advanced endometrial carcinoma MedDRA version: 14.1 Level: LLT Classification code 10014747 Term: Endometrial carcinoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.1 Level: LLT Classification code 10014745 Term: Endometrial carcinoma metastatic System O
Conditions
Sponsors
Merck Sharp & Dohme Corp.,
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.=18 years of age. 2.Patients must have unresectable stage III or IVa, or metastatic (stage IVb), or recurrent histologically-confirmed endometrial cancer. 3.Endometrial cancer will include all carcinomas, including endometrioid carcinoma, papillary serous carcinoma, clear cell carcinoma, and carcinosarcomas. Leiomyosarcomas are not included. 4.Patients must have been treated with at least one line of chemotherapy, but not more than two and experienced progressive disease. Adjuvant therapy may be allowed as is up to one line of chemotherapy for recurrent or metastatic disease. These criteria are described in detail in Table 11.1.4-1. 5.The patient must have at least one measurable lesion that: •Can be accurately measured in at least one dimension with longest diameter = 20 mm using conventional techniques or =10 mm with spiral CT scan (or otherwise at least twice the reconstruction interval for CT or MRI scans). •Previously irradiated lesions may be considered to be measurable provided: 1) there has been documented progression of the lesion(s) since completion of radiotherapy, and 2) the criteria for measurability as outlined above are met. 6.ECOG performance status = 1. 7.Minimum life expectancy of 3 months. 8.Adequate renal and hepatic function, defined as: •Total serum bilirubin = institutional ULN unless patient has Gilbert’s syndrome in which case direct bilirubin must be =ULN for the institution. •AST and/or ALT = 2.5 x ULN for the institution. (or = 5 x ULN if liver metastases are present) •Alkaline phosphatase =1.5 x ULN for the institution (if > 1.5 x ULN, then alkaline phosphatase liver fraction must be =1.5 ULN). •Serum creatinine = 1.5 x ULN for the institution (or calculated creatinine clearance = 50 mL/min/1.73 m2) 9.Adequate bone marrow function, defined as: •Total leukocytes = 3.0 x 109/L. •ANC = 1.5 x 109/L. •Platelet count = 100 x 109/L. 10.Serum cholesterol =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Two lines of chemotherapy for recurrent or metastatic disease. 2. Chemotherapy for recurrent or metastatic disease administered within six months of adjuvant therapy. 3. more than two lines of chemotherapy of any type. 4.Prior therapy with hormonal agents for endometrial cancer. 5..Women who are pregnant or lactating. 6.Presence of brain or other central nervous system metastases. 7.Prior therapy with rapamycin, rapamycin analogues or tacrolimus or known sensitivity to these agents. 8.Anticancer treatment (chemotherapy, radiotherapy) within 4 weeks prior to randomization. The interval must be = 6 weeks for prior nitrosourea or mitomycin therapy. 9.Ongoing toxicity associated with prior anticancer therapy (except peripheral neuropathy of = grade 1 by NCI toxicity criteria). 10.Inadequate recovery from any prior surgical procedure or having undergone any major surgical procedure within 2 weeks prior to randomization. Patients who have recovered from placement of a central venous access port within 2 weeks of Cycle 1 Day 1 will be considered eligible. 11.Another primary malignancy within the past five years (except for non-melanoma skin cancer and cervical carcinoma in situ). 12.Known Grade 3 or 4 hypersensitivity to macrolide antibiotics (e.g., clarithromycin, erythromycin, azithromycin). 13.Significant uncontrolled cardiovascular disease including NYHA class III-IV heart failure, unstable angina, or a myocardial infarction within the last six months. 14.Active infection requiring systemic therapy. 15.Known HIV infection. 16.Known hepatitis B or C infection. 17.Newly diagnosed (within 3 months before enrollment) or poorly controlled Type 1 or 2 diabetes. 18.Concurrent treatment with immunosuppressive agents. 19.Patient has a requirement for concurrent treatment with medications that strongly induce or inhibit cytochrome P450 (CYP3A). Patients should be off these medications = 2 weeks prior to the first dose of ridaforolimus. 20.Presence of any other life-threatening illness or organ system dysfunction which, in the opinion of the Investigator, would either compromise the patient’s safety or interfere with evaluating the safety of the study drug.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare progression-free survival (PFS) of patients with advanced, recurrent or metastatic endometrial cancer who have received one, but not more than two prior lines of chemotherapy either as adjuvant therapy or treatment for advanced disease as defined in Table 11.1.4-1. and then treated with ridaforolimus or the investigator's choice of progestin or chemotherapy.; Secondary Objective: •To compare the proportion of patients receiving ridaforolimus versus the investigators' choice of progestin or chemotherapy who are progression-free at 16 weeks and 26 weeks post randomization as assessed using modified RECIST guidelines. •To compare the overall survival (OS) of patients receiving ridaforolimus versus the investigators' choice of progestin or chemotherapy. •To compare the best response rate of patients receiving ridaforolimus versus progestin or chemotherapy. •To assess the safety and tolerability of oral ridaforolimus in this patient population. Exploratory Objective: •To assess changes in Quality of Life parameters in those patients treated with ridaforolimus compared to those treated with the investigators' choice of progestin or chemotherapy. ;Primary end point(s): The primary endpoint is progression-free survival, defined as the time from the date of randomization to the date of documented progressive disease, recurrence or death (whichever occurs first). | — |
Countries
Czech Republic, France, Germany, Italy, Spain, United Kingdom
Outcome results
None listed