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

Sponsor

NCIC Clinical Trials Group (Other)

Overall Status

Completed

CT.gov ID

NCT00770185

Collaborator

Ariad Pharmaceuticals (Industry)

Enrollment

Locations

Arm

77.6

Actual Duration (Months)

3.2

Patients Per Site

Patients Per Site Per Month

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

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 Design

Study Type:

Interventional

Actual Enrollment :

35 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

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

Objective response measured by RECIST criteria [every 8 weeks]
After every second cycle
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.
Time to progression [4 years]
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

Response duration [4 years]
After progression with overall results assessed at final analysis

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

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