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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00770185
First received: October 8, 2008
Last updated: February 7, 2014
Last verified: February 2014
  Purpose

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 Intervention Phase
Endometrial Cancer
Drug: ridaforolimus
Genetic: gene expression analysis
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Ridaforolimus in Patients With Metastatic And/Or Locally Advanced Recurrent Endometrial Cancer

Resource links provided by NLM:


Further study details as provided by NCIC Clinical Trials Group:

Primary Outcome Measures:
  • Objective response measured by RECIST criteria [ Time Frame: every 8 weeks ] [ Designated as safety issue: No ]
    After every second cycle

  • Adverse events [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
  • Correlation between objective tumor response with PTEN expression and other potential markers [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    will be assessed overall at the time of completion of therapy and final analysis.


Secondary Outcome Measures:
  • Response duration [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    After progression with overall results assessed at final analysis


Enrollment: 35
Study Start Date: August 2008
Estimated Study Completion Date: December 2014
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

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

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
  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.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00770185

Locations
Canada, Alberta
Tom Baker Cancer Centre
Calgary, Alberta, Canada, T2N 4N2
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
BCCA - Cancer Centre for the Southern Interior
Kelowna, British Columbia, Canada, V1Y 5L3
BCCA - Fraser Valley Cancer Centre
Surrey, British Columbia, Canada, V3V 1Z2
Canada, Ontario
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8V 5C2
Cancer Centre of Southeastern Ontario at Kingston
Kingston, Ontario, Canada, K7L 5P9
London Regional Cancer Program
London, Ontario, Canada, N6A 4L6
Univ. Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
CHUM - Hopital Notre-Dame
Montreal, Quebec, Canada, H2L 4M1
McGill University - Dept. Oncology
Montreal, Quebec, Canada, H2W 1S6
Canada, Saskatchewan
Allan Blair Cancer Centre
Regina, Saskatchewan, Canada, S4T 7T1
Sponsors and Collaborators
NCIC Clinical Trials Group
Investigators
Study Chair: Amit M. Oza, MD Princess Margaret Hospital, Canada
  More Information

Additional Information:
No publications provided

Responsible Party: NCIC Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00770185     History of Changes
Other Study ID Numbers: I192, CAN-NCIC-IND192, ARIAD-CAN-NCIC-IND192, CDR0000614597
Study First Received: October 8, 2008
Last Updated: February 7, 2014
Health Authority: Canada: Health Canada

Keywords provided by NCIC Clinical Trials Group:
endometrial adenocarcinoma
endometrial adenosquamous cell carcinoma
endometrial clear cell carcinoma
endometrial papillary carcinoma
recurrent endometrial carcinoma
stage III endometrial carcinoma
stage IV endometrial carcinoma

Additional relevant MeSH terms:
Endometrial Neoplasms
Genital Diseases, Female
Genital Neoplasms, Female
Neoplasms
Neoplasms by Site
Urogenital Neoplasms
Uterine Diseases
Uterine Neoplasms
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014