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Advanced, Persistent, or Recurrent Endometrial CancerPhase 2NCT02228681

Everolimus and Letrozole or Hormonal Therapy to Treat Endometrial Cancer

A Phase 2 study testing Everolimus, Tamoxifen and Letrozole in people with Advanced, Persistent, or Recurrent Endometrial Cancer, run by GOG Foundation at 26 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 main purpose of this study is to evaluate the effectiveness of the combination of the drugs Everolimus and Letrozole compared to Tamoxifen and Medroxyprogesterone acetate in treating endometrial cancer and to determine the types and severity of side effects caused by treatment with these drug combinations. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Everolimus, Tamoxifen and Letrozole
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
74 participants
Where
26 sitesUnited States
Study dates
21 May 2015to 22 Aug 2024
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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have histologically confirmed advanced (FIGO Stage III or IV), persistent, or recurrent endometrial carcinoma, which is not likely to be curable by surgery or radiotherapy. Histologic documentation of the recurrence is not required.
  • All patients must have measurable disease. Measurable disease is defined by RECIST version 1.1). Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be greater than or equal to 10 mm when measured by CT, MRI or caliper measurement by clinical exam; or greater than or equal to 20 mm when measured by chest x-ray. Lymph nodes must be greater than or equal to 15 mm in short axis when measured by CT or MRI (See section 8).
  • Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1 (Section 8.1). Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
  • Prior chemoradiotherapy for a pelvic recurrence is permitted. Prior chemotherapy in the adjuvant setting for Stage I, II or III disease is permitted.
  • Note: No prior chemotherapy in the setting of Stage IV disease is permitted unless the patient was without evidence of disease at the completion of chemotherapy and had at least six months of progression-free survival since the completion of chemotherapy.
  • Regardless of circumstances, no more than one prior chemotherapy regimen (including chemo-radiotherapy) is permitted.
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  • Patient must be able to take p.o. medications.
  • Performance status must be 0-1.
  • Patients must have adequate organ and marrow function as defined below:
  • NOTE: Institutional/laboratory upper limit of normal = ULN Institutional/laboratory lower limit of normal = LLN
  • Bone marrow function:
  • Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl
  • Platelets greater than or equal to 100,000 cells/mcl
  • Hemoglobin greater than or equal to 9 g/dL
  • Coagulation
  • INR less than or equal to 1.5 x ULN (or in range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin).
  • Renal function:
  • Creatinine less than or equal to 1.5 x ULN
  • Hepatic function:
  • Bilirubin less than or equal to 1.5 x ULN
  • ALT and AST less than or equal to 3 x ULN
  • Alkaline phosphatase less than or equal to 2.5 x ULN
  • Albumin greater than or equal to 2.8 g/dL
  • Lipid panel:
  • Fasting serum cholesterol less than or equal to 300 mg/dL
  • Fasting triglycerides less than or equal to 300 mg/
  • At least 4 weeks must have elapsed since the patient underwent any major surgery (e.g., major: hysterectomy, resection of a lung nodule; minor: central venous access catheter placement).
  • At least 4 weeks must have elapsed since the patient received any radiation therapy.
  • Patients who have met the pre-entry requirements specified in Section 7.0
  • Patients must have signed an approved informed consent and authorization permitting release of personal health information.
  • All patients must be at least 18 years of age
  • Patients of childbearing potential must have a negative serum pregnancy test prior to the study entry and be practicing a highly effective form of contraception.
  • During the study treatment and for 8 weeks after stopping the treatment. Highly effective contraception methods include combination of any two of the following:
  • Use of oral, injected or implanted hormonal methods of contraception or;
  • Placement of an intrauterine device (IUD) or intrauterine system (IUS);
  • Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository;
  • Total abstinence or;
  • Male/female sterilization. Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to randomization. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child-bearing potential.

