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Trial registered on ANZCTR


Registration number
ACTRN12618000566235
Ethics application status
Approved
Date submitted
16/03/2018
Date registered
13/04/2018
Date last updated
14/01/2024
Date data sharing statement initially provided
18/03/2019
Date results information initially provided
17/09/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
High dose Radiation therapy to eradicate early metastatic prostate cancer as an alternative to hormone or chemotherapy: a prospective phase II study
Scientific title
Ablative Stereotactic Radiotherapy as an alternative to systemic treatment in men with oligometastatic prostate cancer and controlled primary disease. A prospective Phase II study measuring toxicity, disease control and freedom from escalation in systemic therapy
Secondary ID [1] 293970 0
Nil known
Universal Trial Number (UTN)
Trial acronym
TRANSFORM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 306482 0
Condition category
Condition code
Cancer 305579 305579 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Enrolled patients will receive a course of stereotactic radiotherapy delivered five days a week over two weeks. The total dose of radiotherapy will be 50Gy in 10 fractions with 1 fraction delivered daily for 10 consecutive days (excluding weekends and public holidays). If there is overlap with previously delivered radiotherapy fields, an alternate fractionation schedule is acceptable given that an equivalent total dose in 2Gy fractions (EQD2) of at least 60Gy can be maintained.
Radiotherapy will be delivered by a radiation therapy team consisting of suitably qualified personnel and each treatment session will take approximately 10 minutes. The medical physics team is involved in planning prior to treatment to ensure accuracy of treatment delivery. A treatment delivery report will be produced and if any action level is exceeded, including significant internal organ variations or changes in the target volume that were not accommodated by prescribed treatment margins, the treatment plan will be redirected for immediate review and action by the appropriate staff.
Intervention code [1] 300240 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 304701 0
The proportion of patients not requiring treatment escalation at 5 and 10 years. These data will be collected through scheduled patient assessments and medical records.
Timepoint [1] 304701 0
6 weeks post-radiotherapy, three monthly until two years post-radiotherapy, six monthly until five years and then annually up to 10 years post-radiotherapy. The primary outcome will be assessed as time to event over the give year period.
Secondary outcome [1] 342838 0
Length of treatment escalation free survival (oncologist reported or obtained through medical records)
Timepoint [1] 342838 0
6 weeks post-radiotherapy, three monthly until two years post-radiotherapy, six monthly until five years post-radiotherapy and then annually to 10 years.
Secondary outcome [2] 342839 0
Change in % PSA post-treatment (pathological assessment at each follow-up time point)
Timepoint [2] 342839 0
6 weeks post-radiotherapy, three monthly until two years post-radiotherapy, six monthly until five years post-radiotherapy and then annually to 10 years.
Secondary outcome [3] 342842 0
The proportion of patients with no systemic treatment progression and no evaluable cancer at 10 years (i.e. PSA <0.03 ng/mL). This is assessed through the medical record.
Timepoint [3] 342842 0
6 weeks post-radiotherapy, three monthly until two years post-radiotherapy, six monthly until five years post-radiotherapy and then annually to 10 years.
Secondary outcome [4] 405187 0
Rate of SBRT related grade 3 toxicity as measured by CTCAE version 4.0 criteria.
Timepoint [4] 405187 0
6 weeks post-radiotherapy, three monthly until two years post-radiotherapy, six monthly until five years post-radiotherapy and then annually to 10 years.

Eligibility
Key inclusion criteria
- Histologically confirmed diagnosis of prostate cancer.
- Biochemical relapses of prostate cancer following radical local treatment.
- Males aged 18 years to 80 years inclusive.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- N1 and M1 a/b disease on imaging, with a combined maximum of five synchronous lesions
- Exclusion of local relapse.
- Metastases suitable for ablative radiotherapy
Minimum age
18 Years
Maximum age
80 Years
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
- No prior palliative radiotherapy (definitive radiotherapy as part of initial management is allowed).
- Active local disease on clinical examination.

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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
The sample size is based on the precision of estimates of the primary endpoint, the proportion of patients who do not need to go onto next line treatment. A total sample of 200 patients is sufficient to allow exact binomial 95% confidence intervals with a half-width of no greater than 7.5% (i.e., no more than 7.5% on either side of the point estimate), for any proportion. For example, a proportion of 90% would have an exact binomial 95% confidence interval no wider than 90% plus or minus 7.5%.

The primary endpoint of overall proportion of not requiring / cessation of subsequent hormone treatment rates will be assessed using 95% confidence intervals. Time to cessation of hormones will be analysed using Kaplan-Meier curves and median time to event. Association of variables such as Gleason and PSA score, number of treated nodes, with the proportion of patients of no longer requiring further hormones / treatment, and time to cessation will be analysed using binary logistic regression and Cox proportional hazards regression respectively. All statistical tests will be two-tailed, with alpha or statistical significance level set to p < 0.05. 95% confidence intervals will be reported throughout. Analyses will be conducted using standard statistical software such as Stata version 14 (Stata Inc, College Station, Texas) or later, by or under the direction of Epworth HealthCare Biostatistician(s).

