None listed
Conditions
Brief summary
This study is examining the safety and biological effects of combining Ipilimumab and radiotherapy, or combining Ipilimmab, Nivolumab and radiotherapy in patients with metastatic melanoma. Who is it for? You may be eligible to join this study if you are aged over 18 years and have been diagnosed with advanced melanoma stage IIIc or IV. Trial details 6 participants in this trial will undergo 5 daily doses of radiotherapy during week 1. They will also receive Ipilimumab at a dose of either 3mg/kg or 10mg/kg at weeks 1, 4, 7, and 10. This drug will be administered intravenously (i.e. directly into the vein) over a period of 90 minutes. 24 patients in this trial will undergo 5 daily doses of radiotherapy during week 1. They will also receive Nivolumab at a dose of 1,g/kg together with Ipilimumab at a dose of 3mg/kg at weeks 1, 4, 7 and 10. This group will also receive Nivolumab 3mg/kg every 2 weeks after as maintenance. These drugs will be administered intravenously (i.e directly into the vein). Participants will be reviewed for up to 24 months in order to determine treatment toxicities, tumour response, and immune response.
Interventions
Cohort 1 (6 patients) This group involves giving 25 Gy of radiotherapy in 5 daily fractions during the first week. Ipilimumab 3mg/kg will be given intravenously commencing on day 1 of radiotherapy and will be administered weeks 1, 4, 7, and 10, for a total of 4 infusions.
Cohort 2 (subsequent 24 patients) This group involves giving 25 Gy of radiotherapy in 5 daily fractions during the first week. Ipilimumab 3mg/kg with Nivolumab 1mg/kg will be given intravenously commencing on day 1 of radiother
Cohort 1 (6 patients) This group involves giving 25 Gy of radiotherapy in 5 daily fractions during the first week. Ipilimumab 3mg/kg will be given intravenously commencing on day 1 of radiotherapy and will be administered weeks 1, 4, 7, and 10, for a total of 4 infusions. Cohort 2 (subsequent 24 patients) This group involves giving 25 Gy of radiotherapy in 5 daily fractions during the first week. Ipilimumab 3mg/kg with Nivolumab 1mg/kg will be given intravenously commencing on day 1 of radiotherapy and will be administered weeks 1, 4, 7, and 10, for a total of 4 infusions. This will be followed by maintenance Nivolumab 3mg/kg every 2 weeks indefinitely until disease progression or unacceptable tolerance.
Sponsors
Peter MacCallum Cancer Centre
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
1.Voluntarily signed and dated institutional ethics committee (IEC) approved informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before performing protocol-related procedures that are not part of standard patient care. 2.Able to comply with visits/procedures required by the protocol 3.Life expectancy of at least 3 months 4.> 18 years of age 5.Good performance status (ECOG 0-1) 6.Histologically proven advanced melanoma stage IIIC or IV 7.Measurable disease by modified RECIST 1.1 criteria (irradiated index lesion not included in overall response assessment). 8.Index lesion to be irradiated is measurable by RECIST 1.1 criteria 9.Index lesion to be irradiated is amenable to biopsy 10.Adequate hematologic, renal and liver function 11.Women of childbearing potential (WOCBP) and men must be using an acceptable method of contraception (using the clinicians’ discretion) to avoid pregnancy throughout the study and for up to 12 weeks after the last dose in such a manner that the risk of pregnancy is minimized.
Exclusion criteria
1.Symptomatic brain metastases or those treated < 3 months previously 2.Patients requiring RT to brain, or chest and abdomen where it is expected that viscera will be in field 3.Patients being recommended a higher dose of RT (e.g. 30Gy/10#) 4.Taking immunosuppressive doses of corticosteroids (>5mg of prednisolone or equivalent) or other immunosuppressant medications 5.Previous treatment with Ipilimumab, nivolumab or Pembrolizumab 6.Previous other investigational products within last 4 weeks 7.Uncontrolled infectious diseases (HIV, Hepatitis B etc) 8.Autoimmune disease (including, but not limited to Crohn’s Disease, Ulcerative Colitis, Rheumatoid Arthritis etc) 9.Prior malignancy active within the previous 3 years, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast 10. Prior allogenic stem cell transplant 11. History of immunodeficiency
Outcome results
None listed