Carboplatin, Everolimus, and Prednisone in Treating Patients With Metastatic Prostate Cancer That Progressed After Docetaxel
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.
Drug: RAD 001
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Trial of Carboplatin and Everolimus (RAD001) in Metastatic Castrate Resistant Prostate Cancer (CRPC) Pretreated With Docetaxel Chemotherapy.|
- Time to Progression (TTP) [ Time Frame: Up to 63 days while on treatment, then up 90 days thereafter. From date of registration to date of progressive disease. ] [ Designated as safety issue: No ]Progression defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
- Toxicity as Measured by NCI CTCAE v3.0 Criteria [ Time Frame: Day 1 of each cycle (every 21 days) ] [ Designated as safety issue: Yes ]
- PSA Response Rate [ Time Frame: Day 1 of each cycle (every 21 days) ] [ Designated as safety issue: No ]
- Association of TTP and PSA Response Rate With Correlative Markers (Phospho mTOR, pAKT, and p70S6) [ Time Frame: Archival tissue will be collected if available. Optional biopsies pre-treatment and 24 hours after first everolimus and carboplatin dose ] [ Designated as safety issue: No ]
- Pharmacokinetics [ Time Frame: Samples will be collected Cycle 1, day 1, 2 & 8 and Cycle 2, Day 1 & 2 ] [ Designated as safety issue: No ]
- Overall Survival [ Time Frame: After treatment, participants will be contacted every 3 months ] [ Designated as safety issue: No ]
|Study Start Date:||February 2010|
|Study Completion Date:||September 2013|
|Primary Completion Date:||September 2013 (Final data collection date for primary outcome measure)|
Experimental: Carboplatin, RAD 001 & Prednisone
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
AUC = 5 by Calvert's formula, day 1 of each 21 day cycle
Other Name: Paraplatin®Drug: RAD 001
5 mg orally starting on Day 2 then continuous
Other Names:Drug: prednisone
5 mg orally twice a day starting on Day 1 then continuous
Other Names:Other: laboratory biomarker analysis
Samples will be collected from archival tissue.Other: pharmacological study
Samples will be collected Cycle 1, day 1, 2 & 8 and Cycle 2, Day 1 & 2
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01051570
|United States, Illinois|
|Northshore University Health System|
|Evanston, Illinois, United States, 60201|
|United States, Michigan|
|Barbara Ann Karmanos Cancer Institute|
|Detroit, Michigan, United States, 48201-1379|
|Weisberg Cancer Treatment Center|
|Farmington Hills, Michigan, United States, 48334|
|United States, New Jersey|
|Cancer Institute of New Jersey|
|New Brunswick, New Jersey, United States, 08903|
|Principal Investigator:||Ulka N. Vaishampayan, M.D.||Barbara Ann Karmanos Cancer Institute|