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Trial registered on ANZCTR


Registration number
ACTRN12624001298505
Ethics application status
Approved
Date submitted
24/09/2024
Date registered
25/10/2024
Date last updated
25/10/2024
Date data sharing statement initially provided
25/10/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluation of Response Adapted and Anatomical Adapted Stereotactic ablative body radiotherapy (SABR) in advanced mElanoma receiving immunotherapy (ERASE phase 2 trial)
Scientific title
Evaluation of Efficacy of Response Adapted and Anatomical Adapted Stereotactic ablative body radiotherapy (SABR) in advanced mElanoma receiving immunotherapy
Secondary ID [1] 313031 0
None
Universal Trial Number (UTN)
Trial acronym
ERASE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic melanoma 335248 0
Condition category
Condition code
Cancer 331805 331805 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Up to three rounds of response-adapted and anatomically adapted SABR to up to 5 new or SABR-naïve lesions not achieving a complete metabolic response (CMR) at 3, 6 and 9 months following start of treatment with standard of care anti-programmed death (PD)-1 based immunotherapy.

Responses to immunotherapy will be based on a fluorodeoxyglucose- positron emission tomography (FDG-PET) scan. At 3 months post-initiation of immunotherapy participant's response will be used to determine whether the participant is eligible to receive SABR treatment. Participants whose lesions show a CMR at 3 months will not receive any SABR. Participants who do not achieve a CMR to immunotherapy at 3 months post-initiation of immunotherapy, with a maximum of five lesions, will be eligible for SABR treatment. At 6 and 9 months post-start of immunotherapy the participant's responses will determine whether the participant is eligible to receive further rounds of SABR treatment. Participants who were not eligible for SABR at 3 months post start of immunotherapy may proceed to SABR based on their responses at the 6- and/or 9-month follow-up timepoints. At 6 and 9 months post-start of immunotherapy if the participant has no new or worsening lesions that have previously not been treated with SABR or the participant has more than 5 new or worsening lesions that have previously not been treated with SABR then they will not be eligible for SABR. Participants not requiring SABR will serve as a non-SABR comparator group.

All participants eligible for SABR will have a radiotherapy planning session. The planning session will involve a computed tomography (CT) scan that will help the radiation oncologist to plan the treatment. Treatment for all parts of this study will be performed on the Varian Ethos™ treatment platform using local standard clinical guidelines for the delivery of stereotactic treatment for oligometastases. Participants will receive treatment in the same position and immobilised with the same stabilisation equipment used at the radiotherapy planning appointment. SABR treatment will be delivered by a radiation oncologist.

Response Adapted SABR
Taking into account the biological response to immunotherapy could avoid over-treating participants who respond well to immunotherapy and allow for higher doses for participants who don't respond as well.

Participants whose lesions show a CMR at 3 months will not receive any SABR. Participants who do not achieve a CMR to immunotherapy at 3 months post-initiation of immunotherapy, with a maximum of five lesions, will receive response-adapted SABR. The SABR dose regimen will be a minimum of 6 Gy per fraction, in 3-5 fractions, dependent on lesion size, location and biology. The SABR dose will be tailored based on the objective Positron Emission Tomography Response Criteria in Solid Tumours (PERCIST). The SABR doses used will be as below:
- For patients with partial metabolic response (PMR): 24 Gy in 3 fractions or 30 Gy in 5 fractions
- For patients with stable metabolic disease (SMD): 27 Gy in 3 fractions or 34 Gy in 5 fractions
- For patients with progressive metabolic disease or new lesions: 30 Gy in 3 fractions or 37.5 Gy in 5 fractions.

Participants with up to five new or SABR-naïve progressive lesions at 6 and/or 9 months will be eligible to receive further rounds of SABR. Participants with a CMR to immunotherapy at 3, 6 and 9 months will not receive SABR. Previously treated lesions will not receive any further SABR. A patient can receive a maximum of 3 rounds of SABR treatment based on their response to immunotherapy.

At 6 and 9 months post-start of immunotherapy if the participant has no new or worsening lesions that have not been treated with SABR before or the participant has more than 5 new or worsening lesions that have not been treated with SABR then they will not be eligible for SABR. Participants not requiring SABR will serve as a non-SABR comparator group.

Anatomically Adapted SABR
The treatment plan will undergo daily adaptation to accommodate for variations in internal anatomy from the original treatment plan (e.g. deformations and/or differences in location). By adjusting for the shape and position of the cancer the radiation dose to the important nearby organs can be minimised and higher doses of radiation can potentially be delivered. The treating radiation oncologist will have oversight of all adaptations to the treatment plan.
Intervention code [1] 329580 0
Treatment: Other
Comparator / control treatment
Standard of care (non-SABR) treatment. The standard of care for patients with advanced melanoma is upfront immunotherapy with immune checkpoint inhibitors (ICIs).