Who cannot join

  • Patients who have previously received everolimus, any another mTOR inhibitor or any agent targeting the PI3K/AKT/mTOR pathway.
  • Known intolerance or hypersensitivity to Everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus)
  • Patients who have previously received hormonal therapy for endometrial cancer.
  • Patients with concomitant invasive malignancy or a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the past five years. Patients are also excluded if their previous cancer treatment contraindicates this protocol.
  • Patients receiving chronic treatment with systemic steroids or another immunosuppressive agent.
  • Patients with active or uncontrolled systemic infection.
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  • Uncontrolled diabetes mellitus as defined by HbA1c >8% despite adequate therapy. Patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and anti-diabetic treatment must be monitored closely throughout the trial and adjusted as necessary.
  • Known severely impaired lung function, including:
  • CTCAE grade 2 (or greater) hypoxia (decreased oxygen saturation with exercise [e.g., pulse oximeter <88%]; intermittent supplemental oxygen)
  • Patients with a known history of cardiac disease. This includes:
  • Uncontrolled hypertension, defined as systolic greater than 150 mm Hg or diastolic greater than 90 mm Hg despite antihypertensive medications.
  • Myocardial infarction or unstable angina within 6 months prior to registration.
  • New York Heart Association (NYHA) Class II or greater congestive heart failure.
  • History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or serious cardiac arrhythmia requiring medication. This does not include asymptomatic atrial fibrillation with controlled ventricular rate.
  • Cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) within 6 months prior to the first date of study therapy.
  • Patients who are pregnant or breast-feeding.
  • Patients with known central nervous system metastases.
  • Patients with known human immunodeficiency virus (HIV) infection.
  • Patients with an impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease; uncontrolled nausea, vomiting and/or diarrhea; malabsorption syndrome; clinical signs and symptoms of gastrointestinal obstruction; and/or patients who require parenteral hydration and/or nutrition).
  • Patients who plan to receive live attenuated vaccines within 1 week of start of everolimus and during the study. Patient should also avoid close contact with others who have received live attenuated vaccines. Examples of live attenuated vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and TY21a typhoid vaccines.
  • Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder or coagulopathy.
  • Patients who are currently part of or have participated in any clinical investigation with an investigational drug within 30 days prior to dosing.
  • Patients must be able to follow concomitant medication restrictions:
  • Avoid the use of strong CYP3A/PgP inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole).
  • Use caution when co-administered with moderate CYP3A4/PgP inhibitors (e.g., amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem).
  • Grapefruit, grapefruit juice, and other foods known to inhibit cytochrome P450 and PgP activity may increase everolimus exposures and should be avoided during treatment.
  • Avoid the use of concomitant strong CYP3A4/PgP inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, and phenobarbital).
  • St. John's Wort may decrease everolimus exposure unpredictably and should be avoided.
  • Patients with active hepatitis B or C. Screening for hepatitis B
  • Prior to randomization/start of everolimus, the following three categories of patients should be tested for hepatitis B viral load and serologic markers, that is, HBsAg, HBcAb, HBsAb and quantitative hepatitis B DNA PCR (HBV-DNA):
  • All patients who currently live in (or have lived in) Asia, Africa, Central and South America, Eastern Europe, Spain, Portugal and Greece.
  • [http://wwwnc.cdc.gov/travel/yellowbook/2012/chapter-3-infectious-diseases-related-to-travel/hepatitis-b.htm]
  • Patients with any of the following risk factors:
  • known or suspected past hepatitis B infection,
  • blood transfusion(s) prior to 1990,
  • current or prior IV drug users,
  • current or prior dialysis,
  • household contact with hepatitis B infected patient(s),
  • current or prior high-risk sexual activity,
  • body piercing or tattoos,
  • mother known to have hepatitis B
  • history suggestive of hepatitis B infection, e.g., dark urine, jaundice, right upper quadrant pain.
  • Additional patients at the discretion of the investigator The management guidelines, in Section 6, are provided according to the results of the baseline assessment of viral load and serological markers for hepatitis B.
  • Screening for hepatitis C
  • Patients with any of the following risk factors for hepatitis C should be tested using quantitative RNA-PCR:
  • known or suspected past hepatitis C infection (including patients with past interferon 'curative' treatment),
  • blood transfusions prior to 1990,
  • current or prior IV drug users,
  • current or prior dialysis,
  • household contact of hepatitis C infected patient(s),
  • current or prior high-risk sexual activity,
  • body piercing or tattoos. At the discretion of the investigator, additional patients may also be tested for hepatitis C.
  • The management guidelines, in Section 6 are provided according to the results of the baseline assessment of hepatitis C viral load.

Trial locations and contacts

26 sites in 1 country.

26 sites in 1 country

United States26 sites

  • Abington Memorial Hospital

    Abington, Pennsylvania, 19001-3788

  • Women's Cancer Care Associates

    Albany, New York, 12208

  • New Mexico Cancer Alliance

    Albuquerque, New Mexico, 87106

  • Memorial Medical Center-Cancer Center

    Albuquerque, New Mexico, 87131

  • University of Colorado - Anschutz Cancer Pavilion

    Aurora, Colorado, 80045

  • Johns Hopkins

    Baltimore, Maryland, 21287

  • Sanford Clinic North - Bemidji

    Bemidji, Minnesota, 56601

  • SUNY Downstate Medical Center

    Brooklyn, New York, 11203

  • University Hospital Case Medical Center

    Cleveland, Ohio, 44106

  • John B. Amos Cancer Center

    Columbus, Georgia, 31904

  • Ohio State University

    Columbus, Ohio, 43210

  • Sanford Roger Maris Cancer Center

    Fargo, North Dakota, 58122

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • St. Dominic-Jackson Memorial Hospital

