Clinical Trials/NCT02228681

NCT02228681

Active, not recruiting

Phase 2

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

GOG Foundation26 sites in 1 country74 target enrollmentMay 21, 2015

ConditionsAdvanced, Persistent, or Recurrent Endometrial Cancer

InterventionsEverolimus Letrozole Tamoxifen Medroxyprogesterone Acetate

DrugsEverolimus Tamoxifen Letrozole Medroxyprogesterone Acetate

Overview

Phase: Phase 2
Intervention: Everolimus
Conditions: Advanced, Persistent, or Recurrent Endometrial Cancer
Sponsor: GOG Foundation
Enrollment: 74
Locations: 26
Primary Endpoint: Frequency of Response
Status: Active, not recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

May 21, 2015

End Date

January 2018

Last Updated

2 years ago

Study Type

Interventional

Study Design

Parallel

Sex

Female

Investigators

Sponsor

GOG Foundation

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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-
•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

Exclusion Criteria

•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:

Arms & Interventions

Everolimus and Letrozole

Everolimus 10 mg daily and Letrozole 2.5 mg PO daily

Intervention: Everolimus

Everolimus and Letrozole

Everolimus 10 mg daily and Letrozole 2.5 mg PO daily

Intervention: Letrozole

Hormonal Therapy

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

Intervention: Tamoxifen

Hormonal Therapy

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

Intervention: Medroxyprogesterone Acetate

Outcomes

Primary Outcomes

Frequency of Response

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

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

Secondary Outcomes

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