Carboplatin, Everolimus, and Prednisone in Treating Patients With Metastatic Prostate Cancer That Progressed After Docetaxel
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|ClinicalTrials.gov Identifier: NCT01051570|
Recruitment Status : Completed
First Posted : January 18, 2010
Results First Posted : August 25, 2014
Last Update Posted : December 1, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Prostate Cancer||Drug: carboplatin Drug: RAD 001 Drug: prednisone Other: laboratory biomarker analysis Other: pharmacological study||Phase 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||26 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Trial of Carboplatin and Everolimus (RAD001) in Metastatic Castrate Resistant Prostate Cancer (CRPC) Pretreated With Docetaxel Chemotherapy.|
|Study Start Date :||February 2010|
|Actual Primary Completion Date :||September 2013|
|Actual Study Completion Date :||September 2013|
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
5 mg orally twice a day starting on Day 1 then continuous
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
- 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. ]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.
- Number of Participants With Toxicity as Measured by NCI CTCAE v3.0 Criteria [ Time Frame: Day 1 of each cycle (every 21 days), through study completion, an average of 6 months ]Number of Participants with Grade 3/4 Toxicity as measured by NCI CTCAE v3.0 criteria
- PSA Response Rate [ Time Frame: Day 1 of each cycle (every 21 days), through study completion, an average of 6 months ]PSA response rate with response defined as => a 30% reduction in PSA
- Association of 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 ]PSA response defined as a decrease of 30% or more will be tabled against mTOR, pAKT, and p70S6 (1+, 2+, 3+ vs ND)
- Pharmacokinetics: Observed Carboplatin AUC Was Estimated Based on the Concentration in the 2.75-h Sample. [ Time Frame: Samples were collected Cycle 2, Day 1 ]Using a limited sampling model (i.e., AUC = 0.52 × C2.75h + 0.92) (Sorensen et al., 1993), observed carboplatin AUC was estimated based on the concentration in the 2.75-h sample.
- Overall Survival [ Time Frame: After treatment, participants will be contacted every 3 months up to 4 years ]Overall Survival as measured by the Kaplan-Meier method
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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|