Prostate CancerPhase 2DAPROCA-1NCT01000948
A Safety Study of ZD4054 in Prior Chemotherapy Treated Patients With Metastatic Hormone-resistant Prostate Cancer
A Phase 2 study testing ZD4054 in people with Prostate Cancer and Metastasis, run by Aarhus University Hospital at 1 site in Denmark.
Trial summary
This is a prospective, open, one-arm, two-centre, Phase II clinical safety pilot-study. The trial is designed to gain initial safety and efficacy-related data on once-daily orally administered ZD4054 10 mg in prior chemotherapy treated patients with metastatic hormone-resistant prostate cancer. Read more about this study
- Who is it for?
- Ages 18 to 90 years, men only
- Conditions the study is for
- Prostate Cancer, Metastasis
- What is being tested?
- ZD4054
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteDenmark
- Study dates
- Oct 2009to Jul 2011
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 to 90 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of informed consent
- Male, aged 18 years or older
- Histological or cytological confirmation of adenocarcinoma of the prostate
- Documented evidence of bone metastasis on bone scans.
- Surgically castrated or continuously medically castrated with serum testosterone less than 2.4 nmol/L (70 ng/dL).
- Previously (not inside 8 weeks) treated with at least two times 75 mg/m2 docetaxel.
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- Biochemical progression of prostate cancer after chemotherapy, documented while the patient is castrate:
- o Biochemical progression is defined as at least 2 stepwise increases (≥1ng/mL) in PSA over a period of ≥1 month (values do not need to be consecutive but 2 values that have increased since the previous highest value are required) with at least 14 days between each measurement irrespective of assay or laboratory.
- Life expectancy of 3 months or more.
Who cannot join
- Use of potent CYP450 inducers (such as phenytoin, rifampicin, carbamazepine, phenobarbitone and St John's Wort) within 2 weeks of starting study treatment. Dexamethasone will be allowed if the investigator feels it is necessary but is encouraged to use a different form of steroid treatment wherever possible
- Have received investigational drug in another clinical study of anticancer therapy, within 4 weeks of starting study treatment
- Hypersensitivity to endothelin antagonists
- Neurological symptoms or signs consistent with acute or evolving spinal cord compression. If a patient has neurologic symptoms, an MRI must be performed that demonstrates no impending or actual spinal cord compression. Stable, previously treated patients are allowed
- History of past or current epilepsy, epilepsy syndrome, or other seizure disorder
- Stage II, III or IV cardiac failure (classified according to New York Heart Association (NYHA) classification) or myocardial infarction within 6 months prior to study entry
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- QT interval corrected for heart rate e.g., by Bazett's correction >470 msec
- In the opinion of the investigator, any evidence of severe or uncontrolled systemic disease (e.g., currently unstable or uncompensated respiratory, cardiac, hepatic or renal disease) or evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study
- Hemoglobin (Hb) <5 mmol/L. Concomitant use of erythropoietin or blood transfusions is allowed
- Serum bilirubin >1.5 times the upper limit of normal (ULN). This will not apply to patients with Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of evidence of haemolysis or hepatic pathology), who will be allowed in consultation with their physician
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 times the ULN or 5 times the ULN in the presence of liver metastasis
- Creatinine clearance of <50 mL/minute, determined using the Cockcroft-Gault equation or by 24-hour creatinine clearance
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open Phase II, Two-centre, 1-Arm Safety Study of Once-daily Orally Administered 10 mg ZD4054 in Prior Chemotherapy Treated Patients With Metastatic Hormone-resistant Prostate Cancer
This is a prospective, open, one-arm, two-centre, Phase II clinical safety pilot-study. The trial is designed to gain initial safety and efficacy-related data on once-daily orally administered ZD4054 10 mg in prior chemotherapy treated patients with metastatic hormone-resistant prostate cancer.
Read the detailed description
Study centres and number of patients planned This pilot study will be conducted in approximately 24 patients recruited from two hospital-based Danish centres: department of Urology K, Aarhus University Hospital, Skejby and department of Urologic Surgery D, Rigshospitalet. The recruitment of patients will be competitive among centres. 1-2 months before expected LSI it should be discussed if the target accrual should be expanded.
