Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000309482
Ethics application status
Approved
Date submitted
19/02/2025
Date registered
16/04/2025
Date last updated
16/04/2025
Date data sharing statement initially provided
16/04/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Accelerated Partial breast irradiation Using external beam Volumetric Modulated Arc Therapy (VMAT): a randomised trial of 30 Gy versus 26 Gy in five fractions investigating patient-reported outcomes.
Scientific title
Accelerated Partial breast irradiation Using external beam Volumetric Modulated Arc Therapy (VMAT): a randomised non-inferiority trial of 30 Gy versus 26 Gy in five fractions investigating patient-reported outcomes.
Secondary ID [1] 313724 0
None
Universal Trial Number (UTN)
Trial acronym
PUMA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast cancer 336325 0
Condition category
Condition code
Cancer 332864 332864 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Accelerated partial breast irradiation (APBI) will be delivered using Volumetric Modulated Arc Therapy (VMAT). Treatment will be started within 12 weeks of breast conserving surgery and within four weeks of randomisation. Treatment will occur in five (5) once-daily sessions and should be completed within seven (7) days of starting radiotherapy. Session attendance is recorded automatically in the patient electronic medical record through the treatment record and verify system. A summary of these data will be captured in the trial database in a case report form.

Arm A
Total dose of 30 Gy will be delivered in five consecutive daily fractions.

Prior to treatment patients are required to attend a treatment planning session that will assist with planning the treatment. The planning procedure will take up to approximately 60 minutes and involve a computed-tomography (CT) scan with the patient positioned in the treatment position. Treatment is expected to take around 15 minutes per treatment. The intervention will be prescribed by a radiation oncologist and administered by radiation therapists. During treatment, imaging will be completed to ensure treatment is administered accurately.

All patients will complete breast cancer related quality of life questionnaires.
Intervention code [1] 330318 0
Treatment: Other
Comparator / control treatment
The comparator for this study is another dose that is used as standard of care for APBI in Australia and globally.

Arm B
Total dose of 26 Gy will be delivered in five consecutive daily fractions. Planning and treatment procedures will be same as that for Arm A.

The aim is to determine whether quality of life is no worse when a higher dose of APBI is used compared to a slightly lower dose of APBI. The results of this study will help to guide doctors choose the best dose of APBI for patients with early breast cancer in the future.
Control group
Active

Outcomes
Primary outcome [1] 340396 0
Patient-reported breast-related cosmetic outcome,
Timepoint [1] 340396 0
36 months post randomisation
Secondary outcome [1] 443950 0
Patient-reported quality of life
Timepoint [1] 443950 0
Baseline, 8 weeks post-treatment, 6, 12, 18, 24 and 36-months post randomisation.
Secondary outcome [2] 443947 0
Patient-reported breast-related cosmetic outcome
Timepoint [2] 443947 0
Baseline, 8 weeks post-treatment, 6, 12, 18, 24 and 36-months post randomisation.
Secondary outcome [3] 443954 0
Distant disease recurrence
Timepoint [3] 443954 0
12, 24 and 36 months post-randomisation.
Secondary outcome [4] 443951 0
Ipsilateral breast tumour recurrence (IBTR)
Timepoint [4] 443951 0
12, 24 and 36 months post-randomisation.
Secondary outcome [5] 443948 0
Patient-reported breast-related functional outcome
Timepoint [5] 443948 0
Baseline, 8 weeks post-treatment, 6, 12, 18, 24 and 36-months post randomisation.
Secondary outcome [6] 443952 0
Regional Recurrence
Timepoint [6] 443952 0
12, 24 and 36 months post-randomisation.
Secondary outcome [7] 443955 0
Patterns of care for treatment of disease recurrence (IBTR, locoregional, or metastatic)
Timepoint [7] 443955 0
Upto 36 months post-randomisation
Secondary outcome [8] 443953 0
Locoregional disease recurrence
Timepoint [8] 443953 0
12, 24 and 36 months post-randomisation.
Secondary outcome [9] 443956 0
Patient satisfaction with treatment
Timepoint [9] 443956 0
At 8-weeks and 12 months post-treatment.

