Everolimus First-line Therapy in Non-rapidly Progressive Castration Resistant Prostate Cancer (CRPC). A Multicenter Phase II Trial.
Everolimus First-line Therapy in Non-rapidly Progressive Castration Resistant Prostate Cancer (CRPC). A Multicenter Phase II Trial.
RATIONALE: Everolimus 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 everolimus and to see how well it works as first-line therapy in treating patients with prostate cancer.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter study.
Patients receive oral everolimus once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed up at 28 days and then every 3 months.
DISEASE CHARACTERISTICS:
Histologically confirmed metastatic or locally advanced adenocarcinoma of the prostate
Tumor progression after ≥ 1 hormonal treatment (orchiectomy or luteinizing-hormone releasing-hormone [LHRH] agonist) with documented total testosterone levels ≤ 1.7 nmol/L (≤ 50 ng/dL)
PSA progression defined as an increase in PSA ≥ 25% (and an absolute increase of 2 ng/mL or more) over nadir value on hormonal therapy measured on 3 successive occasions ≥ 1 week apart
No known or suspected CNS metastases
PATIENT CHARACTERISTICS:
WHO performance status 0-1
ANC ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥ 90 g/L
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
AST ≤ 2.5 times ULN
Creatinine clearance ≥ 40 mL/min
Fasting serum cholesterol ≤ 7.75 mmol/L AND fasting triglycerides ≤ 2.5 times ULN
Patient compliance and geographic proximity that would allow proper staging and follow-up are required
No malignancy within the past 5 years except curatively treated localized nonmelanoma skin cancer or Ta and Tis bladder cancer
No known history of HIV
No serologically confirmed hepatitis B or C
No serious underlying medical condition that, in the judgment of the investigator, could impair the ability of the patient to participate in the trial including, but not limited to, any of the following conditions:
No psychiatric disorder precluding understanding of information on trial-related topics, giving informed consent, or interfering with compliance for oral drug intake
No known hypersensitivity to trial drug or hypersensitivity to any of its components
PRIOR CONCURRENT THERAPY:
See Disease Characteristics
No prior chemotherapy, radioisotopes, small molecules, immunotherapy, or investigational drug therapy for prostate cancer
No local radiotherapy within the past 2 weeks
No major surgery within the past 4 weeks
No concurrent radiotherapy
No concurrent angiotensin converting enzyme inhibitors
No concurrent chronic immunosuppressive therapy including high-dose corticosteroids (i.e., > 25 mg prednisone equivalent per day)
No products known to affect PSA levels (e.g., PC Calm, PC Plus, PC SPES, finasteride, or fluconazole) within the past 4 weeks or concurrently
No strong CYP3A4 inhibitors (e.g., itraconazole, erythromycin, clarithromycin, diltiazem, verapamil, or grapefruit or its juice) within the past 2 weeks or concurrently
No strong CYP3A4 inducers (e.g., phenytoin, rifampicin, carbamazepine, phenobarbital, or St. John wort) within the past 2 weeks or concurrently
No concurrent bisphosphonates
No concurrent experimental drugs or other anticancer therapy in a clinical trial within the past 30 days
No concomitant drugs contraindicated for use with the trial drug according to the investigator's drug brochure