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

Endometrial Cancer Clinical Trial

Official title:

A Phase II Study of Ridaforolimus in Patients With Metastatic And/Or Locally Advanced Recurrent Endometrial Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00770185
• Other study ID #: I192
• Secondary ID: CAN-NCIC-IND192A
• Status: Completed
• Phase: Phase 2
• Start date: November 13, 2008
• Est. completion date: February 13, 2015

Study information

• Verified date: April 2020
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: February 13, 2015
• Est. primary completion date: March 19, 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Endometrial Cancer
• Endometrial Neoplasms

Intervention

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

• laboratory biomarker analysis

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	BCCA - Cancer Centre for the Southern Interior	Kelowna	British Columbia
Canada	Cancer Centre of Southeastern Ontario at Kingston	Kingston	Ontario
Canada	London Regional Cancer Program	London	Ontario
Canada	CHUM - Hopital Notre-Dame	Montreal	Quebec
Canada	McGill University - Dept. Oncology	Montreal	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	BCCA - Fraser Valley Cancer Centre	Surrey	British Columbia
Canada	Univ. Health Network-Princess Margaret Hospital	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
NCIC Clinical Trials Group	Ariad Pharmaceuticals

Country where clinical trial is conducted

Canada, 

References & Publications (1)

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 On — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response measured by RECIST criteria	After every second cycle	every 8 weeks
Primary	Adverse events	Adverse events will be monitored and assessed from the time of the first dose with overall results being assessed at final analysis.	4 years
Primary	Time to progression		4 years
Primary	Correlation between objective tumor response with PTEN expression and other potential markers	will be assessed overall at the time of completion of therapy and final analysis.	4 years
Secondary	Response duration	After progression with overall results assessed at final analysis	4 years