Impact of Temsirolimus Therapy on Circulating Tumor Cell Biology In Men With Castration Resistant Metastatic Prostate Cancer
This is a single arm study of 11 men with treatment refractory metastatic Castrate Resistant Prostate Cancer (CRPC) who will receive temsirolimus IV at a dose of 25 mg weekly until progression. Progression will not include Prostate Specific Antigen (PSA) progression; however, upon PSA progression, the addition of an anti-androgen will be permitted. The primary objective of the study is to evaluate change in circulating tumor cell (CTC) counts over time in men with metastatic treatment-refractory CRPC in response to temsirolimus therapy.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Impact of Temsirolimus Therapy on Circulating Tumor Cell Biology In Men With Castration Resistant Metastatic Prostate Cancer|
- Change in Circulating Tumor Cell (CTC) Counts in Men With Metastatic Treatment-refractory Castration-resistant Prostate Cancer. [ Time Frame: Baseline to 8 weeks ] [ Designated as safety issue: No ]Median percent change in CTC count from baseline to 8 weeks of treatment. Percent change was calculated by determining the percentage increase or decrease in CTC count from baseline.
- Percent Change in CTC Count From Baseline to 12 Weeks of Treatment. [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]To evaluate the change in CTC counts upon the addition of an anti-androgen upon PSA progression while on temsirolimus therapy
- Mean Percent of N-cadherin Expression at Baseline and 8 Weeks of Treatment. [ Time Frame: Baseline and 8 weeks ] [ Designated as safety issue: No ]Measures of epithelial plasticity on CTCs in response to Mammalian Target of Rapamycin (mTOR) inhibition with temsirolimus, using genomic and protein immunohistochemical methodology. N-cadherin was measured in CTCs captured using the CellSearch profile kit. The proportion of CTCs expressing N-cadherin was calculated and divided by the total number of CD45-negative, pan cytokeratin (CK) - positive, and 4',6-diamidino-2-phenylindole (DAPI+) intact cells to give a fractional expression of N-cadherin. Results are reported as a percentage.
- Percent Change in LDH [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]To evaluate and correlate changes in serum Lactate Dehydrogenase (LDH) with CTC count changes over time in men with Castrate Resistant Prostate Cancer (CRPC) treated with temsirolimus
- Median Progression-Free Survival (PFS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]Time in months from the start of study treatment to the date of first progression according to Prostate Cancer Clinical Trial Working Group 2 (PCWG2) criteria, or to death due to any cause. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Additionally, according to PCWG2 criteria, disease progression in bone is defined as 2 or more new lesions seen on bone scan compared with the baseline scan used for trial entry. Per PCWG2 guidelines, therapy was not discontinued solely due to a rise in PSA alone.
- Maximum Rate of Change of Prostate-Specific Antigen (PSA). [ Time Frame: Baseline to 7 months ] [ Designated as safety issue: No ]Percent change in PSA between baseline and the measurement time point where the largest change in PSA occurred. Note that a positive change (greater than 0) indicates an increase in PSA, and a negative change (less than 0) indicates a decrease.
- Time to PSA Progression [ Time Frame: 2 years ] [ Designated as safety issue: No ]Time in months from the start of study treatment to the date of first PSA progression . Patients alive who had not progressed as of the last follow-up or patients who had expired had time to PSA progression censored at the last follow-up date or death date. The median was estimated using a Kaplan-Meier curve.
- Time to Second PSA Progression After Addition of Anti-androgen Therapy [ Time Frame: 2 years ] [ Designated as safety issue: No ]Time in months from the time of anti-androgen therapy to the date of second PSA progression . Patients alive who had not progressed as of the last follow-up or patients who had expired had time to second PSA progression censored at the last follow-up date or death date. The median was estimated using a Kaplan-Meier curve.
- Change Over Time in CTC Gene Expression Profile [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]Percent change in CTC gene expression from baseline to 8 or 12 weeks of treatment.
- Safety and Tolerability of Temsirolimus [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]Total number of grade 3, 4, and 5 adverse events at least possibly related to temsirolimus therapy. Adverse events were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 and were converted to 4.0 for the purposes of reporting to ClinicalTrials.gov.
|Study Start Date:||July 2009|
|Study Completion Date:||August 2012|
|Primary Completion Date:||August 2012 (Final data collection date for primary outcome measure)|
Experimental: Temsirolimus 25 mg
Temsirolimus 25mg was administered by IV infusion each week (days 1, 8, 15, and 22 of each 28 day cycle). The infusion was to be administered over a period not less than 30 minutes and was to be completed within 60 minutes. Subjects were premedicated with 25 to 50 mg IV or PO diphenhydramine (or an alternative antihistamine in case of allergies) 30 minutes prior to the infusion.
dosage form: IV dosage, frequency and duration: 25mg weekly until clinical progression
Other Name: ToriselDrug: Diphenhydramine
Dosage form: IV or PO Dosage, frequency and duration: 25-50mg, 30 minutes prior to Temsirolimus infusion
Other Name: Benadryl
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|United States, Virginia|
|Virginia Oncology Associates|
|Norfolk, Virginia, United States, 23502|
|Principal Investigator:||Andrew Armstrong, MD, ScM||Duke Unversity Medical Center|