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Endometrial CancerPhase 2NCT01797523

A Phase II, Single-Arm Study of RAD001 (Everolimus), Letrozole, and Metformin in Patients With Advanced or Recurrent Endometrial Carcinoma

A Phase 2 study testing Metformin, Letrozole and Everolimus in people with Endometrial Cancer, run by M.D. Anderson Cancer Center at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The goal of this clinical research study is to learn if the combination of everolimus, letrozole, and metformin can help to control recurrent or progressive endometrial cancer. The safety of this drug combination will also be studied. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Endometrial Cancer
What is being tested?
Metformin, Letrozole and Everolimus
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
62 participants
Where
6 sitesUnited States
Study dates
7 Oct 2013to 4 Feb 2026
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have histologically-confirmed advanced or recurrent endometrial carcinoma (endometrioid and mixed tumors, any grade) that is refractory to curative therapy or established treatments
  • Patients must have had no more than two prior chemotherapeutic regimens for recurrent management of 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
  • All patients must have measurable disease per RECIST 1.1 defined as at least one target lesion that can be accurately measured in at least one dimension (>/=10mm 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 (CT or 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 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. 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 or hormonal agents) for at least four weeks prior to study registration.
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  • Age >/= 18 years
  • GOG performance status </= 2
  • Adequate bone marrow function as shown by: ANC >/= 1.5 x 10^9/L, Platelets >/= 100 x 10^9/L, Hb >9 g/dL
  • Adequate liver function as shown by: a. serum bilirubin </= 1.5 x ULN b. ALT and AST </= 2.5x ULN (</= 5x ULN in patients with liver metastases); Adequate renal function:serum creatinine < 1.4mg/dL (per manufacturer, metformin is contraindicated in the presence of renal dysfunction defined as a serum creatinine> 1.4 mg/dL in females and in patients with abnormal clearance) ; Fasting serum cholesterol </= 240 mg/dL OR </=7.75 mmol/L AND fasting triglycerides </= 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication
  • Signed informed consent
  • Prior treatment with letrozole is allowed.

Who cannot join

  • Patients who have uterine sarcomas, carcinosarcomas, any serous histology 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.)
  • Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study
  • Prior treatment with any investigational drug within the preceding 4 weeks
  • Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical 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, BCG, yellow fever, varicella and TY21a typhoid vaccines.
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  • Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
  • Other malignancies within the past 3 years except for basal or squamous cell carcinomas of the skin.
  • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: a. Symptomatic congestive heart failure of New York heart Association Class III or IV; b. Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease; c. Severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air; d. Active (acute or chronic) or uncontrolled severe infections
  • CONTINUED FROM 10 - e. Liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C). Note: A detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening for all patients. HBV DNA and HCV RNA 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; f. A known history of HIV seropositivity; g. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection); h. Patients with an active, bleeding diathesis
  • Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. Adequate contraception must be used throughout the trial and for 8 weeks after the last dose of study drug, by both sexes. (Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of everolimus)
  • Patients who have received prior treatment with an mTOR inhibitor (e.g., sirolimus, temsirolimus, everolimus).
  • Patients with a known hypersensitivity to everolimus or other rapamycins (e.g., sirolimus, temsirolimus) or to its excipients
  • History of noncompliance to medical regimens
  • Patients unwilling to or unable to comply with the protocol.
  • Patients with isolated recurrences (vaginal, pelvic, or paraaortic) that are amenable to potentially curative treatment with radiation therapy or surgery.
  • Patients with acute or chronic metabolic acidosis, lactic acidosis, or ketoacidosis. Note: during the study, metformin must be discontinued for 24 hours before and 48 hours after imaging involving IV contrast to minimize risk of lactic acidosis.
  • Patients who have hypoglycemia with a value of </= 50 mg/dL

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Memorial City Medical Center

    Houston, Texas, 77024

  • Lyndon B Johnson General Hospital

    Houston, Texas, 77026

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • The Woman's Hospital of Texas

    Houston, Texas, 77054

  • Sacred Heart Health Systems

    Pensacola, Florida, 32504

  • MD Anderson Cooper Cancer Center

    Voorhees Township, New Jersey, 08043

Other trials in United States

About this study

The goal of this clinical research study is to learn if the combination of everolimus, letrozole, and metformin can help to control recurrent or progressive endometrial cancer. The safety of this drug combination will also be studied.

Everolimus is designed to block a protein inside cancer cells that is involved in cancer growth.

Letrozole is designed to block a protein from making estrogen. This may interfere with the growth of cancer cells.

Metformin is commonly used to control blood sugar levels in patients with diabetes. It is designed to lower insulin levels, which may slow or stop the growth of endometrial cancer cells.

Read the detailed description

Study Drug Administration:

If you are found to be eligible to take part in this study and you are not already taking metformin, you will take metformin before you begin the regular study cycles (Cycles 1 and beyond). This will be called "Cycle 0." You will take metformin by mouth 1 time a day on Days 1-4 of Cycle 0 and then 2 times a day (about 12 hours apart) every day after that. You will take metformin for 7-10 days in Cycle 0 before Cycle 1 begins. If you are already taking metformin, you will continue your regular dose and start Day 1 of Cycle 1. If you are already taking metformin but your dose is less than 1000mg/day, your dose will be slowly raised up to the study dose over the course of 7-10 days and then you will start Cycle 1. In Cycles 1 and beyond, all participants will take all 3 drugs at a time. You should take metformin with food.

Starting in Cycle 1, you will take everolimus 1 time a day by mouth at about the same time every day. You should take it either consistently with food every day or consistently without food every day.

Starting in Cycle 1, you will take letrozole 1 time a day by mouth at about the same time every day.

It is very important for you to take the study drugs just as the study doctor tells you. Do not skip any doses unless your study doctor tells you to skip doses. If you throw up after taking the study drugs, you should NOT take another tablet that day. Let your study doctor know that you got sick. If you forget to take the study drugs one day, do not take any extra doses the next day. Call your study doctor and ask for advice.

There are 4 weeks in each cycle (except Cycle 0).

Study Visits:

Every cycle (+/- 10 days):

  • You will have a physical exam, including measurement of your vital signs and weight.
  • Your performance status will be recorded.
  • You will be asked about any side effects you may have had.
  • Blood (about 2 tablespoons) will be drawn for routine tests.
  • If the doctor thinks it is needed, blood (about 1 teaspoon) will be drawn to check for hepatitis.

After Cycles 2, 4, and 6 and then every 3 cycles after that (Cycles 9, 12, 15, and so on) (+/- 10 days):

  • You will have scans such as a CT scan and/or MRI to check the status of the disease.
  • If you have chest disease, you will have a CT scan of the chest.
  • If the disease could be felt in the pelvis at the beginning of the study, you will have a pelvic exam

After every other cycle (Cycles 2, 4, and so on), blood (about 1 teaspoon) will be drawn for routine tests.

Length of Treatment:

You may continue taking the study drugs for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drugs if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over after the follow-up visits.

End-of-Treatment Visit:

Within 4 weeks after the last dose of study drugs:

  • You will have a physical exam, including a pelvic exam and measurement of your vital signs and weight.
  • Your performance status will be recorded.
  • You will be asked about any side effects you may have had.
  • Blood (about 2 tablespoons) will be drawn for routine tests.
  • You will have scans such as a CT scan and/or MRI to check the status of the disease.
  • If you have chest disease, you will have a CT scan of the chest.

Follow-Up:

You will have follow-up visits as often as the doctor thinks is needed. At every visit:

  • You will have a physical exam, including measurement of your vital signs.
  • Your performance status will be recorded.
  • You will be asked about any side effects you may have had.
  • If the doctor thinks it is needed, you will have scans such as a CT scan and/or MRI to check the status of the disease.
  • If you have chest disease, you will have a CT scan of the chest.

As often as the doctor thinks is needed, the study staff will call you to ask about side effects you may have had. These calls should last 5-10 minutes.

.

This is an investigational study. Everolimus is FDA approved and commercially available to treat kidney, breast, and pancreatic cancers. Letrozole is FDA approved and commercially available to treat breast cancer and ovarian cancer. Metformin is FDA approved and commercially available to treat diabetes. The combination of everolimus, metformin, and letrozole in this study to treat endometrial cancer is investigational.

Up to 64 patients will be enrolled in this study. Up to 59 may take part at MD Anderson. Up to 5 patients per site may be enrolled at MD Anderson Cooper and Spartanburg Regional Healthcare System and Harris Health System.

Keywords
Endometrial cancer, Advanced or Recurrent Endometrial Carcinoma, Metformin, Letrozole, Femara, Everolimus, Afinitor, Zortress, RAD001
Medical subject headings
Endometrial Neoplasms

What participants receive

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

  • MetforminDrug

    500 mg by mouth daily for 4 days on Days 1 - 4 of Cycle 0 and then 2 times a day (about 12 hours apart) every day after that. Metformin taken for 7 - 10 days in Cycle 0 before Cycle 1 begins.

  • LetrozoleDrug

    Also called Femara

    2.5 mg tablet by mouth once daily in a 28 day cycle.

  • EverolimusDrug

    Also called Afinitor, Zortress, RAD001

    10 mg by mouth once daily in a 28 day cycle.

Study groups in NCT01797523
Study groupRoleWhat they receive
Letrozole + Metformin + RAD001ExperimentalPatients have a 7-10 day lead in period where they take Metformin alone. The starting dose of Metformin 500 mg by mouth daily for 4 days and then increased to 500 mg by mouth twice a day. Everolimus and Letrozole added and considered the start of Cycle #1. Everolimus administered by mouth as once daily dose of 10 mg. Letrozole 2.5 mg tablet by mouth once daily. The oral dose of Everolimus should be taken together with the daily dose of Letrozole 2.5mg.
Receives: Drug: Metformin; Drug: Letrozole; Drug: Everolimus

What is being measured

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

  1. Clinical Benefit (CBR) Complete Response + Partial Response + Stable Disease Rates) Based on RECIST v1.1.

    The proportion of patients demonstrating a clinical benefit (CBR) complete response + partial response + stable disease rates) based on RECIST v1.1.

    Measured: 93 months

Secondary outcomes (3)

  1. Progression-Free Survival (PFS)

    Measured: 93 months

  2. Percentage of Participants With Toxicities Associated With RAD001, Letrozole, and Metformin

    To determine the frequency and severity of toxicities associated with RAD001, letrozole, and metformin in this cohort of patients.

    Measured: 93 months

  3. Number of Mutations Detected in Women With Endometrial Cancer

    Measured: 93 months

Timeline

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

  1. First posted22 Feb 2013 (estimated)
  2. Study start7 Oct 2013
  3. Primary completion4 Feb 2026
  4. Study completion4 Feb 2026

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
62 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01797523
Sponsor's protocol ID
2012-0543
Other IDs
NCI-2013-00960
Status last verified
Jul 2026
First submitted
20 Feb 2013
Last updated
30 Jul 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Metformin, Letrozole and Everolimus in people with Endometrial Cancer, run by M.D. Anderson Cancer Center at 6 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 12 inclusion and 18 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: finished, as of the sponsor's last update on 30 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 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?

Yes. Results are posted in the registry (first posted 30 Jul 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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 (CBR) Complete Response + Partial Response + Stable Disease Rates) Based on RECIST v1.1. (time frame: 93 months). 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 NCT01797523.

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 30 Jul 2026.

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