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

NCIC Clinical Trials Group

Status and phase

Completed

Phase 2

Conditions

Endometrial Cancer

Treatments

Other: immunohistochemistry staining method

Other: laboratory biomarker analysis

Genetic: gene expression analysis

Drug: ridaforolimus

Study type

Interventional

Funder types

NETWORK

Industry

Identifiers

NCT00770185

ARIAD-CAN-NCIC-IND192 (Other Identifier)

CAN-NCIC-IND192 (Registry Identifier)

CDR0000614597 (Other Identifier)

I192

Details and patient eligibility

About

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.

Full 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.

Enrollment

35 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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