Eligibility
Key inclusion criteria
- Aged greater than or equal to 50 years old
- Histologically confirmed Infiltrating ductal carcinoma (IDC) or pure DCIS, less than or equal to 20mm maximum size.
- Lobular carcinoma in situ (LCIS) is permitted.
- Histologic grade I or II
- Estrogen receptor (ER) +/- progesterone receptor (PR) positive in greater than or equal to 10% of cells and HER2 receptor-negative.
- Tumour bed identifiable on imaging via surgical clips
- Clear surgical margins
- Sentinel nodes negative (at least one node taken if invasive and no isolated tumour cells)
- No evidence of distant metastasis
Minimum age
50 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- Ink on surgical margins or positive histological margins
- Lymphatic vessel invasion (LVI)
- Bilateral breast cancer
- Invasive lobular carcinoma
- Pleomorphic LCIS
- Multifocal or multicentric invasive cancer
- Invasive carcinoma with associated DCIS greater than or equal to 30mm.
- Patients receiving neoadjuvant chemotherapy, anti-HER2 agents or endocrine therapy
- Patients receiving adjuvant chemotherapy or anti-HER2 agents.
- Previous Hodgkin’s lymphoma requiring mantle radiation
- Prior radiation therapy to the ipsilateral breast
- Triple-negative breast cancer
- Documented mutation of BRCA1, BRCA2 or TP53, or at high genetic risk of breast cancer
- Known inflammatory conditions associated with higher complications after RT, such as active scleroderma, systemic lupus erythematosus (requiring steroids or immune suppressive therapy)
- Oncoplastic surgery where the primary tumour site is difficult to delineate
- No previous cancer (except BCC or SCC of the skin) unless in remission beyond five years of diagnosis
- People who are pregnant or planning to become pregnant
- People who are unable or unwilling to comply with protocol requirements.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be performed centrally by the sponsor via computer
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
One hundred sixty-eight patients are required to be recruited to this study (84 participants per arm). This target assumes a 5% rate of a moderate or worse cosmetic outcome in both the 26 Gy in 5-fraction and 30 Gy in 5-fraction arms, a 10% non-inferiority margin, 80% power, one-sided alpha of 0.025, and an attrition rate of 10%.

Data measured on an interval scale will be described using either mean and standard deviation, or median and inter-quartile range, depending on distribution, while categorical data will be described using frequency and percentage. Analysis for the primary outcome will be conducted using a generalised linear model with binomial family and identity link, with trial-group assignment included as the main effect. The effect estimate will be reported as absolute risk difference and 95% confidence interval. Secondary outcomes will similarly be conducted using generalised linear models, with family and link function chosen based on the distribution of the outcome variable (eg Gaussian family and identity link for interval data). For the primary outcome, analyses will be reported in the intention-to-treat and per-protocol samples, while for secondary outcomes the intention-to-treat sample will be used.

Sensitivity analyses will be conducted for outcomes where the outcome variable is also measured at baseline. Regression models will be re-run including the baseline value of the outcome as a covariable.

Missing data will not be imputed.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
30/06/2025
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
168
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA
Recruitment hospital [1] 27496 0
Icon Cancer Centre Windsor Gardens - Windsor Gardens
Recruitment hospital [2] 27495 0
Icon Cancer Centre Wahroonga - Wahroonga
Recruitment postcode(s) [1] 43605 0
2076 - Wahroonga
Recruitment postcode(s) [2] 43606 0
5087 - Windsor Gardens

Funding & Sponsors
Funding source category [1] 318190 0
Other
Name [1] 318190 0
Icon Cancer Foundation (ICF)
Country [1] 318190 0
Australia
Primary sponsor type
Other
Name
Integrated Clinical Oncology Network PTY Ltd (ICON)
Address
Country
Australia
Secondary sponsor category [1] 320576 0
None
Name [1] 320576 0
Address [1] 320576 0
Country [1] 320576 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316842 0
St Vincent's Hospital Melbourne Human Research Ethics Committee
Ethics committee address [1] 316842 0
Ethics committee country [1] 316842 0
Australia
Date submitted for ethics approval [1] 316842 0
23/12/2024
Approval date [1] 316842 0
27/02/2025
Ethics approval number [1] 316842 0

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

Contacts
Principal investigator
Name 139174 0
Prof John Boyages
Address 139174 0
Icon Cancer Centre Wahroonga, Sydney Adventist Hospital Level 2, Clark Tower/185 Fox Valley Rd, Wahroonga NSW 2076
Country 139174 0
Australia
Phone 139174 0
+612 9480 4200
Fax 139174 0
Email 139174 0
[email protected]
Contact person for public queries
Name 139175 0
Lloyd Smyth
Address 139175 0
Icon Cancer Centre, Level 1/22 Cordelia St, South Brisbane QLD 4101
Country 139175 0
Australia
Phone 139175 0
+61 7 3737 4500
Fax 139175 0
Email 139175 0
[email protected]
Contact person for scientific queries
Name 139176 0
John Boyages
Address 139176 0
Icon Cancer Centre Wahroonga, Sydney Adventist Hospital Level 2, Clark Tower/185 Fox Valley Rd, Wahroonga NSW 2076
Country 139176 0
Australia
Phone 139176 0
+612 9480 4200
Fax 139176 0
Email 139176 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


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.