Stereotactic Ablative Radiotherapy (XRT) and Immunotherapy for Oligometastatic Extracranial Melanoma

NCT06767306 | Recruiting Phase 2 DMC

• 1 other identifier: MIA2024/508
• Study Type: interventional
• Target: 129
• Locations: 2 countries
• Sites: 5

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 fight 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.

Conditions

Melanoma Metastatic

Keywords

SABR; stereotactic body radiotherapy; Stereotactic Ablative Body Radiotherapy; SABRT; Immunotherapy; Immune Checkpoint Inhibitors; Oligometastases; Extracranial; Quality of life; Biomarkers

Outcome Measures

Primary Outcomes (1)

• Overall survival

  Proportion of patients alive at 6 months 1, 2, 3 and 5 years from the time of randomization

  5 years

Secondary Outcomes (8)

• Overall progression-free survival

  5 years

• Progression-free survival related to new lesions only

  5 years

• Overall response rate

  5 years

• Local control of the initial oligometastases

  5 years

• Safety and tolerability of each treatment arm and study procedures

  5 years

Study Arms (2)

Arm A: Concurrent stereotactic body radiotherapy + Immune checkpoint inhibitor(s)

EXPERIMENTAL

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. 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 concurrently

Arm B: Immune checkpoint inhibitor(s)

ACTIVE COMPARATOR

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.

Drug: Immunotherapy alone

Interventions

Stereotactic Body Radiotherapy (extracranial) concurrent with Immunotherapy OTHER

Radiotherapy 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. Immunotherapy 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. Other Names: Immune checkpoint inhibitor Standard of care immunotherapy First line treatment

Immunotherapy alone DRUG

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.

Also known as: Immune checkpoint inhibitor, Standard of care immunotherapy, First line treatment

Arm B: Immune checkpoint inhibitor(s)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Melanoma Institute Australia: lead

Study Sites (5)

Westmead Hospital

Westmead, New South Wales, 2145, Australia

RECRUITING

Melanoma Institute Australia

Wollstonecraft, New South Wales, 2065, Australia

RECRUITING

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

RECRUITING

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

RECRUITING

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2C4, Canada

RECRUITING

Related Publications (1)

• Hong AM, Wang T, Carlino MS, Lo SN, Menzies AM, da Silva IP, Long GV. Study protocol of a randomised phase II trial of concurrent stereotactic body radiotherapy with immunotherapy versus immunotherapy alone in patients with 1-5 extracranial melanoma oligometastases (AXIOM). BMC Cancer. 2025 Oct 21;25(1):1615. doi: 10.1186/s12885-025-15066-z.

  PMID: 41120904 DERIVED

MeSH Terms

Interventions

Radiosurgery; Immunotherapy; Immune Checkpoint Inhibitors

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Immunomodulation; Biological Therapy; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Officials

• Angela Hong

  Melanoma Institute Australia

  STUDY CHAIR

Central Study Contacts

Monica Osorio

CONTACT

+61 2 9911 7296; monica.osorio@melanoma.org.au

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open label, 2-arm parallel group, non-comparative, randomised (2:1 ratio) controlled, trial with stratification by: * Liver metastasis vs no liver metastasis * Baseline LDH: normal vs elevated * Immunotherapy agents: anti-PD-1 alone vs anti-PD-1 combination with anti-CTLA-4 or anti-LAG-3

Study Record Dates

• First Submitted: January 4, 2025
• First Posted: January 9, 2025
• Study Start: March 6, 2025
• Primary Completion (Estimated): April 1, 2033
• Study Completion (Estimated): April 1, 2033
• Last Updated: April 16, 2026

Record last verified: 2026-04

Locations

AU (4); CA (1)