Impact of Temsirolimus Therapy on Circulating Tumor Cell Biology In Men With Castration Resistant Metastatic Prostate Cancer
This study has been terminated.
National Comprehensive Cancer Network
Information provided by (Responsible Party):
First received: April 23, 2009
Last updated: January 23, 2013
Last verified: January 2013
This is a single arm study of 20 men with treatment refractory metastatic CRPC who will receive temsirolimus IV at a dose of 25 mg weekly until progression. Progression will not include 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.
||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||Impact of Temsirolimus Therapy on Circulating Tumor Cell Biology In Men With Castration Resistant Metastatic Prostate Cancer
Primary Outcome Measures:
- To evaluate change in circulating tumor cell (CTC) counts over time in men with metastatic treatment-refractory castration-resistant prostate cancer. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- To evaluate the change in CTC counts upon the addition of an anti-androgen upon PSA progression while on temsirolimus therapy [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- To evaluate the changes in measures of epithelial plasticity on CTCs in response to mTOR inhibition with temsirolimus, using genomic and protein immunohistochemical methodology. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- To evaluate and correlate changes in serum LDH with CTC count changes over time in men with CRPC treated with temsirolimus. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||August 2012 (Final data collection date for primary outcome measure)
dosage form: IV dosage, frequency and duration: 25mg weekly until clinical progression
Other Name: Torisel
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Histologically confirmed carcinoma of the prostate. Histologic evidence may be confirmed through local or metastatic biopsy review
- Radiographic Evidence of metastatic disease
- Evidence of disease progression despite castrate levels of testosterone.
- A circulating timor cell count using FDA approved CellSearch methodology of ≥ 10 per 7.5 cc whole blood, drawn within 4 weeks of study registration
- Serum PSA greater than or equal to 2ng/dl at registration
- At least 4 weeks since prior palliative radiation therapy and/or major surgery, and resolution of all toxic effects of prior therapy NCI CTCAE Grade less than or equal to 1
- Age ≥ 18 years
- Adequate laboratory parameters
- Karnofsy Performance Status ≥ 60
- Life expectancy of at least 3 months
- History of or active central nervous system metastases
- The use of cytotoxic, biologic, or hormonal therapies within 4 weeks of study entry.
- Subjects receiving known strong CYP3A4 isoenzyme inhibitors and/or inducers
- Major surgery, open biopsy, traumatic injury, or radiotherapy within 4 weeks of the screening visit
- Have not recovered from prior biopsy, surgery, traumatic injury, and/or radiation therapy.
- Presence of non-healing wound or ucer
- Grade ≥ 3 hemorrhage in the past month to study entry
- Hypertension with systolic blood pressure of ≥ 180mmHg and/or diastolic pressure ≥ 100mmHg (Anti-hypertensive medications are permitted)
- Subjects with Class 2-4 heart disease or any history of congestive heart failure with an ejection fraction <50% or a recent (within 12 months) cardiovascular event.
- Anticoagulation with warfarin
- Diabetes mellitus with glycosylated hemoglobin A1c ≥ 10% despite therapy
- History of interstitial pneumonitis
- Subjects with active autoimmune disorder(s) being treated with immunosuppressive agents within 4 weeks prior to screening visit
- Subjects receiving immunosuppressive agents and those with chronic viral/bacterial/fungal illnesses. Replacement doses of corticosteroids are permitted.
- Active infection(s), active antimicrobial therapy or serious intercurrent illness.
- History of other prior malignancy in past 5 years, other than basal cell carcinoma, squamous cell carcinoma of the skin, cervical carcinoma in sity, localized prostate cancer, or superficial bladder cancer.
- Agreement to use medically acceptable contraceptive methods while on study and for 3 months after the last dose of temsirolimus.
- Any other major medical or psychiatric illness that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in this study, including inability to absorb oral medications.
- Known hypersensitivity to any of the components in the temsirolimus infusion or other medical reasons for not being able to receive adequate premedication.
- QTc interval on baseline EKG of >500 milliseconds
- the use of agents that significantly prolong the QTc interval and who are unable to stop medications prior to study initiation.
- Prior exposure to an mTOR inhibitor
- Presence of nephrotic syndrome as determined by clinical evaluation of 24 hour urine.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00887640
|Duke University Medical Center
|Durham, North Carolina, United States, 27710 |
|Virginia Oncology Associates
|Norfolk, Virginia, United States, 23502 |
National Comprehensive Cancer Network
||Andrew Armstrong, MD, ScM
||Duke Unversity Medical Center
No publications provided
History of Changes
|Other Study ID Numbers:
|Study First Received:
||April 23, 2009
||January 23, 2013
||United States: Institutional Review Board
Keywords provided by Duke University:
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on December 08, 2013
Neoplastic Cells, Circulating
Genital Neoplasms, Male
Neoplasms by Site
Genital Diseases, Male
Physiological Effects of Drugs