Clinical trial NCT00887640: Impact of Temsirolimus Therapy on Circulating Tumor Cell Biology In Men With Castration Resistant Metastatic Prostate Cancer
Official title: Impact of Temsirolimus Therapy on Circulating Tumor Cell Biology In Men With Castration Resistant Metastatic Prostate Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: metastatic
Temsirolimus
prostate
cancer
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Comprehensive Cancer Network
First posted: 2009-04-24
Enrollment: 11
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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 Common Toxicity Criteria for Adverse Effects (CTCAE) Grade less than or equal to 1
* Age ≥ 18 years
* Adequate laboratory parameters
* Karnofsky Performance Status ≥ 60
* Life expectancy of at least 3 months

Exclusion Criteria:

* 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 Cytochrome P450 3A4 (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 ≥ 180 mmHg and/or diastolic pressure ≥ 100 mmHg (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.
* Corrected QT interval on baseline EKG of \>500 milliseconds
* the use of agents that significantly prolong the Corrected QT interval and who are unable to stop medications prior to study initiation.
* Prior exposure to an Mammalian Target of Rapamycin (mTOR) inhibitor
* Presence of nephrotic syndrome as determined by clinical evaluation of 24 hour urine.

Primary outcomes:
measure: Change in Circulating Tumor Cell (CTC) Counts in Men With Metastatic Treatment-refractory Castration-resistant Prostate Cancer.
timeFrame: Baseline to 8 weeks
Secondary outcomes:
measure: Percent Change in CTC Count From Baseline to 12 Weeks of Treatment.
timeFrame: Baseline to 12 weeks
measure: Mean Percent of N-cadherin Expression at Baseline and 8 Weeks of Treatment.
timeFrame: Baseline and 8 weeks
measure: Percent Change in LDH
timeFrame: Baseline to 12 weeks
measure: Median Progression-Free Survival (PFS)
timeFrame: 2 years
measure: Maximum Rate of Change of Prostate-Specific Antigen (PSA).
timeFrame: Baseline to 7 months
measure: Time to PSA Progression
timeFrame: 2 years
measure: Time to Second PSA Progression After Addition of Anti-androgen Therapy
timeFrame: 2 years
measure: Change Over Time in CTC Gene Expression Profile
timeFrame: 12 weeks
measure: Safety and Tolerability of Temsirolimus
timeFrame: 2 years
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
Study officials:
affiliation: Duke Unversity Medical Center
name: Andrew Armstrong, MD, ScM
role: PRINCIPAL_INVESTIGATOR
References: