A Phase 2 interventional study of Ipilimumab and Nivolumab in Melanoma Stage Iv, sponsored by Melanoma Institute Australia. Recruiting at 9 sites in 2 countries. Open to participants aged 18 Years to 120 Years. Per ClinicalTrials.gov, last updated 2026-10-08.
Sponsored by Melanoma Institute Australia · Phase 2, Interventional, and Treatment
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Among 13 studies in Melanoma by Melanoma Institute Australia — 5 open to participants now, 9 under way, none of them phase 3. Melanoma · Melanoma Institute Australia.
Among the 13 studies in Melanoma by Melanoma Institute Australia, this one is the 3rd largest by planned enrollment of the 12 interventional ones that give a count, is the only one that started in 2019, is one of 11 in phase 2, and was the 5th registered.
3,372 studies on the registry are indexed under Melanoma; 580 are open to participants now.
Browse Melanoma studies →5 of the 13 studies in Melanoma by Melanoma Institute Australia are open now, in 7 countries. Recruiting first, the newest first:
Melanoma Institute Australia · Sites in Australia
Ages 18+
Melanoma Institute Australia · Sites in United States, Australia, Canada and 3 more countries
Ages 18+
Melanoma Institute Australia · Sites in Australia, Canada
Ages 18+
Melanoma Institute Australia · Sites in Australia
Ages 18+
By country, each count listing its studies:
Of the 468 Melanoma studies recruiting now, 381 (81%) set no upper age limit and 49 (10%) stop at 75 or younger; 47 take children under 18; 29 take healthy volunteers.
This study: 18 Years to 120 Years · all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
13 studies; the count open now beside each. This study's row is marked.
First in 2014; this study’s year is marked. 1 started in 2019.
By drug class, each counting the studies that test any of its medicines:
This study's planned enrollment of 218 is above the median of 40 across 2,650 interventional studies indexed under Melanoma.
Median enrollment 68 across the 12 interventional studies, 1,000 across the 1 observational. Of the 2 that completed or were terminated, 0 (0%) have results posted.
This tab as a report to print or save as PDF → With an account.
Melanoma Institute Australia is the lead sponsor of 16 studies on the registry; 7 are open to participants now.
2 of the studies in Melanoma by Melanoma Institute Australia that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT03340129Melanoma Institute AustraliaAnti-PD 1 Brain Collaboration + Radiotherapy Extension (ABC-X Study) | 2026-12 |
| NCT06536257Melanoma Institute AustraliaPersonalised Immunotherapy Platform | 2027-06-01 |
Add all 2 to your calendar (.ics) → With an account.
Among the 13 studies in Melanoma by Melanoma Institute Australia, from their registry updates:
This tab as a report to print or save as PDF → With an account.
This is a phase II, open label, randomised trial of ipilimumab and nivolumab with concurrent intracranial stereotactic radiotherapy versus ipilimumab and nivolumab alone in patients with asymptomatic, untreated melanoma brain metastases.
BACKGROUND The ABC study (NCT02374242) is a phase II clinical trial recruiting 3 cohorts of patients with melanoma brain metastases. 76 patients received immunotherapy with either nivolumab alone or nivolumab combined with ipilimumab. Nivolumab together with ipilimumab was shown to be more effective than nivolumab alone in melanoma brain metastases. The combination will therefore be used in this trial.
Findings from pre-clinical and clinical research provides evidence supporting the ability of radiotherapy to induce anti-tumour immune responses and augment the efficacy of anti-PD1 checkpoint blockade in melanoma and provide mechanistic rationale for combined therapy.
STUDY DESIGN This current protocol builds on the ABC study and will assess clinical, functional, toxicities and quality of life outcomes with the combined modalities of immunotherapy with radiotherapy to the brain in melanoma patients.
The main aim of this study will be to assess the effect of immunotherapy +/- concurrent stereotactic radiotherapy (SRS) on the intracranial death rate at 12 months from the commencement of treatment. Secondary aims include the RECIST response in the brain, extracranially and overall, progression free survival, overall survival, neurocognitive function, adverse event rates and quality of life.
The study will recruit 218 patients with asymptomatic, untreated melanoma brain metastases. All patients will be treated with combination ipilimumab and nivolumab at the doses and duration approved by worldwide regulatory authorities for advanced melanoma. All patients will undergo the the SRS treatment planning MRI of the brain PRIOR to randomisation to ensure that the timing of the baseline intracranial measurements are made within a similar timeframe and so that the delineation of tumour volume is accurately recorded in the same way for both cohorts. Patents will be randomised to receive concurrent intracranial SRS (within 7 days of the baseline / planning MRI scan) or immunotherapy alone. At intracranial disease progression, any form of salvage local therapy (radiotherapy or surgery) may be administered to either cohort.
Randomisation is 1:1, using a permuted, random block design with stratification by participating centre, LDH (normal / elevated), BRAF (mutant / wild type), 1-2 brain metastases versus > 2 brain metastases.
