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

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ClinicalTrials.gov Identifier: NCT00770185
Recruitment Status : Completed
First Posted : October 9, 2008
Last Update Posted : November 28, 2016
Sponsor:
Information provided by (Responsible Party):
Canadian Cancer Trials Group ( NCIC Clinical Trials Group )

Tracking Information
First Submitted Date  ICMJE October 8, 2008
First Posted Date  ICMJE October 9, 2008
Last Update Posted Date November 28, 2016
Study Start Date  ICMJE August 2008
Actual Primary Completion Date March 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 27, 2011)
  • Objective response measured by RECIST criteria [ Time Frame: every 8 weeks ]
    After every second cycle
  • Adverse events [ Time Frame: 4 years ]
    Adverse events will be monitored and assessed from the time of the first dose with overall results being assessed at final analysis.
  • Time to progression [ Time Frame: 4 years ]
  • Correlation between objective tumor response with PTEN expression and other potential markers [ Time Frame: 4 years ]
    will be assessed overall at the time of completion of therapy and final analysis.
Original Primary Outcome Measures  ICMJE
 (submitted: October 8, 2008)
  • Objective response measured by RECIST criteria
  • Adverse events
  • Time to progression
  • Correlation between objective tumor response with PTEN expression and other potential markers
Change History Complete list of historical versions of study NCT00770185 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 27, 2011)
Response duration [ Time Frame: 4 years ]
After progression with overall results assessed at final analysis
Original Secondary Outcome Measures  ICMJE
 (submitted: October 8, 2008)
Response duration
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ridaforolimus in Treating Patients With Recurrent Metastatic and/or Locally Advanced Endometrial Cancer
Official Title  ICMJE A Phase II Study of Ridaforolimus in Patients With Metastatic And/Or Locally Advanced Recurrent Endometrial Cancer
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.

Detailed Description

OBJECTIVES:

  • 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Endometrial Cancer
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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)
Interventions:
  • Drug: ridaforolimus
  • Genetic: gene expression analysis
  • Other: immunohistochemistry staining method
  • Other: laboratory biomarker analysis
Publications * Tsoref D, Welch S, Lau S, Biagi J, Tonkin K, Martin LA, Ellard S, Ghatage P, Elit L, Mackay HJ, Allo G, Tsao MS, Kamel-Reid S, Eisenhauer EA, Oza AM. Phase II study of oral ridaforolimus in women with recurrent or metastatic endometrial cancer. Gynecol Oncol. 2014 Nov;135(2):184-9. doi: 10.1016/j.ygyno.2014.06.033. Epub 2014 Aug 28.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 20, 2013)
35
Original Estimated Enrollment  ICMJE
 (submitted: October 8, 2008)
30
Actual Study Completion Date  ICMJE February 2015
Actual Primary Completion Date March 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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

PRIOR CONCURRENT THERAPY:

  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00770185
Other Study ID Numbers  ICMJE I192
CAN-NCIC-IND192 ( Registry Identifier: NCI US - Physician Data Query )
ARIAD-CAN-NCIC-IND192
CDR0000614597 ( Other Identifier: PDQ )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Canadian Cancer Trials Group ( NCIC Clinical Trials Group )
Study Sponsor  ICMJE NCIC Clinical Trials Group
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Amit M. Oza, MD Princess Margaret Hospital, Canada
PRS Account Canadian Cancer Trials Group
Verification Date February 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP