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

Purpose

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	Intervention	Phase
Endometrial Cancer	Drug: ridaforolimus Drug: medroxyprogesterone acetate tablets OR megestrol acetate Drug: chemotherapy	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Benign Tumors Cancer

Drug Information available for: Medroxyprogesterone acetate Megestrol acetate Doxorubicin Doxorubicin hydrochloride

U.S. FDA Resources

Further study details as provided by Merck:

Primary Outcome Measures:

Progression-free survival (PFS) [ Time Frame: From randomization up to 30 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

The proportion of patients progression free at 16 weeks as assessed using modified RECIST guidelines. [ Time Frame: From randomization to Week 16 ] [ Designated as safety issue: No ]
The proportion of patients progression free at 26 weeks as assessed using modified RECIST guidelines [ Time Frame: From randomization to Week 26 ] [ Designated as safety issue: No ]
Overall survival [ Time Frame: From randomization up to 30 months ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Safety and tolerability [ Time Frame: From randomization up to 30 days after discontinuation of treatment ] [ Designated as safety issue: Yes ]

Enrollment:	130
Study Start Date:	August 2008
Study Completion Date:	July 2012
Primary Completion Date:	February 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 Name: 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

Arms

Assigned Interventions

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 Name: 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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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)

Contacts and Locations

No Contacts or Locations Provided

More Information

No publications provided

Responsible Party:	Merck
ClinicalTrials.gov Identifier:	NCT00739830 History of Changes
Other Study ID Numbers:	MK-8669-007, AP23573-07-205
Study First Received:	August 20, 2008
Last Updated:	August 9, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Endometrial Neoplasms
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Carcinoma
Uterine Diseases
Genital Diseases, Female
Doxorubicin
Sirolimus
Medroxyprogesterone Acetate

Megestrol
Megestrol Acetate
Medroxyprogesterone
Progestins
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Contraceptive Agents, Male

ClinicalTrials.gov processed this record on May 16, 2013