NEUROCOGNITIVE ASSESSMENT, FUNCTION AND QUALITY OF LIFE Neurocognitive impairment is a concern in the setting of radiotherapy delivered for brain metastases. The addition of immunotherapy for enhanced local disease control and survival may augment the risks. Quality of life (QoL) assessment is therefore an important objective in clinical trials studying the effects of new interventions, where side effects and tolerability are as important as clinical benefit.
Neurocognitive function will be assessed at baseline and every 6 to 12 weeks using the Montreal Cognitive Assessment (MoCA) and a neurological assessment of the patient. A member of the study team will be nominated to conduct the MoCA to allow for consistency of delivery of the examination. The MoCA measures six cognitive domains: visuospatial/executive function; naming; memory; language; abstraction; and attention. To decrease the learning effect from multiple administrations of the MoCA over a short period of time, alternate versions have been made available.
The Functional Assessment of Cancer Therapy (FACT) questionnaires are commonly used to assess cancer-related QoL issues. The FACT-Brain (FACT-Br) module provides an additional set of disease-specific questions pertaining to brain neoplasms and is completed by the patient.
Neurological assessments wil be made using the structured NANO scale at each physical examination - each neurological domain is subdivided into 3 or 4 levels of function with scores based on discrete quantifiable measures. Thus, levels of function for each domain range from 0 to 2 or 0 to 3. A score of 0 indicates normal function, while the highest score indicates the most severe level of deficit for that domain. Levels of function are distinguished by significant and measurable differences in order to avoid misinterpretation of subtle or nonspecific changes.
The EORTC QLQ-C30, an internationally validated cancer-specific QOL-instrument, assesses various facets of functioning, symptoms common in cancer patients and global QOL. The Brain Cancer Module (EORTC QLQ-BN20 is a 20-item supplement for the QLQ-C30 to assess neurological related quality of life and neurological symptoms and is being utilised in the main ABC study. Among the symptoms captured by neurocognitive tests are communication deficits and memory problems. In these cases, a patient-rated QoL tool may not capture the true effects of the disease or the intervention to treat it. Both C30 and BN20 modules have been validated for assessing health-related quality of life and symptoms in patients with brain cancer.
General health status will also be measured using the EQ-5D. The EQ-5D is a standardized instrument for use as a measure of self-reported health status. The EQ-5D comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety) and a visual analogue rating scale (VAS). The utility data generated from the EQ-5D is commonly used in cost effectiveness analyses.
CORRELATIVE BLOOD AND TISSUE BIOMARKER STUDIES Some patients may not benefit from radiation therapy and immunotherapy combinations. Therefore, biomarkers predictive of response. or the lack of it are needed. Extensive correlative analyses of tumoural and peripheral blood immunologic changes will be essential to a better understanding of the mechanistic interactions between these 2 treatment modalities. The differential composition of the gut microbiome has been shown to affect antitumor immunity and immunotherapy efficacy and will also be correlated with response and toxicity.
To address this, blood, tissue, stool and urine samples will be obtained. Blood will be collected at baseline, at 1 week of treatment and then 6 to 12 weekly to examine serum chemokines, cytokines, inflammatory markers, lymphocyte and T cell subsets and myeloid derived suppressor cells and to assess correlation with disease response or progression. All Cohorts will be included in this study.
In patients with sufficient archival melanoma tissue from metastatic sites, a baseline tumour PD-L1 level, immune markers and genetics of response and resistance will also be measured. If available, tumour tissue following progression of accessible extracranial disease and / or craniotomy will also be tested for immune and genetic markers.
Stool samples will be obtained at baseline, at weeks 6 and 12 and at the end of immunotherapy to investigate the gut microbiome composition, diversity and abundance and correlation with the response to immunotherapy and immune-related gastrointestinal toxicity. A baseline evaluation of participants' dietary habits will also be included in these analyses.
A reduction in intestinal barrier function is currently believed to play an important role in pathogenesis of many diseases, response to immunotherapy and immune related toxicity. Urinary excretion of two orally-administered non-metabolizable sugars, lactulose and mannitol, is a valuable marker for evaluating intestinal permeability. Patients will collect a urine specimen at baseline to assess this biomarker.
CONTINUED SYSTEMIC TREATMENT IN CASES OF PROGRESSIVE DISEASE
The application of traditional RECIST criteria (Response Evaluation Criteria In Solid Tumors) in patients treated with immunotherapy may lead to premature discontinuation of treatment in a patient who will eventually respond to treatment or have prolonged disease stabilization. Disease progression may occur in extracranial lesions whilst patients may continue to have disease stabilisation or response of their intracranial melanoma disease, and vice versa. The patterns of response to treatment with these immunotherapy agents differ from those with molecularly targeted agents or cytotoxic chemotherapy in several important respects:
An evaluation of data from ipilimumab phase II clinical trials in advanced melanoma found patients characterized as PD at week 12 (by WHO criteria), either by an increase in tumour burden and/or the appearance of new lesions, subsequently experienced an objective response or SD (relative to baseline) without the addition of non-ipilimumab anticancer therapy. Examination of biopsies taken from patients receiving ipilimumab demonstrated that in some small unmeasurable lesions noted at baseline, an increase in size may be interpreted as PD, when instead, this may be due to inflammation due to T cell infiltration.
