Clinical Trial of Ridaforolimus Compared to Progestin or Chemotherapy for Advanced Endometrial Carcinoma (MK-8669-007 AM6)
Primary Purpose
Endometrial Cancer
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
ridaforolimus
medroxyprogesterone acetate tablets OR megestrol acetate
chemotherapy
Sponsored by
About this trial
This is an interventional treatment trial for Endometrial Cancer
Eligibility Criteria
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)
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
1
2
Arm Description
40 mg once daily oral tablets for 5 days followed by 2 days without ridaforolimus
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
Outcomes
Primary Outcome Measures
Progression-free survival (PFS)
Secondary Outcome Measures
The proportion of patients progression free at 16 weeks as assessed using modified RECIST guidelines.
The proportion of patients progression free at 26 weeks as assessed using modified RECIST guidelines
Overall survival
Best target lesion response, defined as best change in sum of the target lesions from baseline to disease progression
Safety and tolerability
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00739830
Brief Title
Clinical Trial of Ridaforolimus Compared to Progestin or Chemotherapy for Advanced Endometrial Carcinoma (MK-8669-007 AM6)
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 Type
Interventional
2. Study Status
Record Verification Date
June 2015
Overall Recruitment Status
Completed
Study Start Date
August 2008 (undefined)
Primary Completion Date
February 2011 (Actual)
Study Completion Date
July 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Endometrial Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
130 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
40 mg once daily oral tablets for 5 days followed by 2 days without ridaforolimus
Arm Title
2
Arm Type
Active Comparator
Arm 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
Intervention Type
Drug
Intervention Name(s)
ridaforolimus
Other Intervention Name(s)
deforolimus, AP23573, MK-8669; ridaforolimus was also known as deforolimus until May 2009
Intervention Description
40 mg once daily oral tablets for 5 days followed by 2 days without ridaforolimus
Intervention Type
Drug
Intervention Name(s)
medroxyprogesterone acetate tablets OR megestrol acetate
Intervention Description
oral medroxyprogesterone acetate tablets 200 mg daily OR oral megestrol acetate tablets 40 mg 4 times per day (160 mg daily)
Intervention Type
Drug
Intervention Name(s)
chemotherapy
Intervention Description
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
Primary Outcome Measure Information:
Title
Progression-free survival (PFS)
Time Frame
From randomization up to 30 months
Secondary Outcome Measure Information:
Title
The proportion of patients progression free at 16 weeks as assessed using modified RECIST guidelines.
Time Frame
From randomization to Week 16
Title
The proportion of patients progression free at 26 weeks as assessed using modified RECIST guidelines
Time Frame
From randomization to Week 26
Title
Overall survival
Time Frame
From randomization up to 30 months
Title
Best target lesion response, defined as best change in sum of the target lesions from baseline to disease progression
Time Frame
From randomization up to 30 months
Title
Safety and tolerability
Time Frame
From randomization up to 30 days after discontinuation of treatment
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
12. IPD Sharing Statement
Citations:
PubMed Identifier
26077241
Citation
Oza AM, Pignata S, Poveda A, McCormack M, Clamp A, Schwartz B, Cheng J, Li X, Campbell K, Dodion P, Haluska FG. Randomized Phase II Trial of Ridaforolimus in Advanced Endometrial Carcinoma. J Clin Oncol. 2015 Nov 1;33(31):3576-82. doi: 10.1200/JCO.2014.58.8871. Epub 2015 Jun 15.
Results Reference
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Clinical Trial of Ridaforolimus Compared to Progestin or Chemotherapy for Advanced Endometrial Carcinoma (MK-8669-007 AM6)
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