Prostate CancerPhase 1/2NCT01020305
Temsirolimus to Reverse Androgen Insensitivity for Castration-resistant Prostate Cancer
A Phase 1/2 study testing Temsirolimus and Casodex (bicalutamide) in people with Prostate Cancer and Prostatic Neoplasms, run by Sandy Srinivas at 1 site in United States.
Trial summary
This study evaluates if temsirolimus causes a reduction in the serum levels of prostate-specific antigen (PSA) in male subjects with castration-resistant prostate cancer (CRPC). Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer, Prostatic Neoplasms, Castrate-resistant Prostate Cancer (CRPC)
- What is being tested?
- Temsirolimus and Casodex (bicalutamide)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2009to Apr 2012
- Phase
- Phase 1/2
- 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 adenocarcinoma of the prostate, characterized as symptomatic castration-resistant prostate cancer (CRPC)
- Serum PSA ≥ 2 ng/mL
- Rising PSA on 3 consecutive occasions at least 1 week apart (not limited to the 30-day screening period)
- Failure of bilateral orchiectomy and/or therapy with an LHRH agonist and bicalutamide
- Castrate level of testosterone (< 50 ng/dL)
- Currently being treated with bicalutamide
Show all 14Show fewer
- No prior antiandrogen therapy except bicalutamide
- Age ≥ 18 years
- Life expectancy > 6 months
- Performance status
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- OR
- Karnofsky performance status ≥ 80%
- Ability to understand and the willingness to sign a written informed consent
Who cannot join
- Radiotherapy for prostate cancer within 28 days prior to Day 1, except single-fraction radiotherapy for pain control
- Prior treatment with mTOR inhibitors
- Prior treatment with chemotherapy for prostate cancer
- Symptomatic bone metastases (ie, asymptomatic bone metastases are eligible)
- Visceral metastases
- Absolute neutrophil count (ANC) < 1500/uL
Show all 28Show fewer
- Platelet count ≤ 100 x 10e9/L
- Total bilirubin ≥ 1.5 x Upper Limit of Normal (ULN)
- Alkaline phosphatase > 2.5 x ULN
- AST > 2.5 x ULN
- ALT > 2. 5x ULN
- Serum creatinine > 2.0 mg/dL
- Hemoglobin < 9 g/dL
- Men with reproductive potential who do not agree to use an accepted and effective method of contraception during the study treatment period and for at least 3 months after completion of the study treatment
- History of other malignancies within 5 years except for tumors with a negligible risk for metastasis or death, such as adequately-controlled basal cell carcinoma, squamous-cell carcinoma of the skin, or early-stage bladder cancer
- Participation in another experimental drug study either planned or within 4 weeks of the first study treatment
- Persistent Grade ≥ 1 AEs due to prior drug therapy, including investigational drugs, administered more than 14 days before study enrollment
- Previously treated or other known brain metastases
- Ongoing or active infection
- Symptomatic congestive heart failure, New York Heart Association Grade II or greater
- Unstable angina pectoris
- Cardiac arrhythmia
- Significant vascular disease (eg, aortic aneurysm, aortic dissection)
- Symptomatic peripheral vascular disease
- Psychiatric illness/social situations that would limit compliance with study requirements
- Other uncontrolled intercurrent illness
- Known to be positive for the human immunodeficiency virus (HIV) infection and receiving antiretroviral therapies (HIV positive not requiring antiretroviral therapy iseligible if all other entry criteria are meet)
- Inability to comply with study and/or follow-up procedures
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University School of Medicine
Stanford, California, 94305
About this study
Official title: Temsirolimus, an mTOR Inhibitor, to Reverse Androgen Insensitivity in Patients With Castration-resistant Prostate Cancer
This study evaluates if temsirolimus causes a reduction in the serum levels of prostate-specific antigen (PSA) in male subjects with castration-resistant prostate cancer (CRPC).
Read the detailed description
Castration-resistant prostate cancer (CRPC) is also known as "androgen-insensitive" or "hormone-refractory" prostate cancer. While numerous therapies impact biochemical response in the setting of CRPC, there remains unmet medical need. New therapies that extend survival of patients beyond that provided by chemotherapy are needed.
The mechanisms of tumor progression to castration-resistance are unclear, but preclinical studies suggest that functional loss of the tumor suppressor gene PTEN and subsequent up-regulation of Akt, which is upstream of mTOR, may be involved in prostate cancer progression and metastasis. Based on these observations, it is hypothesized that mTOR inhibitor temsirolimus may prolong hormone sensitivity and delay disease progression in castration-resistant prostate cancer patients before antiandrogen withdrawal.
This study will assess efficacy on the basis of serum levels of PSA, an established surrogate endpoint for efficacy in prostate cancer.
- Conditions
- Prostate Cancer, Prostatic Neoplasms, Castrate-resistant Prostate Cancer (CRPC), Androgen-insensitive Prostate Cancer, Hormone-refractory Prostate Cancer, Metastatic Disease
- Being tested
- Temsirolimus, Casodex (bicalutamide)
- Medical subject headings
- Prostatic Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TemsirolimusDrug
Also called Torisel, CCI-779
Temsirolimus is an inhibitor of the mammalian target of rapamycin (MTOR, aka HGNC:3942)
IUPAC name: (1R,2R,4S)-4-{(2R)-2-[(3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,27-dihydroxy-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-1,5,11,28,29-pentaoxo-1,4,5,6,9,10,11,12,13,14,21,22,23,24,25,26,27,28,29,31,32,33,34,34a-tetracosahydro-3H-23,27-epoxypyrido[2,1-c][1,4]oxazacyclohentriacontin-3-yl]propyl}-2-methoxycyclohexyl 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate
Casodex (bicalutamide)Drug
Also called Casodex, bicalutamide, Cosudex, Calutide
Casodex (bicalutamide) 50 mg/day PO
| Study group | Role | What they receive |
|---|---|---|
| Temsirolimus + Bicalutamide | Experimental | Temsirolimus 25 mg administered intravenously (IV) once weekly for 12 weeks
Casodex (bicalutamide) administered 50 mg/day orally (PO) Receives: Drug: Temsirolimus; Drug: Casodex (bicalutamide) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction in Serum PSA
Proportion of subjects with > 50% drop in serum PSA as compared to baseline, assessed at 16 weeks
Measured: 12 weeks treatment, with primary outcome assessed at 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2009 (estimated)
- Study startOct 2009
- Primary completionApr 2012
- Study completionApr 2012
Why it stopped: Decision by funding sponsor due to poor accrual
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.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sandy Srinivas
- Sponsor type
- University, hospital or other
- Collaborators
- Wyeth is now a wholly owned subsidiary of Pfizer, National Comprehensive Cancer Network, American Society of Clinical Oncology
- Responsible party
- Sponsor-investigator, Sandy Srinivas, Stanford University
- Investigators
- Sandhya "Sandy" Srinivas, MD, Principal investigator, Stanford UniversityLauren Christine Harshman, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01020305
- Sponsor's protocol ID
- IRB-17242
- Other IDs
- NCT01020305, SU-09292009-4080, PROS0028
- Status last verified
- Oct 2014
- First submitted
- 30 Oct 2009
- Last updated
- 13 Oct 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 13 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Temsirolimus, an mTOR Inhibitor, to Reverse Androgen Insensitivity in Patients With Castration-resistant Prostate Cancer
- ClinicalTrials.gov ID
- NCT01020305
- Acronym / sponsor ID
- IRB-17242
- Conditions
- Prostate Cancer, Prostatic Neoplasms, Castrate-resistant Prostate Cancer (CRPC), Androgen-insensitive Prostate Cancer, Hormone-refractory Prostate Cancer, Metastatic Disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Decision by funding sponsor due to poor accrual
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Sandy SrinivasUniversity, hospital or other
- Collaborators
- Wyeth is now a wholly owned subsidiary of Pfizer, National Comprehensive Cancer Network, American Society of Clinical Oncology
- Study start
- Oct 2009
- Primary completion
- Apr 2012 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 25 Nov 2009 (estimated)
- Results
- Posted 13 Oct 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates if temsirolimus causes a reduction in the serum levels of prostate-specific antigen (PSA) in male subjects with castration-resistant prostate cancer (CRPC).
