Everolimus as First-Line Therapy in Treating Patients With Prostate Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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OBJECTIVES: Primary Determine the progression-free survival at 12 weeks of patients with non-rapidly progressive castration-resistant prostate cancer treated with everolimus as first-line therapy. Assess the activity and safety of this regimen in these patients. Secondary Determine the progression-free survival at 24 weeks of patients treated with this regimen. Determine the percentage of PSA response from baseline to 12 weeks in patients treated with this regimen. Determine the changes in PSA-doubling time in patients treated with this regimen. Determine the overall survival of patients treated with this regimen. 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.

Official Title
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Everolimus First-line Therapy in Non-rapidly Progressive Castration Resistant Prostate Cancer (CRPC). A Multicenter Phase II Trial.

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: everolimus


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed metastatic or locally advanced adenocarcinoma of the prostate No curative therapy available Oligosymptomatic or asymptomatic patients 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) Concurrent LHRH agonist therapy is required for patients who have not been surgically castrated Must have stopped antiandrogen therapy ≥ 6 weeks before the start of trial treatment without withdrawal response 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 If the third measurement is not higher than the second, a fourth measurement will be taken (patient allowed if the fourth measurement is higher than the second) PSA doubling time ≥ 55 days 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 Appropriate lipid-lowering medication allowed in case one or both of these thresholds are exceeded 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: Uncontrolled or acute severe infection Uncontrolled diabetes Advanced chronic obstructive pulmonary disease 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 Patients must continue to receive bisphosphonates regularly if it was started prior to entering the trial 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Everolimus<br>Everolimus: 10mg daily | Drug: everolimus<br>* Everolimus: 10mg daily<br>* Other names: RAD001;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) at 12 weeks | PFS at 12 weeks is defined as the absence of disease progression or death at 12 weeks after start of treatment. | at 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS at 24 weeks | PFS at 24 weeks is defined as the absence of any disease progression or death at 24 weeks after start of treatment. | at 24 weeks | 
| Progression-free survival | from start of treatment until progression or death of any cause, whereas it will be censored at the last follow-up visit or initiation of a different treatment. | from start of treatment until progression or death of any cause | 
| Adverse events (AEs) according to NCI CTCAE v. 3.0 | All AEs will be assessed according to NCI CTCAE v3.0 | from start of treatment until progression or death of any cause | 
| PSA response | 50% PSA response is defined as a decrease in PSA level of at least 50% (compared to baseline PSA). 30% PSA response is defined as a decrease in PSA level of at least 30% (compared to baseline PSA). Best response is defined as the percentage of change in PSA from baseline to the maximum decline in PSA at any point under treatment. Response at 12 weeks is defined as the percentage of change in PSA from baseline to 12 weeks (or earlier for those patients who discontinue therapy, in this case last PSA values recorded should be taken). | 50% and 30%, best and at 12 weeks | 
| Changes in PSA-doubling time | PSA-DT is calculated by natural log of 2 divided by the slope of the relationship between the log of PSA and time of PSA measurement for each patient. | Time points for later calculations include: after 12 weeks, after 24 weeks and at best PSA response | 
| Tumor assessment of measurable disease according to RECIST v1.1 criteria | For patients with measurable disease at baseline RECIST v1.1 will be used to define CR, PR, SD and PD. | The first assessment will be performed after 12 weeks of treatment, or earlier if clinically indicated. | 
| Tumor assessment of bone lesions | Bone metastases can be assessed by radionuclide bone scan. | at 12 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the prostate, hormone-resistant prostate cancer, stage III prostate cancer, stage IV prostate cancer