Study period Phase of development Estimated date of first patient enrolled August 1th 2009 II Estimated date of last patient completed July 31th 2012 Total study duration is approximately 36 months, which includes 12 months' recruitment, 36-month follow-up for safety and final survival analysis.
Objectives
The primary objective of this study is:
To assess the safety and tolerability profile of ZD4054 after treatment with chemotherapy
- Adverse events
- Vital signs
- Laboratory data
- ECGs
- Physical Exam
- Death from any cause
The secondary objectives of the study are:
- To investigate the effect of ZD4054 on rate of rise of PSA
- To investigate the effect of ZD4054 on prostate cancer related pain
- To investigate the effect of ZD4054 on the plasma concentration of circulating tumour cells (CTC).
In addition, Time to Progression and Overall Survival (time to death) will be compared with historical data in a post chemotherapy population.
Study design This is a prospective, Open, One-arm, Phase II clinical safety pilot-study. The trial is designed to gain initial safety and efficacy-related data on once-daily orally administered ZD4054 10 mg in prior chemotherapy treated patients with metastatic hormone-resistant prostate cancer.
Patients could receive other therapies including prednisolone, estramustine, ketoconazole and second-line or third-line antiandrogens at investigator's discretion without being considered treatment failures or having to stop study therapy; however every attempt will be made to avoid changes in medication for at least 12 weeks to minimise potential for confounding on study endpoints over this time period. Chemotherapy and radiation therapy may also be administered in addition to study therapy at investigator's discretion after objective progression if the patient is considered likely to derive benefit. Patients will be followed to death.
Target patient population A total number of 24 male patients aged 18 years or older with metastatic hormone-resistant prostate cancer who have progressive disease (defined by rising serum prostate-specific antigen levels despite medical or surgical castration) and previously received cytotoxic chemotherapy (docetaxel) for the treatment of HRPC.
Investigational product, dosage and mode of administration
Patients will not be randomised and all patients will receive:
- ZD4054 10 mg given orally, once daily in tablet form. Duration of treatment Patients will receive daily ZD4054 as long as they meet no withdrawal criteria. Following completion of 24 months of ZD4054, patients, who in the investigator's opinion are experiencing benefit from study treatment, may continue on ZD4054, for as long as they meet no withdrawal criteria.
Statistical methods The study is a pilot study designed to collect safety/tolerability data and assess markers of efficacy. A total of 24 patients will be recruited into this pilot study and this is based primarily on the number of patients that can be recruited in a reasonable time period at the centres and should be sufficient to make an initial assessment of safety/tolerability and the efficacy markers.
For the assessment of tolerability and safety, incidence and severity of adverse events (AEs) (based on National Cancer Institute Common Terminology Criteria for Adverse Events, version 3 (NCI CTCAE) grading), laboratory values, vital signs, ECGs and physical exam will be summarised.
Secondary endpoints will be presented and analysed to investigate trends in the data. The interpretation of the analyses will consider the number of assessments being undertaken.
Pain will be assessed using the Brief Pain Inventory Demography and baseline data will be summarised. Any analyses will be performed using SPSS and other validated software as appropriate.
- Conditions
- Prostate Cancer, Metastasis
- Being tested
- ZD4054
- Keywords
- Prostate cancer, Castration resistant, Chemotherapy resistant, Endothelial receptor A inhibitor, ZD4054
- 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.
ZD4054Drug
ZD4054 10 mg given orally, once daily in tablet form to all patients in two years or until investigator consider the drug for useless.
| Study group | Role | What they receive |
|---|---|---|
| ZD4054 | Experimental | The study had only one arm: intervention Receives: Drug: ZD4054 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the safety and tolerability profile of ZD4054 after treatment with chemotherapy
Measured: 2 years
Adverse events
Measured: 2 years
Vital signs
Measured: 2 years
Laboratory data
Measured: 2 years
ECGs
Measured: 2 years
Physical Exam
Measured: 2 years
Death from any cause
Measured: 2 years
Secondary outcomes (3)
To investigate the effect of ZD4054 on rate of rise of PSA
Measured: 2 years
To investigate the effect of ZD4054 on prostate cancer related pain
Measured: 2 years
To investigate the effect of ZD4054 on the plasma concentration of circulating tumour cells (CTC).
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 posted23 Oct 2009 (estimated)
- Study startOct 2009
- Primary completionJul 2011
- Study completionJul 2011
Why it stopped: A consequence of the results of the ENTHUSE phase III study program
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by Aarhus University HospitalThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aarhus University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet
- Responsible party
- Principal investigator, Michael Borre, Aarhus University Hospital
- Investigators
- Michael Borre, MD Phd DMSc, Study chair, Dpt Urology Aarhus University Hospital - DAPROCA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01000948
- Sponsor's protocol ID
- ISSIS40540005
- Other IDs
- DAPROCA-1
- Acronym
- DAPROCA-1
- Status last verified
- Jul 2011
- First submitted
- 22 Oct 2009
- Last updated
- 8 Jan 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Phase II, Two-centre, 1-Arm Safety Study of Once-daily Orally Administered 10 mg ZD4054 in Prior Chemotherapy Treated Patients With Metastatic Hormone-resistant Prostate Cancer
- ClinicalTrials.gov ID
- NCT01000948
- Acronym / sponsor ID
- DAPROCA-1 / ISSIS40540005
- Conditions
- Prostate Cancer, Metastasis
- Keywords
- Prostate cancer, Castration resistant, Chemotherapy resistant, Endothelial receptor A inhibitor, ZD4054
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: A consequence of the results of the ENTHUSE phase III study program
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Aarhus University HospitalUniversity, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet
- Study start
- Oct 2009
- Primary completion
- Jul 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 23 Oct 2009 (estimated)
- Results
- Not posted in the source record
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 prospective, open, one-arm, two-centre, Phase II clinical safety pilot-study. The trial is designed to gain initial safety and efficacy-related data on once-daily orally administered ZD4054 10 mg in prior chemotherapy treated patients with metastatic hormone-resistant prostate cancer.
Detailed description
Study centres and number of patients planned This pilot study will be conducted in approximately 24 patients recruited from two hospital-based Danish centres: department of Urology K, Aarhus University Hospital, Skejby and department of Urologic Surgery D, Rigshospitalet. The recruitment of patients will be competitive among centres. 1-2 months before expected LSI it should be discussed if the target accrual should be expanded.
Study period Phase of development Estimated date of first patient enrolled August 1th 2009 II Estimated date of last patient completed July 31th 2012 Total study duration is approximately 36 months, which includes 12 months' recruitment, 36-month follow-up for safety and final survival analysis.
Objectives
The primary objective of this study is:
To assess the safety and tolerability profile of ZD4054 after treatment with chemotherapy
- Adverse events
- Vital signs
- Laboratory data
- ECGs
- Physical Exam
- Death from any cause
The secondary objectives of the study are:
- To investigate the effect of ZD4054 on rate of rise of PSA
- To investigate the effect of ZD4054 on prostate cancer related pain
- To investigate the effect of ZD4054 on the plasma concentration of circulating tumour cells (CTC).
In addition, Time to Progression and Overall Survival (time to death) will be compared with historical data in a post chemotherapy population.
Study design This is a prospective, Open, One-arm, Phase II clinical safety pilot-study. The trial is designed to gain initial safety and efficacy-related data on once-daily orally administered ZD4054 10 mg in prior chemotherapy treated patients with metastatic hormone-resistant prostate cancer.
Patients could receive other therapies including prednisolone, estramustine, ketoconazole and second-line or third-line antiandrogens at investigator's discretion without being considered treatment failures or having to stop study therapy; however every attempt will be made to avoid changes in medication for at least 12 weeks to minimise potential for confounding on study endpoints over this time period. Chemotherapy and radiation therapy may also be administered in addition to study therapy at investigator's discretion after objective progression if the patient is considered likely to derive benefit. Patients will be followed to death.
Target patient population A total number of 24 male patients aged 18 years or older with metastatic hormone-resistant prostate cancer who have progressive disease (defined by rising serum prostate-specific antigen levels despite medical or surgical castration) and previously received cytotoxic chemotherapy (docetaxel) for the treatment of HRPC.
