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.
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
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
Parallel
Stereotactic Body Radiotherapy (extracranial) concurrent with Immunotherapy
Other interventionRadiotherapy 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
DrugAll 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.
Overall survival
Proportion of patients alive at 6 months 1, 2, 3 and 5 years from the time of randomization
Overall progression-free survival
Proportion of patients alive and with no evidence of disease progression or new melanoma lesions as assessed by RECIST 1.1 criteria
Progression-free survival related to new lesions only
Proportion of patients alive and with no evidence of new melanoma lesions as assessed by RECIST 1.1 criteria
Overall response rate
Overall response rate from the time of randomization to the best response as assessed by RECIST 1.1
Local control of the initial oligometastases
The proportion of patients with local control of all baseline metastases: complete response, partial response or stable disease) as assessed per RECIST 1.1 criteria
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