Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000784819
Ethics application status
Approved
Date submitted
7/05/2021
Date registered
22/06/2021
Date last updated
1/09/2024
Date data sharing statement initially provided
22/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A preliminary study of the addition of prazosin to radiotherapy in men with prostate cancer
Scientific title
A feasibility study of the repurposing of prazosin to improve treatment outcomes in men receiving radiotherapy for prostate cancer (MiniRaP-00)
Secondary ID [1] 304161 0
Nil known
Universal Trial Number (UTN)
Trial acronym
MiniRaP-00
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 321855 0
Condition category
Condition code
Cancer 319582 319582 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This trial will be a feasibility study with dose escalation of the investigational drug (prazosin). The study will follow a standard 3 + 3 model followed by dose expansion. Each participant will remain on the same dose level throughout their treatment. Once dose escalation is complete all new participants will then be enrolled into the dose expansion phase. During the 3 + 3 phase, three participants will be enrolled to each dose level. If there are no dose limiting toxicities (DLT) at the respective dose level the study will proceed to the next level. If one patient develops a DLT then an additional three patients will be enrolled into the dose level, should a second participant develop at DLT at the same level then the previous dose level will be defined as the maximum tolerated dose. It is planned that there will be 6 dose levels, 0.5mg, 1mg, 2mg, 3mg, 4mg and 5mg (all dosed twice daily), however if DLTs occur higher dose levels may not be reached.
Participants will commence prazosin one week prior to the commencement of radiotherapy. Prazosin will be provided as 1mg, 2mg and 5mg tablets and dosing will commence one week prior to radiotherapy to enable dose titration and continue until the end of radiotherapy, approximately 4-6 weeks based on prescribed radiotherapy treatment plan. The appropriate tablet strength will be provided to the participant based on their dosing level.
Participants will be enrolled into either the 0.5mg, 1mg, 2mg, 3mg, 4mg or 5mg dose levels, dosed twice daily. All patients will be commenced on 0.5mg (half of a 1mg tablet) of prazosin to be taken twice daily one week prior to the commencement of radiotherapy. For subsequent dose levels, the dose will be increased weekly.
Compliance will be assessed at weekly review by the returning of all medication packaging and unused tablets. Participants will also be required to complete a dosing diary for the duration of treatment.
Intervention code [1] 320493 0
Treatment: Drugs
Comparator / control treatment
Nil
Control group
Uncontrolled

Outcomes
Primary outcome [1] 327438 0
Protocol and treatment schedule compliance as a composite outcome. Compliance feasibility will be defined as = 80% compliance rate to the study protocol/treatment schedule. Treatment compliance will be defined as participants missing < 10% of prazosin doses and being able to complete all radiotherapy fractions. Treatment compliance will be assessed using participant dosing diaries and the return of medication packaging and unused tablets. Assessment compliance will be defined as a completion of = 80% required assessments.
Timepoint [1] 327438 0
At the completion of radiotherapy and prazosin treatment.
Secondary outcome [1] 395128 0
PSA Kinetics - PSA kinetics will be measured by the calculation of PSA velocity and PSA doubling time as a composite outcome. Analysis of PSA kinetics will provide data on short-term efficacy of the addition of prazosin to radiotherapy. PSA kinetics will be measured using PSA levels taken at three, six and nine months post radiotherapy. PSA velocity and PSA doubling time will be calculated using regression models. PSA values will be retrieved from standard of care blood test post radiotherapy.
Timepoint [1] 395128 0
At 12, 24 and 36 weeks post radiotherapy.
Secondary outcome [2] 395129 0
Chemical or biochemical progression free survival - Clinical or biochemical progression free survival is defined as the time from the start of prazosin to the date of first clinical or biochemical evidence of disease progression or recurrence or death from any cause, whichever comes first.
Clinical evidence of disease progression or recurrence includes imaging (CT/MRI or whole-body radioisotope bone scan), pathology indicative of biochemical relapse, presentation of symptoms attributable to disease progression or recurrence or commencement of other anticancer treatment for prostate cancer.
Timepoint [2] 395129 0
At completion of 12 month follow-up period.
Secondary outcome [3] 395130 0
Adverse events - The National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) V5.0 will be used to classify and grade any adverse events occurring up to 30 days after the last dose of the study drug.
The RTOG/EORTC toxicity criteria will be used to assess morbidities related to radiotherapy. Radiation toxicity will be defined as either acute or late. Acute toxicities are defined as those occurring within 12 weeks of the commencement of radiotherapy and scored according to the RTOG/EORTC Acute Radiation Morbidity Scoring Criteria. Late toxicities will be defined as those that occur more than 12 weeks after the commencement of radiotherapy and will be classified by the RTOG/EORTC Late Radiation Morbidity Scoring Schema.
Timepoint [3] 395130 0
Weekly during treatment, at completion of radiotherapy and prazosin treatment and at 12, 24, and 36 weeks post radiotherapy.
Secondary outcome [4] 395131 0
Maximum tolerated dose of prazosin - This study will be used to determine the maximum tolerated dose of prazosin when used in conjunction with radiotherapy for the treatment of prostate cancer. This dose will be determined based on the ability of participants to complete the planned prazosin dose titration schedule using a participant dosing diary and assessment of compliance of the returned of unused tablet at weekly reviews . If all participants are able to tolerate the ceiling dose of 5mg twice daily, this dose will be defined as the maximum tolerated dose.
Timepoint [4] 395131 0
At completion of prazosin treatment for all participants.

