Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Symptoms and General Pathology

Prostatic Neoplasms

Neoplastic Cells, Circulating

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Neoplasm Metastasis

Neoplastic Processes

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Anti-Allergic Agents

Antiemetics

Central Nervous System Depressants

Gastrointestinal Agents

Dermatologic Agents

Sirolimus

Histamine Antagonists

Histamine H1 Antagonists

Diphenhydramine

Promethazine

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Hypnotics and Sedatives

Anesthetics

Anesthetics, Local

Histamine

Histamine phosphate

Neurotransmitter Agents

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

Dosage form: IV or PO Dosage, frequency and duration: 25-50mg, 30 minutes prior to Temsirolimus infusion

Andrew Armstrong, MD, ScM

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.

Impact of Temsirolimus Therapy on Circulating Tumor Cell Biology In Men With Castration Resistant Metastatic Prostate Cancer

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.

To evaluate the change in CTC counts upon the addition of an anti-androgen upon PSA progression while on temsirolimus therapy

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.

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

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.

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 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 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.

Percent change in CTC gene expression from baseline to 8 or 12 weeks of treatment.

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.

National Comprehensive Cancer Network

Duke University

The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov

Temsirolimus 25 mg

Age, Continuous

Sex: Female, Male

Dr. Andrew Armstrong

CTC count at both baseline and week 8 were assessable in 8 of the 11 patients as CTCs were collected at both time points in these patients. Missing CTC data for 3 of the 11 patients due to laboratory error or no CTC available at various time points.

Change in Circulating Tumor Cell (CTC) Counts in Men With Metastatic Treatment-refractory Castration-resistant Prostate Cancer.

Data were insufficient to evaluate this outcome. Outcome not available at 12 weeks. CTCs were not collected at week 12 and thus were not analyzed.

Percent Change in CTC Count From Baseline to 12 Weeks of Treatment.

Expression at baseline

Expression at 8 weeks

N-cadherin expression at both baseline and 8 weeks was evaluable in 7 patients.

Mean Percent of N-cadherin Expression at Baseline and 8 Weeks of Treatment.

Data were insufficient to evaluate this outcome. Data not collected. This outcome was not performed due to availability and feasibility of the tests involved.

Percent Change in LDH

Median Progression-Free Survival (PFS)

Maximum Rate of Change of Prostate-Specific Antigen (PSA).

Data were insufficient to evaluate this outcome. Data not collected. PSA responses were not observed in this study and PSA progression dates would essentially be the same as the radiographic PFS dates.

Time to PSA Progression

Data were insufficient to evaluate this outcome. Data not collected. Patients progressed radiographically before 2nd PSA progression occurred.

Spots Global Cancer Trial Database for Impact of Temsirolimus Therapy on Circulating Tumor Cell Biology In Men With Castration Resistant Metastatic Prostate Cancer

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