Ridaforolimus in Treating Patients With Recurrent Metastatic and/or Locally Advanced Endometrial Cancer

NCIC Clinical Trials Group (Other)
Overall Status
CT.gov ID
Ariad Pharmaceuticals (Industry)

Study Details

Study Description

Brief Summary

RATIONALE: Ridaforolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying the side effects of ridaforolimus and to see how well it works in treating patients with recurrent metastatic and/or locally advanced endometrial cancer.

Condition or Disease Intervention/Treatment Phase
  • Drug: ridaforolimus
  • Genetic: gene expression analysis
  • Other: immunohistochemistry staining method
  • Other: laboratory biomarker analysis
Phase 2

Detailed Description

  • To assess the efficacy, in terms of objective response rate, of ridaforolimus, in patients with recurrent metastatic and/or locally advanced endometrial cancer.

  • To assess the adverse events, time to progression, and response duration of this drug in these patients.

  • To correlate objective tumor response with PTEN expression and other potential markers in primary tumor tissue from these patients.

OUTLINE: This is a multicenter study.

Patients receive oral ridaforolimus once daily on days 1-5 for 4 weeks. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Archived tumor tissue samples (paraffin block or unstained slides) are analyzed for PTEN gene expression and other mTOR pathway elements to explore possible markers of response or non-progression by immunohistochemistry.

After completion of study treatment, patients are followed at 4 weeks and then every 3 months thereafter.

Study Design

Study Type:
Actual Enrollment :
35 participants
Intervention Model:
Single Group Assignment
None (Open Label)
Primary Purpose:
Official Title:
A Phase II Study of Ridaforolimus in Patients With Metastatic And/Or Locally Advanced Recurrent Endometrial Cancer
Actual Study Start Date :
Aug 26, 2008
Actual Primary Completion Date :
Mar 19, 2012
Actual Study Completion Date :
Feb 13, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: Ridaforolimus

oral ridaforolimus 40 mg days 1-5 each week (once daily for 5 consecutive days every week; cycle arbitrarily defined as a 4 week period)

Drug: ridaforolimus
oral ridaforolimus 40 mg days 1-5 each week (once daily for 5 consecutive days every week; cycle arbitrarily defined as a 4 week period)

Genetic: gene expression analysis

Other: immunohistochemistry staining method

Other: laboratory biomarker analysis

Outcome Measures

Primary Outcome Measures

  1. Objective response measured by RECIST criteria [every 8 weeks]

    After every second cycle

  2. Adverse events [4 years]

    Adverse events will be monitored and assessed from the time of the first dose with overall results being assessed at final analysis.

  3. Time to progression [4 years]

  4. Correlation between objective tumor response with PTEN expression and other potential markers [4 years]

    will be assessed overall at the time of completion of therapy and final analysis.

Secondary Outcome Measures

  1. Response duration [4 years]

    After progression with overall results assessed at final analysis

Eligibility Criteria


Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
Accepts Healthy Volunteers:
  • Histologically confirmed endometrial cancer, including any 1 of the following subtypes:

  • Adenocarcinoma

  • Papillary serous

  • Papillary

  • Villoglandular

  • Mucinous

  • Clear cell

  • Endometrioid

  • Adenosquamous carcinoma

  • Recurrent or metastatic and/or locally advanced disease

  • Incurable disease by standard therapies

  • Clinically and/or radiologically documented disease within the past 28 days (35 days if negative), defined as ≥ 1 unidimensionally measurable disease site meeting 1 of the following criteria:

  • At least 20 mm by x-ray or physical exam

  • At least 10 mm by spiral CT scan

  • At least 20 mm by non-spiral CT scan

  • Available tumor tissue (paraffin block or unstained slides) from primary tumor

  • No uterine sarcoma (leiomyosarcoma), mixed müllerian tumor (MMT), and/or adenosarcoma

  • No known brain metastases

  • Clinical suspicion of CNS involvement requires a head CT scan

  • ECOG performance status 0-2

  • Life expectancy ≥ 12 weeks

  • Granulocyte count ≥ 1,500/mm³

  • Platelet count ≥ 100,000/mm³

  • Bilirubin ≤ upper limit of normal (ULN)

  • ALT and AST ≤ 2.5 times ULN

  • Creatinine ≤ 1.25 times ULN OR creatinine clearance ≥ 50 mL/min

  • Fasting serum cholesterol ≤ 9.0 mmol/L

  • Fasting triglycerides ≤ 4.56 mmol/L

  • Not pregnant or nursing

  • Negative pregnancy test

  • Fertile patients must use effective contraception

  • Accessible for treatment and follow up (e.g., 1 ½ hours driving distance from participating center)

  • No upper gastrointestinal or other condition that would impair swallowing or absorption of oral medication

  • No serious illness or medical condition that would not permit the patient to be managed according to the protocol, including, but not limited to, any of the following:

  • History of significant neurologic or psychiatric disorder (e.g., uncontrolled psychotic disorders) that would impair the ability to obtain consent or limit compliance with study requirements

  • Active uncontrolled or serious infection

  • Active peptic ulcer disease

  • Myocardial infarction within the past 6 months, congestive heart failure (even if medically controlled), unstable angina, active cardiomyopathy, unstable ventricular arrhythmia, or uncontrolled hypertension

  • Pulmonary disease requiring oxygen

  • HIV infection or other immune deficiency

  • Other medical conditions that might be aggravated by study treatment

  • No history of other malignancies, except adequately treated nonmelanoma skin cancer, curatively treated carcinoma in situ of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years

  • No known hypersensitivity to the study drug or its components

  • At least 7 days since prior hormonal therapy (progestational or aromatase inhibitor) as either adjuvant therapy or for treatment of metastatic disease

  • At least 21 days since prior major surgery and recovered

  • At least 28 days since prior radiotherapy and recovered

  • Prior low-dose palliative radiotherapy allowed

  • At least 4 months since prior adjuvant chemotherapy

  • No prior mTOR inhibitors

  • No prior or concurrent chemotherapy for metastatic or recurrent disease

  • More than 7 days since prior and no concurrent CYP3A4 inhibitors including, but not limited to, any of the following:

  • Azole antifungals (i.e., ketoconazole, itraconazole, miconazole, fluconazole)

  • HIV protease inhibitors (i.e., indinavir, saquinavir, ritonavir, atazanavir, nelfinavir)

  • Clarithromycin

  • Verapamil

  • Erythromycin

  • Delavirdine

  • Diltiazem

  • Nefazodone

  • Telithromycin

  • More than 12 days since prior and no concurrent CYP3A4 inducers including, but not limited to, any of the following:

  • Rifampin

  • Phenytoin

  • Rifabutin

  • St. John's wort

  • Carbamazepine

  • Efavirenz

  • Phenobarbital

  • Tipranavir

  • At least 14 days since prior and no concurrent investigational drugs or anticancer therapy (e.g., immunotherapy, biological response modifiers [excluding hematopoietic growth factors], and systemic hormonal therapy)

  • No concurrent CYP3A4 substrates

Contacts and Locations


Site City State Country Postal Code
1 Tom Baker Cancer Centre Calgary Alberta Canada T2N 4N2
2 Cross Cancer Institute Edmonton Alberta Canada T6G 1Z2
3 BCCA - Cancer Centre for the Southern Interior Kelowna British Columbia Canada V1Y 5L3
4 BCCA - Fraser Valley Cancer Centre Surrey British Columbia Canada V3V 1Z2
5 Juravinski Cancer Centre at Hamilton Health Sciences Hamilton Ontario Canada L8V 5C2
6 Cancer Centre of Southeastern Ontario at Kingston Kingston Ontario Canada K7L 5P9
7 London Regional Cancer Program London Ontario Canada N6A 4L6
8 Univ. Health Network-Princess Margaret Hospital Toronto Ontario Canada M5G 2M9
9 CHUM - Hopital Notre-Dame Montreal Quebec Canada H2L 4M1
10 McGill University - Dept. Oncology Montreal Quebec Canada H2W 1S6
11 Allan Blair Cancer Centre Regina Saskatchewan Canada S4T 7T1

Sponsors and Collaborators

  • NCIC Clinical Trials Group
  • Ariad Pharmaceuticals


  • Study Chair: Amit M. Oza, MD, Princess Margaret Hospital, Canada

Study Documents (Full-Text)

None provided.

More Information


None provided.
Responsible Party:
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
Other Study ID Numbers:
  • I192
  • CDR0000614597
First Posted:
Oct 9, 2008
Last Update Posted:
Apr 8, 2020
Last Verified:
Apr 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:
Studies a U.S. FDA-regulated Drug Product:
Studies a U.S. FDA-regulated Device Product:
Keywords provided by NCIC Clinical Trials Group
Additional relevant MeSH terms:

Study Results

No Results Posted as of Apr 8, 2020