Eligibility
Key inclusion criteria
- Histologically confirmed adenocarcinoma of the prostate
- Age greater or equal to 18 years
- Normal liver function: ALT <2x ULN, Bilirubin <1.5 x ULN or normal conjugated bilirubin
- Normal renal function: Serum urea and creatinine <1.5 ULN
- ECOG performance status of 0-1
- Participants capable of childbearing only if using adequate contraception
- Willingness to comply with all study procedures including IP administration protocol and required testing
- Signed, written and informed consent
- Participants are available for follow up
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
- Evidence of >5 metastatic sites: Suspected or confirmed by appropriate imaging.
- Under the age of 18 years
- Presence of any medical, psychological or social condition that may hinder compliance
- Use of hormonal therapy more than 30 days prior to commencement of prazosin, other than ADT prescribed for the treatment of PCa
- History of any other previous malignancy within 5 years of the commencement of prazosin, other than successfully treated squamous cell or basal cell carcinoma of the skin
- Has received prior brachytherapy or radiotherapy for PCa to the same site
- Planned treatment with brachytherapy
- Planned treatment with stereotactic ablative body radiotherapy (SABR)
- Pre-existing hypotension defined as: Seated blood pressure < 100 mmHg systolic and/or < 70 mmHg diastolic
- Pre-existing orthostatic hypotension defined as: Decrease in systolic blood pressure of 20 mm Hg or a decrease in diastolic blood pressure of 10 mm Hg within three minutes of standing when compared with seated blood pressure
- Allergy to quinazolines
- Treatment with a1-antagonists with the last 6 months: Including all drugs within the class e.g. tamsulosin, silodosin, doxazosin, alfuzosin and prazosin
- Pre-existing cataract disease where cataract surgery is planned during the time that the patient would be receiving prazosin
- Patients are high falls risk as assessed by physician
- Planned cataract surgery
- Concurrent participation in other clinical trials or use of other investigational products
- Known gastrointestinal disease that could affect the absorption or tolerance of the IP

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
1/07/2021
Actual
28/10/2022
Date of last participant enrolment
Anticipated
31/07/2024
Actual
4/06/2024
Date of last data collection
Anticipated
30/06/2025
Actual
Sample size
Target
30
Accrual to date
Final
10
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 19343 0
Genesis Cancer Care - Southport - Southport
Recruitment hospital [2] 19344 0
Genesis Cancer Care - Tugun - Tugun
Recruitment postcode(s) [1] 33926 0
4215 - Southport
Recruitment postcode(s) [2] 33927 0
4224 - Tugun

Funding & Sponsors
Funding source category [1] 308533 0
Charities/Societies/Foundations
Name [1] 308533 0
GenesisCare Foundation
Country [1] 308533 0
Australia
Funding source category [2] 308542 0
University
Name [2] 308542 0
Griffith University
Country [2] 308542 0
Australia
Primary sponsor type
Other
Name
GenesisCare
Address
Buildings 1&11, The Mill, 41-43 Bourke Road, Alexandria, NSW, 2015.
Country
Australia
Secondary sponsor category [1] 309392 0
None
Name [1] 309392 0
Address [1] 309392 0
Country [1] 309392 0
Other collaborator category [1] 281774 0
University
Name [1] 281774 0
Griffith University
Address [1] 281774 0
1 Parklands Drive, Southport, QLD, 4215
Country [1] 281774 0
Australia
Other collaborator category [2] 281775 0
Commercial sector/Industry
Name [2] 281775 0
Ramsay Pharmacy
Address [2] 281775 0
Level 2, 479 St Kilda Road, Melbourne Vic 3004
Country [2] 281775 0
Australia
Other collaborator category [3] 281776 0
University
Name [3] 281776 0
Bond University
Address [3] 281776 0
14 University Drive, Robina, QLD, 4226
Country [3] 281776 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308488 0
Ramsay Health Care Qld HREC, Greenslopes Private Hospital
Ethics committee address [1] 308488 0
Ethics committee country [1] 308488 0
Australia
Date submitted for ethics approval [1] 308488 0
01/12/2020
Approval date [1] 308488 0
16/02/2021
Ethics approval number [1] 308488 0
20/32

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 110874 0
Prof David Christie
Address 110874 0
GenesisCare Tugun, 42 Inland Drive, Tugun, QLD, 4224
Country 110874 0
Australia
Phone 110874 0
+61755073672
Fax 110874 0
Email 110874 0
[email protected]
Contact person for public queries
Name 110875 0
Liam King
Address 110875 0
Ramsay Pharmacy John Flynn Hospital, Level 1, 42 Inland Drive, Tugun, QLD, 4224
Country 110875 0
Australia
Phone 110875 0
+61 755989155
Fax 110875 0
Email 110875 0
[email protected]
Contact person for scientific queries
Name 110876 0
Liam King
Address 110876 0
Ramsay Pharmacy John Flynn Hospital, Level 1, 42 Inland Drive, Tugun, QLD, 4224
Country 110876 0
Australia
Phone 110876 0
+61 755989155
Fax 110876 0
Email 110876 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.