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
14/04/2014
Date of last participant enrolment
Anticipated
Actual
22/04/2016
Date of last data collection
Anticipated
27/12/2026
Actual
Sample size
Target
200
Accrual to date
Final
208
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 13428 0
Icon Cancer Centre Richmond - Richmond
Recruitment hospital [2] 13438 0
Icon Cancer Centre Epworth Freemasons - East Melbourne
Recruitment postcode(s) [1] 18783 0
3121 - Richmond
Recruitment postcode(s) [2] 18784 0
3002 - Melbourne

Funding & Sponsors
Funding source category [1] 298601 0
Charities/Societies/Foundations
Name [1] 298601 0
Epworth Medical Foundation
Country [1] 298601 0
Australia
Primary sponsor type
Hospital
Name
Integrated Clinical Oncology Network Pty Ltd (ICON)
Address
Level 1, 22 Cordelia Street, South Brisbane QLD 4101
Country
Australia
Secondary sponsor category [1] 297759 0
None
Name [1] 297759 0
Address [1] 297759 0
Country [1] 297759 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299563 0
Epworth HealthCare HREC
Ethics committee address [1] 299563 0
89 Bridge Road, Richmond VIC 3121
Ethics committee country [1] 299563 0
Australia
Date submitted for ethics approval [1] 299563 0
13/11/2013
Approval date [1] 299563 0
20/02/2014
Ethics approval number [1] 299563 0
622-13
Ethics committee name [2] 302945 0
Monash Health HREC
Ethics committee address [2] 302945 0
246 Clayton Road, Clayton VIC 3168
Ethics committee country [2] 302945 0
Australia
Date submitted for ethics approval [2] 302945 0
Approval date [2] 302945 0
08/03/2019
Ethics approval number [2] 302945 0
RES-19-0000-165E

Summary
Brief summary
Standard treatment for metastatic prostate cancer involves a course of Androgen Deprivation Therapy (ADT). ADT controls disease in about 95% of men for approximately 18 months, however, it can cause considerable side effects that decrease patients quality of life. Stereotactic Ablative Radiotherapy (SABR) has been shown to offer good cancer control rates of around 80% and progression-free survival at two to five years in the vicinity of 20-30% compared to standard RT, while offering the potential benefits of avoiding unpleasant symptoms that may arise from disease progression or side effects from ADT. In our institutions experience, SABR either as a first line therapy, or second line therapy in men who have progressed on hormone therapy, shows a substantial proportion of these patients responded very well, with some men not yet required hormone therapy or actually ceasing further hormone therapy.

The TRANSFORM study is a single-institution, non-randomised, open-label, prospective phase II study that will recruit patients with radiologically confirmed hormone naïve or castration resistant oligometatstaic prostate cancer with the primary aim of measuring the proportion of patients not requiring treatment escalation at 5 and 10 years following SABR, respectively. The TRANSFORM study also aims to measure several secondary outcomesincluding time to treatment escalation, Prostate Specific Antigen (PSA) response, and grade 3 SABR related toxicities.

Patients will be required to undergo a screening and follow up process (for up to
ten years post treatment) that involves physical exams, blood and PSA tests, multiple scans (CT, MRI and PET) as well as questionnaires that help determine how effective the treatment(s) have been in controlling their disease and how that has impacted on their health and lifestyle.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 80850 0
Dr Patrick Bowden
Address 80850 0
Icon Cancer Centre, Level 4, 32 Erin St, Richmond VIC 3121
Country 80850 0
Australia
Phone 80850 0
+61399368277
Fax 80850 0
Email 80850 0
[email protected]
Contact person for public queries
Name 80851 0
Lloyd Smyth
Address 80851 0
Icon Cancer Centre, Level 1, 22 Cordelia Street, South Brisbane, QLD 4101
Country 80851 0
Australia
Phone 80851 0
+61 7 3737 4500
Fax 80851 0
Email 80851 0
[email protected]
Contact person for scientific queries
Name 80852 0
Patrick Bowden
Address 80852 0
Icon Cancer Centre, Level 4, 32 Erin St, Richmond VIC 3121
Country 80852 0
Australia
Phone 80852 0
+61399368277
Fax 80852 0
Email 80852 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
No plans were put in place for data sharing when designing this study and no resources have been allocated to do so.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Bowden, P., See, A.W., Frydenberg, M., Haxhimolla,... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseFractionated stereotactic body radiotherapy for up to five prostate cancer oligometastases: Interim outcomes of a prospective clinical trial.2020https://dx.doi.org/10.1002/ijc.32509
N.B. These documents automatically identified may not have been verified by the study sponsor.