Clinical Trial of Ridaforolimus Compared to Progestin or Chemotherapy for Advanced Endometrial Carcinoma (MK-8669-007 AM6)

Study Overview
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Brief Summary
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The purpose of this study is 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, and then when treated with ridaforolimus or the investigators' choice of progestin or chemotherapy.

Official Title
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A Randomized Phase II Trial of Ridaforolimus (AP23573; MK-8669) Compared to Progestin or Chemotherapy in Female Adult Patients With Advanced Endometrial Carcinoma

Conditions
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Endometrial Cancer

Intervention / Treatment
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* Drug: ridaforolimus
* Drug: medroxyprogesterone acetate tablets OR megestrol acetate
* Drug: chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older Endometrial cancer Patients must have been treated with at least one line of chemotherapy, but not more than two lines of chemotherapy, and experienced progressive disease At least one measurable lesion ECOG performance status less than or equal to 1 Minimum life expectancy of 3 months Adequate renal and hepatic function Adequate bone marrow function Serum cholesterol <350 mg/dL and triglycerides < 400 mg/dL Able to understand and give written informed consent Females of childbearing potential must have a negative pregnancy test and use approved contraception from screening to 30 days after the last study drug is given Exclusion Criteria: Two lines of chemotherapy for recurrent or metastatic disease Chemotherapy for recurrent or metastatic disease administered within six months of adjuvant therapy More than two lines of chemotherapy of any type Prior therapy with hormonal agents Women who are pregnant or lactating Presence of brain or other central nervous system metastases Prior therapy with rapamycin, rapamycin analogues or tacrolimus or known sensitivity to these agents Anticancer treatment (chemotherapy, radiotherapy) within 4 weeks prior to randomization Ongoing toxicity associated with prior anticancer therapy Inadequate recovery from any prior surgical procedure or having undergone any major surgical procedure within 2 weeks prior to randomization. Another primary malignancy within the past five years (except for non-melanoma skin cancer and cervical carcinoma in situ) Known Grade 3 or 4 hypersensitivity to macrolide antibiotics Significant uncontrolled cardiovascular disease Active infection Known HIV infection Known Hepatitis B or C infection Newly diagnosed (within 3 months before enrollment) or poorly controlled Type 1 or 2 diabetes Concurrent treatment with immunosuppressive agents A requirement for concurrent treatment with medication that strongly induce or inhibit cytochrome P450 (CYP3A)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>40 mg once daily oral tablets for 5 days followed by 2 days without ridaforolimus | Drug: ridaforolimus<br>* 40 mg once daily oral tablets for 5 days followed by 2 days without ridaforolimus<br>* Other names: deforolimus, AP23573, MK-8669; ridaforolimus was also known as deforolimus until May 2009;|
| Active Comparator: 2<br>Investigator's choice of: oral medroxyprogesterone acetate tablets 200 mg daily or oral megestrol acetate tablets 40 mg 4 times per day (160 mg daily) OR Chemotherapy - carboplatin, paclitaxel, doxorubicin, pegylated liposomal doxorubicin or topotecan administered as a single agent or as a doublet, and will be administered at doses and schedules chosen by the investigator | Drug: medroxyprogesterone acetate tablets OR megestrol acetate<br>* oral medroxyprogesterone acetate tablets 200 mg daily OR oral megestrol acetate tablets 40 mg 4 times per day (160 mg daily)<br>Drug: chemotherapy<br>* Chemotherapy - carboplatin, paclitaxel, doxorubicin, pegylated liposomal doxorubicin or topotecan administered as a single agent or as a doublet, and will be administered at doses and schedules chosen by the investigator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) |  | From randomization up to 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients progression free at 16 weeks as assessed using modified RECIST guidelines. |  | From randomization to Week 16 | 
| The proportion of patients progression free at 26 weeks as assessed using modified RECIST guidelines |  | From randomization to Week 26 | 
| Overall survival |  | From randomization up to 30 months | 
| Best target lesion response, defined as best change in sum of the target lesions from baseline to disease progression |  | From randomization up to 30 months | 
| Safety and tolerability |  | From randomization up to 30 days after discontinuation of treatment |