Everolimus and Letrozole or Hormonal Therapy to Treat Endometrial Cancer

Completed · Phase 2

Conditions studied: Advanced, Persistent, or Recurrent Endometrial Cancer

In brief

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.

Key facts

Study ID

NCT02228681

Run by

GOG Foundation

People needed

74

Starts

2015-05-21

Expected to finish

2024-08-22

Last updated by the study team

2024-09-19

Who can join

Age: 18 and older. Sex: female. Healthy volunteers: not accepted.

You may qualify if…

• 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.
• 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

You may not qualify if…

• 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.
• 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).

Where it is running

• University of Colorado - Anschutz Cancer Pavilion — Aurora, Colorado, United States
• University of Miami - Sylvester Comprehensive Cancer Center — Miami, Florida, United States
• John B. Amos Cancer Center — Columbus, Georgia, United States
• Memorial Health University Medical Center — Savannah, Georgia, United States
• Maine Medical Center — Scarborough, Maine, United States
• Johns Hopkins — Baltimore, Maryland, United States
• University of Massachusetts Memorial Center — Worcester, Massachusetts, United States
• Sanford Clinic North - Bemidji — Bemidji, Minnesota, United States
• St. Dominic-Jackson Memorial Hospital — Jackson, Mississippi, United States
• University of Mississippi Medical Center — Jackson, Mississippi, United States
• Women's Cancer Center of Nevada — Las Vegas, Nevada, United States
• New Mexico Cancer Alliance — Albuquerque, New Mexico, United States
• Memorial Medical Center-Cancer Center — Albuquerque, New Mexico, United States
• Women's Cancer Care Associates — Albany, New York, United States
• SUNY Downstate Medical Center — Brooklyn, New York, United States
• Sanford Roger Maris Cancer Center — Fargo, North Dakota, United States
• University Hospital Case Medical Center — Cleveland, Ohio, United States
• Ohio State University — Columbus, Ohio, United States
• University of Oklahoma — Oklahoma City, Oklahoma, United States
• Abington Memorial Hospital — Abington, Pennsylvania, United States
• The University of Pennsylvania — Philadelphia, Pennsylvania, United States
• Magee Women's Hospital of UPMC — Pittsburgh, Pennsylvania, United States
• Women & Infants Hospital of Rhode Island — Providence, Rhode Island, United States
• Sanford Medical Center - Sioux Falls — Sioux Falls, South Dakota, United States
• University of Texas MD Anderson Cancer Center — Houston, Texas, United States

Full record on ClinicalTrials.gov

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