Participants will receive standard of care (no SABR) if:
- At 3 months post start of immunotherapy the participant has complete metabolic response
- At 6 and 9 months post start of immunotherapy no new or progressive SABR-naive lesions or more than 5 new or progressive SABR-naive lesions are present
Control group
Active

Outcomes
Primary outcome [1] 339444 0
12-month next line intervention free survival
Timepoint [1] 339444 0
Individual participants will be evaluated at 12 months following initiation of ICIs. Proportion of participants who have not progressed to next line intervention will be evaluated at the conclusion of the study.
Secondary outcome [1] 440015 0
Time to next line intervention
Timepoint [1] 440015 0
12 months following initiation of ICIs
Secondary outcome [2] 440016 0
12-month metabolic progression-free survival (PFS)
Timepoint [2] 440016 0
Individual participants will be evaluated at 12 months following initiation of ICIs. Proportion of participants who are free from metabolic progression will be evaluated at the conclusion of the study.
Secondary outcome [3] 440017 0
Lesions without evidence of metabolic progression
Timepoint [3] 440017 0
12 months following initiation of ICIs
Secondary outcome [4] 440018 0
Best metabolic response
Timepoint [4] 440018 0
Individual participants will be evaluated at 12 months following initiation of ICIs. Proportion of participants with best response will be evaluated at the conclusion of the study.
Secondary outcome [5] 440019 0
Objective metabolic response rate
Timepoint [5] 440019 0
6 months post SABR
Secondary outcome [6] 440020 0
Overall survival
Timepoint [6] 440020 0
End of study
Secondary outcome [7] 440021 0
Adverse events related to SABR
Timepoint [7] 440021 0
12 months following initiation of ICIs

Eligibility
Key inclusion criteria
• 18 years and over
• ECOG status 0-2
• Receiving first line PD-1 backbone immunotherapy for metastatic melanoma (including PD-1-based monotherapy or combinations with other standard (eg. anti-CTLA) or novel (eg. Relatlimab) ICIs)
• Expected to be suitable for and able to receive SABR if required (physician discretion)
• All metastases must be radiologically defined targets and be suitable for treatment with SABR in accordance with the dose fractionation options specified in the protocol.
• Patients with treated and/or asymptomatic brain metastases are eligible for inclusion. Standard of care treatment for brain metastases is permitted.
• Able to provide informed consent prior.
• Baseline FDG-PET/CT within 1 month prior to the initiation of ICIs
• No more than 5 lesions not achieving a complete metabolic response based on FDG-PET/CT at 3-months post-initiation of ICIs.
• Able to be enrolled onto the trial within 4 weeks of the 3-month FDG-PET/CT scan.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Life expectancy <6 months
• Previous adjuvant immunotherapy within 6 months prior to initiation of ICIs.
• Previous RT to any part of the body except for curative-intent skin cancer or localised prostate cancer delivered at least 2 years prior
• Persistent CTCAE grade 3 or 4 toxicity from immunotherapy at 3-months post-initiation of ICIs.
• Patients unable or unwilling to comply with protocol requirements.

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
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Data will be summarised for continuous variables as either mean and standard deviation or median and interquartile range, depending on distribution, while data for categorical variables will be summarised as frequency and percentage.

The primary outcome, 12-month next intervention free survival, will be presented as frequency and percentage. Secondary outcomes assessed categorically will be presented as frequency and percentage. Secondary outcomes assessed on an interval scale will be presented as mean and standard deviation, and where possible the change from baseline will be calculated using paired data methods. Survival at pre-defined time points (eg 12-months) will be assessed using life tables. Time-to-event outcomes will be described as median and interquartile range.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
30/09/2025
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
45
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 27145 0
Icon Cancer Centre Greenslopes - Greenslopes
Recruitment postcode(s) [1] 43223 0
4120 - Greenslopes

Funding & Sponsors
Funding source category [1] 317471 0
Commercial sector/Industry
Name [1] 317471 0
Varian Medical Systems
Country [1] 317471 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Icon Cancer Foundation
Address
Country
Australia
Secondary sponsor category [1] 319765 0
None
Name [1] 319765 0
Address [1] 319765 0
Country [1] 319765 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316188 0
Bellberry Human Research Ethics Committee H
Ethics committee address [1] 316188 0
Ethics committee country [1] 316188 0
Australia
Date submitted for ethics approval [1] 316188 0
20/02/2024
Approval date [1] 316188 0
19/06/2024
Ethics approval number [1] 316188 0

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

Contacts
Principal investigator
Name 137070 0
A/Prof Matthew Foote
Address 137070 0
Icon Cancer Centre Greenslopes Greenslopes Private Hospital Newdegate Street, Greenslopes QLD 4120
Country 137070 0
Australia
Phone 137070 0
+61 7 3737 4500
Fax 137070 0
Email 137070 0
Matthew.Foote@icon.team
Contact person for public queries
Name 137071 0
Dr Lloyd Smyth
Address 137071 0
Icon Cancer Centre, L1, 22 Cordelia Street, South Brisbane, QLD 4101
Country 137071 0
Australia
Phone 137071 0
+61 7 3737 4500
Fax 137071 0
Email 137071 0
research.iit@icon.team
Contact person for scientific queries
Name 137072 0
Dr Lloyd Smyth
Address 137072 0
Icon Cancer Centre, L1, 22 Cordelia Street, South Brisbane, QLD 4101
Country 137072 0
Australia
Phone 137072 0
+61 7 3737 4500
Fax 137072 0
Email 137072 0
research.iit@icon.team

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.