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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00739830
First received: August 20, 2008
Last updated: August 9, 2012
Last verified: August 2012
  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:


Further study details as provided by Merck Sharp & Dohme Corp.:

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

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
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
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Diseases
Genital Diseases, Female
Liposomal doxorubicin
Doxorubicin
Sirolimus
Medroxyprogesterone Acetate
Megestrol
Megestrol Acetate
Medroxyprogesterone
Progestins
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014