Prostate CancerPhase 2NCT00887640
Impact of Temsirolimus Therapy on Circulating Tumor Cell Biology In Men With Castration Resistant Metastatic Prostate Cancer
A Phase 2 study testing Temsirolimus and Diphenhydramine in people with Prostate Cancer, run by Duke University at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Temsirolimus and Diphenhydramine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 2 sitesUnited States
- Study dates
- Jul 2009to Aug 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- Age ≥ 18 years
- Adequate laboratory parameters
- Karnofsky Performance Status ≥ 60
- Life expectancy of at least 3 months
Who cannot join
- 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
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- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Duke University Medical Center
Durham, North Carolina, 27710
Virginia Oncology Associates
Norfolk, Virginia, 23502
About this study
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.
- Conditions
- Prostate Cancer
- Being tested
- Temsirolimus, Diphenhydramine
- Keywords
- metastatic, Temsirolimus, prostate, cancer
- Medical subject headings
- Prostatic Neoplasms, Neoplasm Metastasis, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TemsirolimusDrug
Also called Torisel
dosage form: IV dosage, frequency and duration: 25mg weekly until clinical progression
DiphenhydramineDrug
Also called Benadryl
Dosage form: IV or PO Dosage, frequency and duration: 25-50mg, 30 minutes prior to Temsirolimus infusion
| Study group | Role | What they receive |
|---|---|---|
| Temsirolimus 25 mg | Experimental | 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. Receives: Drug: Temsirolimus; Drug: Diphenhydramine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Circulating Tumor Cell (CTC) Counts in Men With Metastatic Treatment-refractory Castration-resistant 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.
Measured: Baseline to 8 weeks
Secondary outcomes (9)
Percent Change in CTC Count From Baseline to 12 Weeks of Treatment.
To evaluate the change in CTC counts upon the addition of an anti-androgen upon PSA progression while on temsirolimus therapy
Measured: Baseline to 12 weeks
Mean Percent of N-cadherin Expression at Baseline and 8 Weeks of Treatment.
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.
Measured: Baseline and 8 weeks
Percent Change in LDH
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
Measured: Baseline to 12 weeks
Median Progression-Free Survival (PFS)
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.
Measured: 2 years
Maximum Rate of Change of Prostate-Specific Antigen (PSA).
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.
Measured: Baseline to 7 months
Time to PSA Progression
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.
Measured: 2 years
Time to Second PSA Progression After Addition of Anti-androgen Therapy
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.
Measured: 2 years
Change Over Time in CTC Gene Expression Profile
Percent change in CTC gene expression from baseline to 8 or 12 weeks of treatment.
Measured: 12 weeks
Safety and Tolerability of Temsirolimus
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.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2009 (estimated)
- Study startJul 2009
- Primary completionAug 2012
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- National Comprehensive Cancer Network
- Responsible party
- Sponsor
- Investigators
- Andrew Armstrong, MD, ScM, Principal investigator, Duke Unversity Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00887640
- Sponsor's protocol ID
- Pro00016256
- Status last verified
- Jan 2013
- First submitted
- 23 Apr 2009
- Last updated
- 26 Feb 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Temsirolimus Therapy on Circulating Tumor Cell Biology In Men With Castration Resistant Metastatic Prostate Cancer
- ClinicalTrials.gov ID
- NCT00887640
- Acronym / sponsor ID
- Pro00016256
- Conditions
- Prostate Cancer
- Keywords
- metastatic, Temsirolimus, prostate, cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- National Comprehensive Cancer Network
- Study start
- Jul 2009
- Primary completion
- Aug 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 24 Apr 2009 (estimated)
- Results
- Posted 10 Jan 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Temsirolimus 25 mg | Experimental | Drug: Temsirolimus, Drug: DiphenhydramineTemsirolimus 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (23 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TemsirolimusAlso: Toriseldosage form: IV dosage, frequency and duration: 25mg weekly until clinical progression | Drug | Temsirolimus 25 mg |
| DiphenhydramineAlso: BenadrylDosage form: IV or PO Dosage, frequency and duration: 25-50mg, 30 minutes prior to Temsirolimus infusion | Drug | Temsirolimus 25 mg |
Primary outcome
Change in Circulating Tumor Cell (CTC) Counts in Men With Metastatic Treatment-refractory Castration-resistant Prostate Cancer.
Time frame: Baseline to 8 weeks
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.
9 secondary outcomes
Percent Change in CTC Count From Baseline to 12 Weeks of Treatment.
Time frame: Baseline to 12 weeks
Mean Percent of N-cadherin Expression at Baseline and 8 Weeks of Treatment.
Time frame: Baseline and 8 weeks
Percent Change in LDH
Time frame: Baseline to 12 weeks
Median Progression-Free Survival (PFS)
Time frame: 2 years
Maximum Rate of Change of Prostate-Specific Antigen (PSA).
Time frame: Baseline to 7 months
Time to PSA Progression
Time frame: 2 years
Time to Second PSA Progression After Addition of Anti-androgen Therapy
Time frame: 2 years
Change Over Time in CTC Gene Expression Profile
Time frame: 12 weeks
Safety and Tolerability of Temsirolimus
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew Armstrong, MD, ScM principal investigator
Duke Unversity Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Temsirolimus and Diphenhydramine in people with Prostate Cancer, run by Duke University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Jan 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Circulating Tumor Cell (CTC) Counts in Men With Metastatic Treatment-refractory Castration-resistant Prostate Cancer. (time frame: Baseline to 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Feb 2014.