    Jackson, Mississippi, 39215

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Women's Cancer Center of Nevada

    Las Vegas, Nevada, 89169

  • University of Miami - Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

  • University of Oklahoma

    Oklahoma City, Oklahoma, 73104

  • The University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Magee Women's Hospital of UPMC

    Pittsburgh, Pennsylvania, 15213

  • Women & Infants Hospital of Rhode Island

    Providence, Rhode Island, 02905

  • Huntsman Cancer Institute

    Salt Lake City, Utah, 84112

  • Memorial Health University Medical Center

    Savannah, Georgia, 31404

  • Maine Medical Center

    Scarborough, Maine, 04074

  • Sanford Medical Center - Sioux Falls

    Sioux Falls, South Dakota, 57104

  • University of Massachusetts Memorial Center

    Worcester, Massachusetts, 01605

Other trials in United States

About this study

Official title: A Randomized Phase II Trial of Everolimus and Letrozole or Hormonal Therapy (Tamoxifen/Medroxyprogesterone Acetate) in Women With Advanced, Recurrent, or Persistent Endometria Carcinoma

The main purpose of this study is to evaluate the effectiveness of the combination of the drugs Everolimus and Letrozole compared to Tamoxifen and Medroxyprogesterone acetate in treating endometrial cancer and to determine the types and severity of side effects caused by treatment with these drug combinations.

Being tested
Everolimus, Tamoxifen, Letrozole, Medroxyprogesterone Acetate

What participants receive

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

  • EverolimusDrug

    Also called RAD001

    10mg daily by mouth

  • TamoxifenDrug

    Also called Nolvadex®

    20 mg daily by mouth on alternating weeks (even numbered) weeks

  • LetrozoleDrug

    Also called Femara®

    2.5mg once a day by mouth

  • Medroxyprogesterone AcetateDrug

    200 mg daily by mouth

Study groups in NCT02228681
Study groupRoleWhat they receive
Everolimus and LetrozoleExperimentalEverolimus 10 mg daily and Letrozole 2.5 mg PO daily
Receives: Drug: Everolimus; Drug: Letrozole
Hormonal TherapyActive comparatorTamoxifen 20 mg PO BID; on alternating weeks (even numbered) weeks, Medroxyprogesterone Acetate 200 mg PO daily with Tamoxifen 20 mg PO BID
Receives: Drug: Tamoxifen; Drug: Medroxyprogesterone Acetate

What is being measured

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

  1. Frequency of Response

    A confirmed complete or partial response as defined by RECIST 1.1 was considered a response. "Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

    Measured: From date of randomization until the date of first documented progression or date of death , up to 3 years.

Secondary outcomes (3)

  1. Median Progression-free Survival

    Progression-free Survival is defined as the duration alive from study entry until progression is documented, or death; whichever comes sooner. Progressive disease is defined as at least a 5 mm absolute increase and a 20% relative increase in the sum of measurable target lesions' longest dimensions relative to the smallest sum at baseline or on study or the appearance of new lesions or unequivocal progression of existing non-target lesions.

    Measured: Tumor measurements were done at 8 and 16 weeks after initiating treatment and then every 12 weeks and compared with baseline measurements prior to treatment. Measurements are continued until disease progression is documented or death.

  2. Frequency and Severity of CTCAE (Common Toxicity Criteria for Adverse Events) Version 4

    Maximum grade of physician assessed adverse events graded and categorized using Common Toxicity Criteria for Adverse Events (CTCAE) version 4

    Measured: Assessed throughout the treatment period and for 30 days after discontinuation of treatment. Treatment continues until progression of disease.

  3. Median Survival

    Survival is defined as the duration alive from study entry until death.

    Measured: Following treatment discontinuation, patients are followed quarterly for 2 years, semi-annually for 3 more years, annually thereafter.

Timeline

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

  1. First posted29 Aug 2014 (estimated)
  2. Study start21 May 2015
  3. Primary completionJan 2018
  4. Study completion22 Aug 2024

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
74 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02228681
Sponsor's protocol ID
GOG-3007
Other IDs
CRAD001CUS236T
Status last verified
Aug 2024
First submitted
14 Aug 2014
Last updated
19 Sep 2024
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Everolimus, Tamoxifen and Letrozole in people with Advanced, Persistent, or Recurrent Endometrial Cancer, run by GOG Foundation at 26 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 38 inclusion and 53 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 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 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 24 May 2019). 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?

Frequency of Response (time frame: From date of randomization until the date of first documented progression or date of death , up to 3 years.). 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 NCT02228681.

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 19 Sep 2024.

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