Conditions: Prostate Cancer
Keywords: hormone-resistant prostate cancer recurrent prostate cancer stage IV prostate cancer adenocarcinoma of the prostate
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 26
Healthy volunteers: no

Brief summary:
RATIONALE: Drugs used in chemotherapy, such as carboplatin and prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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. Giving carboplatin together with everolimus and prednisone may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving carboplatin together with everolimus and prednisone works in treating patients with metastatic prostate cancer that progressed after docetaxel.

Detailed description:
OBJECTIVES:

Primary

* To evaluate the time to progression (TTP) achieved with carboplatin and everolimus in patients with castrate resistant metastatic prostate cancer that progressed after docetaxel-based chemotherapy.

Secondary

* To evaluate the safety of this regimen.
* To assess the PSA response rate in patients treated with this regimen.
* To evaluate the overall survival (OS) outcome in these patients.
* To investigate the association of TTP and PSA response rate with correlative markers, such as phospho mTOR, pAKT, and p70S6.
* To evaluate the pharmacokinetics of this regimen.
* To explore the association of TTP, OS, and circulating tumor tumor cell count.

OUTLINE: Patients receive carboplatin IV over 30-60 minutes on day 1, oral prednisone twice daily on days on days 1-21, and oral everolimus once daily on days 2-21 of course 1 and on days 1-21 of subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Blood and tumor tissue samples are collected periodically for pharmacodynamic, pharmacokinetic, and biomarker analysis.

After completion of study treatment, patients are followed up every 3 months.

Arms:
arm 1: Carboplatin: AUC=4 by Calvert's formula (max dose 600 mg)\*IV over 30-60 min, Day 1 of a 21 day cycle

RAD 001: 5 mg Orally daily, starting from Day 2 continuously

Prednisone 5 mg Orally twice daily, continuously

Interventions: intervention 1: carboplatin intervention 2: RAD 001 intervention 3: prednisone intervention 4: laboratory biomarker analysis intervention 5: pharmacological study
Intervention descriptions: intervention 1: AUC = 5 by Calvert's formula, day 1 of each 21 day cycle intervention 2: 5 mg orally starting on Day 2 then continuous intervention 3: 5 mg orally twice a day starting on Day 1 then continuous intervention 4: Samples will be collected from archival tissue. intervention 5: Samples will be collected Cycle 1, day 1, 2 \& 8 and Cycle 2, Day 1 \& 2

Protocol document: