A randomized phase II trial of deforolimus (AP23573; MK-8669) compared to progestin in female adult patients with advanced endometrial carcinoma following one line of chemotherapy - AP23573-07-205

• Conditions: Advanced endometrial carcinoma; MedDRA version: 9.1Level: LLTClassification code 10006869Term: Ca endometrium

• Registration Number: EUCTR2008-000634-53-IT
• Lead Sponsor: ARIAD PHARMACEUTICALS,INC.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-04-16
• Last Update Posted: 16 October 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 150

Inclusion Criteria

Eligible patients will have the following characteristics: 1. Major equal to 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 one cytotoxic regimen either: 1. As first line therapy for recurrent or metastatic disease, with documented disease progression after treatment, or 2. As adjuvant therapy, in which case the patient must have documented disease recurrence <6 months after the end of therapy. 5. The patient must have at least one measurable lesion that: Can be accurately measured in at least one dimension with longest diameter Major equal to 20 mm using conventional techniques or Major equal to 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 minor equal to 1. 7. Minimum life expectancy of 3 months. 8. Adequate renal and hepatic function, defined as: Total serum bilirubin minor equal to institutional ULN unless patient has Gilbert?s syndrome in which case direct bilirubin must be minor equal to ULN for the institution. AST and/or ALT minor equal to 2.5 x ULN for the institution. (or minor equal to 5 x ULN if liver metastases are present) Alkaline phosphatase minor equal to 1.5 x ULN for the institution (if major of 1.5 x ULN, then alkaline phosphatase liver fraction must be minor equal to 1.5 ULN). Serum creatinine minor equal to 1.5 x ULN for the institution (or calculated creatinine clearance major equal to 50 mL/min/1.73 m2) 9. Adequate bone marrow function, defined as: Total leukocytes major equal to 3.0 x 109/L. ANC major equal to 1.5 x 109/L. Platelet count major equal to 100 x 109/L. 10. Serum cholesterol minor of 350 mg/dL and triglycerides minor of 400 mg/dL. 11. Able to understand and give written informed consent. 12. Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment and must use an approved contraceptive method as appropriate from time of study screening until 30 days after the last dose of study drug. Non hormonal methods must be used. Approved contraceptive methods, intra-uterine device, diaphragm with spermicide, cervical cap with spermicide or female condom with spermicide. (Spermicides alone are not an acceptable method of contraception.) .
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

The following exclusion criteria will apply: 1. More than one prior regimen of cytotoxic chemotherapy. 2. Prior therapy with hormonal agents for endometrial cancer. 3. Women who are pregnant or lactating. 4. Presence of brain or other central nervous system metastases. 5. Prior therapy with rapamycin, rapamycin analogues or tacrolimus or known sensitivity to these agents 6. Anticancer treatment (chemotherapy, radiotherapy) within 4 weeks prior to randomization. The interval must be major equal to 6 weeks for prior nitrosourea or mitomycin therapy. 7. Ongoing toxicity associated with prior anticancer therapy (except peripheral neuropathy of minor equal to grade 1 by NCI toxicity criteria). 8. 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. 9. Another primary malignancy within the past five years (except for non-melanoma skin cancer and cervical carcinoma in situ). 10. Known Grade 3 or 4 hypersensitivity to macrolide antibiotics (e.g., clarithromycin, erythromycin, azithromycin). 11. Significant uncontrolled cardiovascular disease including NYHA class III-IV heart failure, unstable angina, or a myocardial infarction within the last six months. 12. Active infection requiring systemic therapy. 13. Known HIV infection. 14. Known hepatitis B or C infection. 15. Newly diagnosed (within 3 months before enrollment) or poorly controlled Type 1 or 2 diabetes. 16. Concurrent treatment with immunosuppressive agents . 17. Patient has a requirement for concurrent treatment with medication that strongly induce or inhibit cytochrome P450 (CYP3A). Patients should be off these medications major equal to 2 weeks prior to the first dose of deforolimus. 18. 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare progression-free survival (PFS) of patients with advanced, recurrent or metastatic endometrial cancer who have received one prior chemotherapy regimen for advanced disease when treated with deforolimus or progestin.;Secondary Objective: To compare the proportion of patients receiving deforolimus versus progestin 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 deforolimus versus progestin. To compare the best response rate of patients receiving deforolimus versus progestin. To assess the safety and tolerability of oral deforolimus in this patient population.;Primary end point(s): 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)