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

Sponsor

Merck Sharp & Dohme LLC (Industry)

Overall Status

Completed

CT.gov ID

NCT00739830

Collaborator

(none)

130

Enrollment

Arms

Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Endometrial Cancer	Drug: ridaforolimus Drug: medroxyprogesterone acetate tablets OR megestrol acetate Drug: chemotherapy	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

130 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Aug 1, 2008

Actual Primary Completion Date :

Feb 1, 2011

Actual Study Completion Date :

Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 40 mg once daily oral tablets for 5 days followed by 2 days without ridaforolimus	Drug: ridaforolimus 40 mg once daily oral tablets for 5 days followed by 2 days without ridaforolimus Other Names: deforolimus, AP23573, MK-8669; ridaforolimus was also known as deforolimus until May 2009
Active Comparator: 2 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 oral medroxyprogesterone acetate tablets 200 mg daily OR oral megestrol acetate tablets 40 mg 4 times per day (160 mg daily) Drug: chemotherapy 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

Arm

Intervention/Treatment

Experimental: 1

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

Drug: ridaforolimus

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

Other Names:

deforolimus, AP23573, MK-8669; ridaforolimus was also known as deforolimus until May 2009

Active Comparator: 2

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

oral medroxyprogesterone acetate tablets 200 mg daily OR oral megestrol acetate tablets 40 mg 4 times per day (160 mg daily)

Drug: chemotherapy

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

Outcome Measures

Primary Outcome Measures

Progression-free survival (PFS) [From randomization up to 30 months]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts 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)