The Use of RAD001 With Docetaxel in the Treatment of Metastatic, Androgen Independent Prostate Cancer
The purpose of this study is to evaluate the safety and optimal dose of RAD001 and docetaxel plus prednisone in men with hormone refractory, metastatic prostate cancer (Phase I).
Once an appropriate dose is reached, the purpose then will be to determine the response rate of docetaxel plus RAD001 (Phase II).
Metastatic, Androgen Independent Prostate Cancer
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of RAD001 With Docetaxel in the Treatment of Metastatic, Androgen Independent Prostate Cancer|
- Number of Patients Free of Dose Limiting Toxicity [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
A dose limiting toxicity was defined as an adverse event or laboratory abnormality that occurs to patients on the Phase I portion of the trial, during the first 21 days following the first dose of RAD001/docetaxel during cycle 1, judged to be related to RAD001/docetaxel and meeting any of the following criteria:
CTCAE grade 4 neutropenia > 7 days or any Grade 3 or 4 neutropenia with fever Or CTCAE grade 3 or 4 thrombocytopenia > 7 days
The occurrence of non-hematologic CTCAE grade 3 or 4 adverse events will be considered dose limiting, except for the following:
- CTCAE grade 3 nausea or grade 3 or 4 vomiting CTCAE grade 3 or 4 vomiting will only be considered dose limiting if it occurs despite the use of standard anti-emetics.
- CTCAE grade 3 or 4 fever identified with a source (i.e. infection, tumor)
- CTCAE grade 3 or 4 alkaline phosphatase.
- Response Based on PET Scan [ Time Frame: 10 to 14 days after study entry ] [ Designated as safety issue: No ]Patients were scanned using Positron Emission Tomography (PET) before and after receiving single agent RAD001. Patients were classified as having partial metabolic response, stable metabolic disease, or progressive metabolic disease based on changes in PET imaging from baseline to post-treatment. A positive FDG-PET for the purposes of this study consisted of a visualized area of abnormal increased FDG uptake that matched the anatomic location of an abnormality seen on bone scan or CT. Metabolic response was assessed for percent change in SUVmax according to the criteria of the European Organization for Research and Treatment of Cancer (EORTC) : partial metabolic response (PMR) ≤ -25%; stable metabolic disease (SMD) -25% + 25%; progressive metabolic disease (PMD) > 25%.
|Study Start Date:||November 2005|
|Study Completion Date:||December 2012|
|Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
Experimental: RAD001 Followed by RAD001 + Docetaxel
RAD001 10 mg daily for 2 weeks, followed by RAD001 + Docetaxel at one of three doses: 5 mg RAD001 and docetaxel at 60 mg/m2, 10 mg RAD001 and docetaxel at 60 mg/m2, and 10 mg RAD001 and docetaxel at 70 mg/m2. RAD001 was given daily. Docetaxel was given every 3 weeks by intravenous infusion. Patients also received prednisone 5 mg by mouth twice daily.
Daily for two weeksDrug: Docetaxel
Infusion once per cycleDrug: Prednisone
Prednisone 5 mg by mouth twice daily
- Patients will be designated into one of two groups based upon the results of a FDG-PET scan.
- A patient with a baseline positive scan will have serum drawn for baseline serum proteomics assessment then be treated with RAD001 daily for two weeks. On day 10-14, another FDG-PET scan and serum assessment will be performed. An optional bone marrow biopsy may also be done. On day 15, patients will enter the Phase I portion of the trial at the current enrolling dosage or if Phase I is completed patients will enter Phase II.
- A patient that does not have a positive scan will enter directly into the Phase I trial or Phase II depending on which trial is currently enrolling.
- Phase I trial patients will have weekly laboratory evaluations and clinical evaluation every three weeks.
- Phase II trial patients will have laboratory evaluations on day one and day eight and clinical evaluation every three weeks.
- The maximum duration of the trial is one year of therapy.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00459186
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Brigham and Women's Hospital|
|Boston, Massachusetts, United States, 02115|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|Beth Israel Deaconess Medical Center|
|Boston, Massachusetts, United States, 02215|
|United States, Oregon|
|Oregon Health Science University|
|Portland, Oregon, United States|
|Principal Investigator:||Mary Ellen Taplin, MD||Dana-Farber Cancer Institute|