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Trial registered on ANZCTR


Registration number
ACTRN12624001299594
Ethics application status
Approved
Date submitted
19/08/2024
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 Stereotactic ablative body radiotherapy (SABR) in advanced mElanoma receiving immunotherapy (ERASE part 1: pilot trial)
Scientific title
Evaluation of Feasibility of Response Adapted or Response and anatomical Adapted Stereotactic ablative body radiotherapy (SABR) in advanced mElanoma receiving immunotherapy
Secondary ID [1] 311443 0
None
Universal Trial Number (UTN)
Trial acronym
ERASE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic melanoma 332731 0
Condition category
Condition code
Cancer 329451 329451 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Up to three rounds of response-adapted SABR (Pilot Part A) and response-adapted and anatomically adapted SABR (Pilot Part B) 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. The metastases must be radiologically defined targets and be suitable for treatment with SABR.

The first 5 participants will form the cohort for Pilot Part A and will be treated with response-adapted SABR if they satisfy criteria to receive SABR treatment (response criteria defined in next paragraph). If 4 of these 5 participants are successfully treated then the trial will proceed to Pilot Part B. In Pilot Part B another 5 participants will be treated with response-adapted and anatomically adapted SABR if they are eligible to receive SABR. If 4 of the 5 participants from Pilot Part B are successfully treated then the trial will progress to the ERASE Phase 2 study.

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 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.

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
Participants in both Pilots Part A and B will receive 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 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.

Anatomically Adapted SABR
In the Pilot Part B study anatomical adaptation will also be used to deliver SABR. This is achieved through daily adaptation of the treatment plan 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] 327884 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] 337266 0
Pilot A only:
Successful delivery of response adapted SABR
Timepoint [1] 337266 0
After 5 patients are treated in Pilot A
Primary outcome [2] 339045 0
Pilot B only:
Successful delivery of response adapted and anatomically adaptive SABR
Timepoint [2] 339045 0
After 5 patients are treated in Pilot B
Primary outcome [3] 339046 0
12-month next line intervention free survival
Timepoint [3] 339046 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] 431269 0
Time to next line intervention
Timepoint [1] 431269 0
12 months following initiation of ICIs
Secondary outcome [2] 431270 0
12-month metabolic progression-free survival (PFS)
Timepoint [2] 431270 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] 431271 0
Lesions without evidence of metabolic progression
Timepoint [3] 431271 0
12 months following initiation of ICIs
Secondary outcome [4] 431272 0
Best metabolic response
Timepoint [4] 431272 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] 431273 0
Objective metabolic response rate
Timepoint [5] 431273 0
6 months post SABR
Secondary outcome [6] 431274 0
Overall survival
Timepoint [6] 431274 0
End of study
Secondary outcome [7] 431275 0
Adverse events related to SABR
Timepoint [7] 431275 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
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. Outcomes for Pilots Part A and B will be presented using summary statistics.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
29/11/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
10
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 26126 0
Icon Cancer Centre Greenslopes - Greenslopes
Recruitment postcode(s) [1] 41984 0
4120 - Greenslopes

Funding & Sponsors
Funding source category [1] 315720 0
Commercial sector/Industry
Name [1] 315720 0
Varian Medical Systems
Country [1] 315720 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Icon Cancer Foundation
Address
Country
Australia
Secondary sponsor category [1] 317826 0
Commercial sector/Industry
Name [1] 317826 0
Varian Medical Systems
Address [1] 317826 0
Country [1] 317826 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314584 0
Bellberry Human Research Ethics Committee H
Ethics committee address [1] 314584 0
https://bellberry.com.au/
Ethics committee country [1] 314584 0
Australia
Date submitted for ethics approval [1] 314584 0
20/02/2024
Approval date [1] 314584 0
19/06/2024
Ethics approval number [1] 314584 0

Summary
Brief summary
Pilots Part A and B of the ERASE study aim to develop a method for using Stereotactic Ablative Radiation Therapy (SABR) that accounts for both the anatomy (the shape and position of the cancer) and the biological response to immunotherapy. These pilot studies will establish and test the planning and treatment workflow for delivering response- and anatomical-adapted SABR. Successful treatment of participants in these pilot studies will help to demonstrate that this treatment approach can be delivered.

Who is it for?
You may be eligible for this study if you are an adult receiving first line programmed death (PD)-1 backbone immunotherapy for metastatic melanoma and showing an incomplete metabolic response to this immunotherapy 3 months after commencement. You will have a maximum of 5 metastases which are not showing complete metabolic response to immunotherapy and are radiologically defined targets which are suitable for treatment with SABR.

Study details
Participants will either receive standard of care (immunotherapy with immune checkpoint inhibitors) without SABR or one to three rounds of SABR to up to 5 new or SABR-naïve lesions. Your response to immunotherapy at 3 months after commencement will help to determine whether you will receive SABR. If you do not receive SABR at 3 months you may still receive SABR at 6 and/or 9 months after commencement of immunotherapy based on your responses at those times. Lesions will only be treated once with SABR. Data on participant response to treatment and any adverse events will be collected.

It is hoped that findings from these pilot studies can support the use of response- and anatomical-adapted SABR in the treatment of metastatic melanoma and thereby minimise the radiation dose delivered to the important nearby organs, whilst potentially increasing the doses of radiation delivered to metastatic lesions. This personalised approach could avoid over-treating patients who respond well to immunotherapy and allow for higher doses for patients who don't respond as well.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 132090 0
A/Prof Matthew Foote
Address 132090 0
Icon Cancer Centre Greenslopes Greenslopes Private Hospital Newdegate Street, Greenslopes QLD 4120
Country 132090 0
Australia
Phone 132090 0
+61 7 3737 4500
Fax 132090 0
Email 132090 0
[email protected]
Contact person for public queries
Name 132091 0
Dr Lloyd Smyth
Address 132091 0
Icon Cancer Centre, Level 1, 22 Cordelia Street, South Brisbane, QLD 4101
Country 132091 0
Australia
Phone 132091 0
+61 7 3737 4500
Fax 132091 0
Email 132091 0
[email protected]
Contact person for scientific queries
Name 132092 0
Dr Lloyd Smyth
Address 132092 0
Icon Cancer Centre, Level 1, 22 Cordelia Street, South Brisbane, QLD 4101
Country 132092 0
Australia
Phone 132092 0
+61 7 3737 4500
Fax 132092 0
Email 132092 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.