone replacement therapy, topical estrogens (including any intra-vaginal preparations), megestrol acetate and selective estrogen-receptor modulators (e.g. raloxifene).
  • Patient is currently receiving warfarin or other coumarin-derived anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH) or fondaparinux is allowed.
  • Liver disease such as cirrhosis or severe hepatic impairment (patient with a Child-Pugh score B or C).
  • Note: A detailed assessment of hepatitis B/C medical history and risk factors must be done at screening for all patients. Hepatitis B virus (HBV) deoxyribonucleic acid (DNA) and hepatitis C virus (HCV) ribonucleic acid (RNA) polymerase chain reaction (PCR) testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection.
  • Patients who have received prior treatment with an mTOR inhibitor (e.g., sirolimus, temsirolimus, everolimus).
  • Patients with a known hypersensitivity to ribociclib or everolimus or to its excipients.
  • History of noncompliance to medical regimens.
  • Patients unwilling to or unable to comply with the protocol.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Lyndon Baines Johnson General Hospital

    Houston, Texas, 77026-1967

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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:

  1. 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.

Being tested
Everolimus, Letrozole, Ribociclib
Medical subject headings
Endometrial Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EverolimusDrug

    Also called 42-O-(2-Hydroxy)ethyl Rapamycin, Afinitor, Certican, RAD 001

    Given PO

  • LetrozoleDrug

    Also called CGS 20267, Femara

    Given PO

  • RibociclibDrug

    Also called Kisqali, LEE-011, LEE011

    Given PO

Study groups in NCT03008408
Study groupRoleWhat they receive
Arm I (ribociclib, everolimus, letrozole)ExperimentalPatients 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.
Receives: Drug: Everolimus; Drug: Letrozole; Drug: Ribociclib
Arm II (everolimus, letrozole)ExperimentalPatients 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.
Receives: Drug: Everolimus; Drug: Letrozole

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: At 8 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jan 2017 (estimated)
  2. Study start18 Aug 2017
  3. Primary completion31 Aug 2028 (estimated)
  4. Study completion31 Aug 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
90 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03008408
Sponsor's protocol ID
2015-0961
Other IDs
NCI-2018-01284, 2015-0961
Status last verified
May 2026
First submitted
28 Dec 2016
Last updated
22 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • How JA, Westin SN, Pham M, Lawson B, Chen M, Tandon N, Yuan Y, Zhang R, Jazaeri AA, Sood AK, Onstad Grinsfelder M, Schmeler KM, Vining DJ, Fix SM, Dai Y, Bowen MB, Lu KH, Yates MS, Broaddus R, Soliman PT. Efficacy of everolimus and letrozole with or without ribociclib in recurrent endometrial cancer: a phase 2 randomized clinical trial. Nat Commun. 2026 Sep 1;17(1):10413. doi: 10.1038/s41467-026-77049-3.

    PubMed 42823426

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Everolimus, Letrozole and Ribociclib in people with Recurrent Endometrial Carcinoma and Recurrent Endometrial Endometrioid Adenocarcinoma, run by M.D. Anderson Cancer Center at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinical benefit rate (CBR) (time frame: At 8 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03008408, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in