Investigational product, dosage and mode of administration
Patients will not be randomised and all patients will receive:
- ZD4054 10 mg given orally, once daily in tablet form. Duration of treatment Patients will receive daily ZD4054 as long as they meet no withdrawal criteria. Following completion of 24 months of ZD4054, patients, who in the investigator's opinion are experiencing benefit from study treatment, may continue on ZD4054, for as long as they meet no withdrawal criteria.
Statistical methods The study is a pilot study designed to collect safety/tolerability data and assess markers of efficacy. A total of 24 patients will be recruited into this pilot study and this is based primarily on the number of patients that can be recruited in a reasonable time period at the centres and should be sufficient to make an initial assessment of safety/tolerability and the efficacy markers.
For the assessment of tolerability and safety, incidence and severity of adverse events (AEs) (based on National Cancer Institute Common Terminology Criteria for Adverse Events, version 3 (NCI CTCAE) grading), laboratory values, vital signs, ECGs and physical exam will be summarised.
Secondary endpoints will be presented and analysed to investigate trends in the data. The interpretation of the analyses will consider the number of assessments being undertaken.
Pain will be assessed using the Brief Pain Inventory Demography and baseline data will be summarised. Any analyses will be performed using SPSS and other validated software as appropriate.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ZD4054 | Experimental | Drug: ZD4054The study had only one arm: intervention |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Provision of informed consent
- Male, aged 18 years or older
- Histological or cytological confirmation of adenocarcinoma of the prostate
- Documented evidence of bone metastasis on bone scans.
- Surgically castrated or continuously medically castrated with serum testosterone less than 2.4 nmol/L (70 ng/dL).
Key exclusion criteria (12 listed)
- Use of potent CYP450 inducers (such as phenytoin, rifampicin, carbamazepine, phenobarbitone and St John's Wort) within 2 weeks of starting study treatment. Dexamethasone will be allowed if the investigator feels it is necessary but is encouraged to use a different form of steroid treatment wherever possible
- Have received investigational drug in another clinical study of anticancer therapy, within 4 weeks of starting study treatment
- Hypersensitivity to endothelin antagonists
- Neurological symptoms or signs consistent with acute or evolving spinal cord compression. If a patient has neurologic symptoms, an MRI must be performed that demonstrates no impending or actual spinal cord compression. Stable, previously treated patients are allowed
- History of past or current epilepsy, epilepsy syndrome, or other seizure disorder
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 |
|---|---|---|
| ZD4054ZD4054 10 mg given orally, once daily in tablet form to all patients in two years or until investigator consider the drug for useless. | Drug | ZD4054 |
Primary outcome
To assess the safety and tolerability profile of ZD4054 after treatment with chemotherapy
Time frame: 2 years
Adverse events
Time frame: 2 years
Vital signs
Time frame: 2 years
Laboratory data
Time frame: 2 years
ECGs
Time frame: 2 years
Physical Exam
Time frame: 2 years
Death from any cause
Time frame: 2 years
3 secondary outcomes
To investigate the effect of ZD4054 on rate of rise of PSA
Time frame: 2 years
To investigate the effect of ZD4054 on prostate cancer related pain
Time frame: 2 years
To investigate the effect of ZD4054 on the plasma concentration of circulating tumour cells (CTC).
Time frame: 2 years
Results and safety
The study was stopped early (reason given: A consequence of the results of the ENTHUSE phase III study program). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2014.
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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.
Michael Borre, MD Phd DMSc study chair
Dpt Urology Aarhus University Hospital - DAPROCA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ZD4054 in people with Prostate Cancer and Metastasis, run by Aarhus University Hospital at 1 site in Denmark.
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 9 inclusion and 12 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 8 Jan 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 Denmark. 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?
The study was stopped early (reason given: A consequence of the results of the ENTHUSE phase III study program). Results are not available in the source record.
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?
To assess the safety and tolerability profile of ZD4054 after treatment with chemotherapy (time frame: 2 years). The study lists 7 primary outcomes in all. 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 8 Jan 2014.