None listed
Conditions
Brief summary
The primary purpose of this trial is to determine the maximum tolerated dose of stereotactic ablative radiotherapy (SABR) in combination with immunotherapy for the treatment of metastatic melanoma, and to determine whether the treatment has any clinical efficacy. Who is it for? You may be eligible to enroll in this trial if you are aged 18 or over and have been diagnosed with non-oligometastatic stage IV melanoma. Study details You will be participating in a phase I study. Although SABR is generally safe on its own, it is not clear how safe it is in combination with immune activating drugs. To find out we will start by giving a very low dose of SABR, which we think will be safe for almost all patients and slowly increase the dose to a level, which we think will be effective. Patients participating in this study will all receive a drug that activates their immune system and you will discuss this further with your doctor. These drugs will be delivered in a standard fashion, with at least 4 doses delivered every 3 weeks for up to 2 years or until you no longer are gaining benefit.. By participating in this study, a few days before you receive the drug you will receive SABR to one of your disease sites. You will be followed up for up to 5 years on this study It is hoped that findings from this trial will provide information on the maximum tolerated dose, and the level of efficacy of each dose level of SABR with immunotherapy for the treatment of metastatic melanoma.
Interventions
This is a prospective phase I dose-escalation study. Patients will receive a single fraction of SABR to a single site at an increasing dose and at different times while on Immunotherapy. A minimum of 3 patients will be enrolled at each increasing dose level, if safe and no grade 3 toxicities occur as assessed by the PI, the next 3 patients will be enrolled at the increased dose level until MTD is established. If these are tolerated, patients will receive SABR before each cycle, delivered to a di
This is a prospective phase I dose-escalation study. Patients will receive a single fraction of SABR to a single site at an increasing dose and at different times while on Immunotherapy. A minimum of 3 patients will be enrolled at each increasing dose level, if safe and no grade 3 toxicities occur as assessed by the PI, the next 3 patients will be enrolled at the increased dose level until MTD is established. If these are tolerated, patients will receive SABR before each cycle, delivered to a different site at the highest possible dose tolerated by that site. For SABR: All SABR treatments will be delivered in the week before up to the same day as immunotherapy Level 1: 10Gy to a single site before cycle 1 Level 2: 15Gy to a single site before cycle 1 Level 3a: 20Gy to a single site before cycle 1 Level 3b: 20Gy to a single site before cycle 2 Level 3c: 20Gy to a single site before cycle 3 Level 3d: 20Gy to a single site before cycle 4 Level 4: 24Gy to a single site before cycle 1 (peripheral lung and liver only) Level 5: 27Gy to a single site before cycle 1 (peripheral lung and liver only) Level 6: 30Gy to a single site before cycle 1 (peripheral lung and liver only) Level 7: Highest SABR dose before as many cycles as possible The PI or treatung Radiation Oncologist will decide the site to receive SABR For Immunotherapy: Patients will be treated according to Medical Oncology standard of care. Each patients treating doctor will decide which drug is most appropriate for each individual case. *Ipilimumab will consist of four cycles of 3mg/kg, delivered IV every 3 weeks until progression. *Nivoloumab will be delivered as per expanded access program, with a dose of 3mg/kg IV every two weeks for up to 96 weeks or until progression *Pembrolizumab will be delivered as per expanded access program, with a dose of 2mg/kg IV every three weeks for up to 2 years or until progression A standard 3+3 design will be used, whereby at least 3 patients are enrolled into each dose level. If no patients experience grade 3 or higher toxicity, escalation to the next level is permitted. If 1 out of 3 patients experience toxicity a further 3 patients are enrolled at that dose level and if none of these experience toxicity, escalation is permitted. If 2 of 3 or 2 of 6 patients experience toxicity, then escalation ceases and the prior dose level is defined as maximum tolerated dose.
Sponsors
Alfred Health Radiation Oncology
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
*Aged 18 or older. *Willing and able to provide informed consent. *Histologically confirmed metastatic melanoma. *At least one extra-cranial metastasis that is symptomatic or imminently symptomatic and may impact quality of life or ability to tolerate ongoing treatment. *Non-oligometastatic disease (defined more than 5 total metastasis, or more than 3 metastasis in any organ system) and 1. At least one extra-cranial metastasis that can be treated with a SABR dose of at least 20Gy (as determined by a Radiation Oncologist). 2. Intracranial disease control (defined as surgery and/or stereotactic radiotherapy to all intracranial sites). 3. At least one extra-cranial metastasis that will not be treated with SABR to monitor response. *Able to tolerate treatment with Immunotherapy (as determined by a Medical Oncologist).
Exclusion criteria
*Patient with a life expectancy less than 3 months, including those with malignant pleural or pericardial effusions. *Patients requiring immediate surgical intervention 1. Clinical or radiologic evidence of spinal cord compression 2. Dominant brain metastasis requiring surgical decompression *Pregnant or lactating females *Significant auto-immune diseases including inflammatory bowel disease, rheumatoid arthritis and Systemic Lupus Erythematosus
Outcome results
None listed