Everolimus and Letrozole or Hormonal Therapy to Treat Endometrial Cancer

NCT02228681 | Completed Phase 2 Results

• 2 other identifiers: GOG-3007CRAD001CUS236T
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 26

Brief 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.

Conditions

Advanced, Persistent, or Recurrent Endometrial Cancer

Outcome Measures

Primary Outcomes (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

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

Secondary Outcomes (3)

• Median Progression-free Survival

  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.

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

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

• Median Survival

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

Other Outcomes (3)

• Hormone Receptor Immunohistochemistry

  At study entry

• mTOR Pathway Immunohistochemistry

  At study entry

• Mutation Analysis

  At study entry

Study Arms (2)

Everolimus and Letrozole

EXPERIMENTAL

Everolimus 10 mg daily and Letrozole 2.5 mg PO daily

Drug: Everolimus; Drug: Letrozole

Hormonal Therapy

ACTIVE COMPARATOR

Tamoxifen 20 mg PO BID; on alternating weeks (even numbered) weeks, Medroxyprogesterone Acetate 200 mg PO daily with Tamoxifen 20 mg PO BID

Drug: Tamoxifen; Drug: Medroxyprogesterone Acetate

Interventions

Everolimus DRUG

10mg daily by mouth

Also known as: RAD001

Everolimus and Letrozole

Tamoxifen DRUG

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

Also known as: Nolvadex®

Hormonal Therapy

Letrozole DRUG

2.5mg once a day by mouth

Also known as: Femara®

Everolimus and Letrozole

Medroxyprogesterone Acetate DRUG

200 mg daily by mouth

Hormonal Therapy

Eligibility Criteria

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

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

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.

Sponsors & Collaborators

• GOG Foundation: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (26)

University of Colorado - Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

Location

University of Miami - Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

John B. Amos Cancer Center

Columbus, Georgia, 31904, United States

Location

Memorial Health University Medical Center

Savannah, Georgia, 31404, United States

Location

Maine Medical Center

Scarborough, Maine, 04074, United States

Location

Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

University of Massachusetts Memorial Center

Worcester, Massachusetts, 01605, United States

Location

Sanford Clinic North - Bemidji

Bemidji, Minnesota, 56601, United States

Location

St. Dominic-Jackson Memorial Hospital

Jackson, Mississippi, 39215, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Women's Cancer Center of Nevada

Las Vegas, Nevada, 89169, United States

Location

New Mexico Cancer Alliance

Albuquerque, New Mexico, 87106, United States

Location

Memorial Medical Center-Cancer Center

Albuquerque, New Mexico, 87131, United States

Location

Women's Cancer Care Associates

Albany, New York, 12208, United States

Location

SUNY Downstate Medical Center

Brooklyn, New York, 11203, United States

Location

Sanford Roger Maris Cancer Center

Fargo, North Dakota, 58122, United States

Location

University Hospital Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

Location

Abington Memorial Hospital

Abington, Pennsylvania, 19001-3788, United States

Location

The University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Magee Women's Hospital of UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

Women & Infants Hospital of Rhode Island

Providence, Rhode Island, 02905, United States

Location

Sanford Medical Center - Sioux Falls

Sioux Falls, South Dakota, 57104, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Interventions

Everolimus; Tamoxifen; Letrozole; Medroxyprogesterone Acetate

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Medroxyprogesterone; Hydroxyprogesterones; Progesterone; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Linda Gedeon for Virginia Filiaci, PhD
• Organization: GOG Foundation

lgedeon@gogstats.org

716-845-1169

Study Officials

• Brian Slomovitz, MD

  Gynecologic Oncology Group

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: August 14, 2014
• First Posted: August 29, 2014
• Study Start: May 21, 2015
• Primary Completion: January 1, 2018
• Study Completion: August 22, 2024
• Last Updated: September 19, 2024
• Results First Posted: May 24, 2019

Record last verified: 2024-08

Locations

US (26)