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

• Status: Completed
• Trial end date: 2015-02-13
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: NCIC Clinical Trials Group
• Collaborator: Ariad Pharmaceuticals
• Treatments: Sirolimus

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