Detailed description
Castration-resistant prostate cancer (CRPC) is also known as "androgen-insensitive" or "hormone-refractory" prostate cancer. While numerous therapies impact biochemical response in the setting of CRPC, there remains unmet medical need. New therapies that extend survival of patients beyond that provided by chemotherapy are needed.
The mechanisms of tumor progression to castration-resistance are unclear, but preclinical studies suggest that functional loss of the tumor suppressor gene PTEN and subsequent up-regulation of Akt, which is upstream of mTOR, may be involved in prostate cancer progression and metastasis. Based on these observations, it is hypothesized that mTOR inhibitor temsirolimus may prolong hormone sensitivity and delay disease progression in castration-resistant prostate cancer patients before antiandrogen withdrawal.
This study will assess efficacy on the basis of serum levels of PSA, an established surrogate endpoint for efficacy in prostate cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Temsirolimus + Bicalutamide | Experimental | Drug: Temsirolimus, Drug: Casodex (bicalutamide)Temsirolimus 25 mg administered intravenously (IV) once weekly for 12 weeks Casodex (bicalutamide) administered 50 mg/day orally (PO) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Histologically-confirmed adenocarcinoma of the prostate, characterized as symptomatic castration-resistant prostate cancer (CRPC)
- Serum PSA ≥ 2 ng/mL
- Rising PSA on 3 consecutive occasions at least 1 week apart (not limited to the 30-day screening period)
- Failure of bilateral orchiectomy and/or therapy with an LHRH agonist and bicalutamide
- Castrate level of testosterone (< 50 ng/dL)
Key exclusion criteria (28 listed)
- Radiotherapy for prostate cancer within 28 days prior to Day 1, except single-fraction radiotherapy for pain control
- Prior treatment with mTOR inhibitors
- Prior treatment with chemotherapy for prostate cancer
- Symptomatic bone metastases (ie, asymptomatic bone metastases are eligible)
- Visceral metastases
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: Torisel, CCI-779Temsirolimus is an inhibitor of the mammalian target of rapamycin (MTOR, aka HGNC:3942) IUPAC name: (1R,2R,4S)-4-{(2R)-2-[(3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,27-dihydroxy-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-1,5,11,28,29-pentaoxo-1,4,5,6,9,10,11,12,13,14,21,22,23,24,25,26,27,28,29,31,32,33,34,34a-tetracosahydro-3H-23,27-epoxypyrido[2,1-c][1,4]oxazacyclohentriacontin-3-yl]propyl}-2-methoxycyclohexyl 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate | Drug | Temsirolimus + Bicalutamide |
| Casodex (bicalutamide)Also: Casodex, bicalutamide, Cosudex, CalutideCasodex (bicalutamide) 50 mg/day PO | Drug | Temsirolimus + Bicalutamide |
Primary outcome
Reduction in Serum PSA
Time frame: 12 weeks treatment, with primary outcome assessed at 16 weeks
Proportion of subjects with > 50% drop in serum PSA as compared to baseline, assessed at 16 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 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.
Sandhya "Sandy" Srinivas, MD principal investigator
Stanford University
Lauren Christine Harshman, MD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Temsirolimus and Casodex (bicalutamide) in people with Prostate Cancer and Prostatic Neoplasms, run by Sandy Srinivas at 1 site 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 14 inclusion and 28 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 13 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 13 Oct 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?
Reduction in Serum PSA (time frame: 12 weeks treatment, with primary outcome assessed at 16 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 13 Oct 2014.