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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: Endometrial Cancer

Treatments: Drug: medroxyprogesterone acetate tablets OR megestrol acetate; Drug: chemotherapy; Drug: ridaforolimus

Study type: Interventional

Funder types: Industry

Identifiers

NCT00739830

8669-007

AP23573-07-205 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 130 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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130 participants in 2 patient groups

1

Experimental group

Description:

40 mg once daily oral tablets for 5 days followed by 2 days without ridaforolimus

Treatment:

Drug: ridaforolimus

2

Active Comparator group

Description:

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

Treatment:

Drug: chemotherapy

Drug: medroxyprogesterone acetate tablets OR megestrol acetate