Clinical trial NCT00770185: Ridaforolimus in Treating Patients With Recurrent Metastatic and/or Locally Advanced Endometrial Cancer
Official title: A Phase II Study of Ridaforolimus in Patients With Metastatic And/Or Locally Advanced Recurrent Endometrial Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Endometrial Cancer
Keywords: endometrial adenocarcinoma
endometrial adenosquamous cell carcinoma
endometrial clear cell carcinoma
endometrial papillary carcinoma
recurrent endometrial carcinoma
stage III endometrial carcinoma
stage IV endometrial carcinoma
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
Collaborators: name: Ariad Pharmaceuticals
First posted: 2008-10-09
Enrollment: 35
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Objective response measured by RECIST criteria
timeFrame: every 8 weeks
measure: Adverse events
timeFrame: 4 years
measure: Time to progression
timeFrame: 4 years
measure: Correlation between objective tumor response with PTEN expression and other potential markers
timeFrame: 4 years
Secondary outcomes:
measure: Response duration
timeFrame: 4 years
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Kelowna
country: Canada
facility: BCCA - Cancer Centre for the Southern Interior
state: British Columbia
city: Surrey
country: Canada
facility: BCCA - Fraser Valley Cancer Centre
state: British Columbia
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre at Hamilton Health Sciences
state: Ontario
city: Kingston
country: Canada
facility: Cancer Centre of Southeastern Ontario at Kingston
state: Ontario
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Toronto
country: Canada
facility: Univ. Health Network-Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: CHUM - Hopital Notre-Dame
state: Quebec
city: Montreal
country: Canada
facility: McGill University - Dept. Oncology
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
Study officials:
affiliation: Princess Margaret Hospital, Canada
name: Amit M. Oza, MD
role: STUDY_CHAIR
References:
citation: 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.