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

Endometrial Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00739830
• Other study ID #: 8669-007
• Secondary ID: AP23573-07-205
• Status: Completed
• Phase: Phase 2
• First received: August 20, 2008
• Last updated: June 30, 2015
• Start date: August 2008
• Est. completion date: July 2012

Study information

• Verified date: June 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 130
• Est. completion date: July 2012
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Endometrial Cancer
• Endometrial Neoplasms

Intervention

Drug:
• ridaforolimus
40 mg once daily oral tablets for 5 days followed by 2 days without ridaforolimus
• 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)
• 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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS)		From randomization up to 30 months	No
Secondary	The proportion of patients progression free at 16 weeks as assessed using modified RECIST guidelines.		From randomization to Week 16	No
Secondary	The proportion of patients progression free at 26 weeks as assessed using modified RECIST guidelines		From randomization to Week 26	No
Secondary	Overall survival		From randomization up to 30 months	No
Secondary	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	No
Secondary	Safety and tolerability		From randomization up to 30 days after discontinuation of treatment	Yes