ANZCTR - Registration

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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

18/03/2019

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]

Nil known

Universal Trial Number (UTN)

Trial acronym

TRANSFORM

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Prostate Cancer

Condition category

Condition code

Cancer

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]

Treatment: Other

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

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]

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]

Length of treatment escalation free survival (oncologist reported or obtained through medical records)

Timepoint [1]

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]

Change in % PSA post-treatment (pathological assessment at each follow-up time point)

Timepoint [2]

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]

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]

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]

Rate of SBRT related grade 3 toxicity as measured by CTCAE version 4.0 criteria.

Timepoint [4]

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?

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]

Icon Cancer Centre Richmond - Richmond

Recruitment hospital [2]

Icon Cancer Centre Epworth Freemasons - East Melbourne

Recruitment postcode(s) [1]

3121 - Richmond

Recruitment postcode(s) [2]

3002 - Melbourne

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Epworth Medical Foundation

Address [1]

89 Bridge Road, Richmond VIC 3121

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Epworth HealthCare HREC

Ethics committee address [1]

89 Bridge Road, Richmond VIC 3121

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

13/11/2013

Approval date [1]

20/02/2014

Ethics approval number [1]

622-13

Ethics committee name [2]

Monash Health HREC

Ethics committee address [2]

246 Clayton Road, Clayton VIC 3168

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

Approval date [2]

08/03/2019

Ethics approval number [2]

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

Dr Patrick Bowden

Address

Icon Cancer Centre, Level 4, 32 Erin St, Richmond VIC 3121

Country

Australia

Phone

+61399368277

Fax

[email protected]

Contact person for public queries

Name

Dr Lloyd Smyth

Address

Icon Cancer Centre, Level 1, 22 Cordelia Street, South Brisbane, QLD 4101

Country

Australia

Phone

+61 7 3737 4500

Fax

[email protected]

Contact person for scientific queries

Name

Dr Patrick Bowden

Address

Icon Cancer Centre, Level 4, 32 Erin St, Richmond VIC 3121

Country

Australia

Phone

+61399368277

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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

Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
Study results article	Yes		Bowden, P., See, A.W., Frydenberg, M., Haxhimolla,... [More Details]

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Fractionated stereotactic body radiotherapy for up to five prostate cancer oligometastases: Interim outcomes of a prospective clinical trial.	2020	https://dx.doi.org/10.1002/ijc.32509

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically