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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06767306




Registration number
NCT06767306
Ethics application status
Date submitted
4/01/2025
Date registered
9/01/2025
Date last updated
9/01/2025

Titles & IDs
Public title
Stereotactic Ablative Radiotherapy (XRT) and Immunotherapy for Oligometastatic Extracranial Melanoma
Scientific title
A Phase II, Multicentre, Non-Comparative, Randomised Controlled Trial of Stereotactic Ablative Body Radiotherapy and Immunotherapy Versus Immunotherapy Alone in Patients with Treatment Naïve Oligometastatic Extracranial Melanoma
Secondary ID [1] 0 0
MIA2024/508
Universal Trial Number (UTN)
Trial acronym
AXIOM
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Stereotactic Body Radiotherapy (extracranial) concurrent with immunotherapy
Treatment: Drugs - Immunotherapy alone

Experimental: Arm A: Concurrent stereotactic body radiotherapy + Immune checkpoint inhibitor(s) - Concurrent stereotactic body radiotherapy (SBRT) with standard of care immune checkpoint inhibitor(s) (ICI).

Patients will receive a minimum SBRT biologically effective dose (BED) of 48Gy10 to all sites of metastatic disease between cycle 1 and cycle 3 of immunotherapy. The interval between cycles 1 and 3 will depend on the prescribed immunotherapy regimen that is standard of care at each participating site.

Active comparator: Arm B: Immune checkpoint inhibitor(s) - Immunotherapy alone

Standard of care 1st line immunotherapy, as decided by the treating clinician and in accordance with the current listing on the Australian Register of Therapeutic Goods (ARTG) or applicable international regulatory agency will be administered alone.


Treatment: Other: Stereotactic Body Radiotherapy (extracranial) concurrent with immunotherapy
A minimum SBRT biologically effective dose (BED) of 48Gy10 to all sites of extracranial metastatic disease should be administered between cycle 1 and cycle 3 of standard of care immunotherapy.

Treatment: Drugs: Immunotherapy alone
All patients will receive standard of care 1st line immunotherapy as decided by the treating clinician and in accordance with the current listing on the Australian Register of Therapeutic Goods (ARTG) or applicable international regulatory agency.
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall survival
Timepoint [1] 0 0
5 years
Secondary outcome [1] 0 0
Overall progression-free survival
Timepoint [1] 0 0
5 years
Secondary outcome [2] 0 0
Progression-free survival related to new lesions only
Timepoint [2] 0 0
5 years
Secondary outcome [3] 0 0
Overall response rate
Timepoint [3] 0 0
5 years
Secondary outcome [4] 0 0
Local control of the initial oligometastases
Timepoint [4] 0 0
5 years
Secondary outcome [5] 0 0
Safety and tolerability of each treatment arm and study procedures
Timepoint [5] 0 0
5 years
Secondary outcome [6] 0 0
The requirement for immunosuppressive agents to treat adverse events
Timepoint [6] 0 0
5 years
Secondary outcome [7] 0 0
Patient reported quality of life
Timepoint [7] 0 0
5 years
Secondary outcome [8] 0 0
Salvage radiotherapy in the immunotherapy alone arm
Timepoint [8] 0 0
5 years

Eligibility
Key inclusion criteria
* Female or male patients, age 18 or older
* Willing to provide signed informed consent
* Life expectancy > 6 months
* First presentation of AJCC Stage IV (any N, M1a, M1b, M1c), histologically confirmed cutaneous, acral or unknown primary melanoma with one to five extracranial metastases detected on CT and whole body PET-CT, and considered unresectable
* A primary lesion and / or up to 4 in-transit metastases(is) (ITM) in addition to distant metastases(is) are permitted and will be counted in the maximum number of permitted baseline lesions
* Prior surgery for symptomatic disease (e.g. small bowel obstruction) for this first presentation of Stage IV melanoma is permitted, provided the total number of remaining extracranial metastases is = 5 (NOT including the resected lesion). No more than one excised metastatic lesion is permitted
* At least one metastasis should be measurable as a target lesion per RECIST version 1.1
* No evidence of cerebral metastases on MRI brain (CT brain is acceptable if there is contraindication to MRI)
* All lesions can be treated with a minimum SBRT biologically effective dose (BED) of 48Gy
* Able to tolerate treatment with immunotherapy as determined by the medical oncologist
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
* Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of randomisation
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Ocular or mucosal melanoma
* Serious or unstable medical co-morbidities or other conditions that could interfere with the patient's safety, consent, or compliance
* Patients for whom there is a definite and immediate indication for radiotherapy (e.g., spinal cord compression, rapidly progressing disease associated with clinical signs and symptoms)
* Prior radiotherapy for Stage IV disease (prior adjuvant radiotherapy to primary site or nodal field (Stage I-III disease) is permitted, however adjuvant-treated sites must not be included in the baseline lesions
* Inability to treat all disease sites with SBRT as determined by radiation oncologist
* Prior systemic drug therapy for melanoma, unless given in the neoadjuvant or adjuvant setting for Stage I-III disease
* Any contraindication to the planned standard of care immunotherapy regimen per regulatory approved product information
* For patients with liver metastases - moderate/severe liver dysfunction
* A known history of another malignancy or concurrent malignancy unless the patient is disease-free for a minimum of 1 year, is completely treated and is at low risk of recurrence
* Pregnant or breastfeeding females

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)
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

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
1/04/2025
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/04/2033
Actual
Sample size
Target
129
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Melanoma Institute Australia - Wollstonecraft
Recruitment postcode(s) [1] 0 0
2065 - Wollstonecraft

Funding & Sponsors
Primary sponsor type
Other
Name
Melanoma Institute Australia
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this research is to evaluate the addition of radiotherapy to the standard immunotherapy drugs that are given to patients with advanced or metastatic melanoma that has spread to other parts of the body. Radiotherapy uses x-rays to target and kill melanoma cells and immunotherapy works by activating the body's own immune system to seek out and ?ght melanoma cells. Both of these treatments are commonly given to patients with advanced melanoma and other cancers. Both treatments are usually given separately but can also be given together. The aim of this research is to find out if giving radiotherapy and immunotherapy together is better than giving immunotherapy alone.

The type of radiotherapy to be used in this project is known as 'stereotactic' body radiotherapy or SBRT (also known as stereotactic body ablative radiotherapy, SABR). SBRT targets the radiation very precisely at the metastatic deposits in the body. This method protects the healthy areas near the melanoma. SBRT works by delivering a high dose of radiation precisely to the areas of melanoma which causes the melanoma cells to break apart and eventually die. SBRT is given in 'fractions' which means the high dose is given in small measures over several days, depending on the number and size of metastases.
Trial website
https://clinicaltrials.gov/study/NCT06767306
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Angela Hong
Address 0 0
Melanoma Institute Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Monica Osorio
Address 0 0
Country 0 0
Phone 0 0
+61 2 9911 7296
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06767306