Endometrial Cancer
Conditions
Brief summary
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.
Interventions
DRUGridaforolimus
40 mg once daily oral tablets for 5 days followed by 2 days without ridaforolimus
DRUGmedroxyprogesterone acetate tablets OR megestrol acetate
oral medroxyprogesterone acetate tablets 200 mg daily OR oral megestrol acetate tablets 40 mg 4 times per day (160 mg daily)
DRUGchemotherapy
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
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free survival (PFS) | From randomization up to 30 months |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
Outcome results
None listed