There is growing evidence that patients may not need to be treated with immunotherapies indefinitely, or even for as long as the two years commonly studied in clinical trials. Rather, shorter courses of treatment may be just as effective and provide an option for retreatment should a patient progress after coming off a defined period of therapy. Patients who receive 2 years of immunotherapy have the option to cease treatment at this stage, with an option for a rechallenge of immunotherapy at the time of disease progression, if this occurs with 2 years of initial cessation.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Adequate haematological, hepatic and renal organ function as defined by:
Women of (WOCBP) must have a negative serum pregnancy test within 7 days of the first dose of study treatment and agree to use effective from 14 days prior to commencing study treatment, throughout the treatment period and for 23 weeks * after the last dose of study treatment. Effective contraception includes:
Women who are not of childbearing potential are defined as any female who has had a documented hysterectomy, bilateral oophorectomy or bilateral tubal ligation or any female who is (≥ one year without menses and >50 years of age in the absence of hormone replacement therapy).
* These durations have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that WOCBP use contraception for 5 half-lives plus 30 days.
Exclusion Criteria
Patients with active, known or suspected disease. Patients with the following are permitted to enrol:
Current systemic treatment with , or within 7 days of randomisation, with the exception of prednisone at non- doses of ≤ 10 mg/day (or equivalent, e.g. e.g. prednisone 10mg = dexamethasone 1.6mg = hydrocortisone 40mg). Patients with the following circumstances are permitted to enrol:
During the study, treatment with systemic corticosteroids is permitted during radiotherapy if the patient experiences radiation related symptoms but this should be tapered per standard clinical practice as soon as possible and before the next infusion of study drug is due. This also refers to steroids for drug related signs or symptoms.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adjuvant and neoadjuvant
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
PD-1, PD-L1 and checkpoint inhibitors
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Leptomeningeal disease
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Live vaccines
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Nivolumab 1mg/kg and ipilimumab 3mg/kg Q3W x 4 doses, then nivolumab 480 mg every 4 weeks. Any form of salvage therapy (surgery or radiotherapy) may be administered to either cohort for the treatment of intracranial disease progression.
Drug: Ipilimumab · Drug: Nivolumab · Other: Salvage therapy
Nivolumab 1mg/kg and ipilimumab 3mg/kg Q3W x 4 doses, then nivolumab 480 mg every 4 weeks. Stereotactic radiotherapy 16 to 22 Gy in 1 fraction or 24 to 30 Gy, hypofractionated for larger lesions. Stereotactic radiotherapy to commence within 7 days of of the baseline / planning MRI brain. Hypofractionated stereotactic radiotherapy should be completed within 14 day of the first fraction. Any form of salvage therapy (surgery or radiotherapy) may be administered to either cohort for the treatment of intracranial disease progression.
Drug: Ipilimumab · Drug: Nivolumab · Radiation: Stereotactic Radiotherapy · Other: Salvage therapy
Ipilimumab 3mg per kg every 3 weeks for 4 doses
Also known as: Yervoy
Nivolumab 1mg/kg every 3 weeks for 4 doses, then 480mg every 4 weeks.
Also known as: Opdivo
The first dose of immunotherapy Must be given prior to the start of radiotherapy. One fraction at between 16 to 22 Gy or 24 to 30 Gy hypofractionated for larger lesions.
Any form of salvage therapy (surgery or radiotherapy) for intracranial disease progression, further disease control at any site, symptom control or treatment of cerebral haemorrhage or cerebral radionecrosis.
Neurological specific cause of death
Proportion of patients dead at one year from randomisation and whose immediate cause of death is neurological.
Time frame: One year
Intracranial response rate
The best response in intracranial metastases as measured using brain modified (bm) RECIST, following at least ONE dose of nivolumab and ipilimumab and based on imaging from week 6 onwards and confirmed a minimum of 4 weeks later.
Time frame: Up to 10 years
Extracranial response rate
The best response in extracranial disease for each patient measured using bm RECIST, following at least ONE dose of nivolumab and ipilimumab and based on imaging from week 12 onwards.
Time frame: Approximately 10 years
Overall response rate
Proportion of patients with an overall complete or partial response as measured using bm RECIST following at least ONE dose of nivolumab and ipilimumab and based on imaging from week 12 onwards .
Time frame: Up to 10 years
Overall progression free survival
Time from the start of study treatment to the date of any progression of disease as measured using bm RECIST and based on imaging from week 12 onwards.
Time frame: 1, 2, 5 and 10 years
Non-Neurological specific cause of death
Proportion of patients dead at one year from randomisation and whose immediate cause of death was due to melanoma but from causes other than brain metastases.
Time frame: Up to 10 years
Overall survival
Time from commencing study treatment to the date of death from any cause. Patients still alive at the end of the study will be censored at the date of their last assessment.
Time frame: 1, 2, 5 and 10 years.
Incidence of radionecrosis
Proportion of patients with a diagnosis of radionecrosis occuring within 5 years of the start of the first course of radiotherapy.
Time frame: 5 years
Requirement for salvage radiotherapy
Proportion of patients requiring salvage radiotherapy in each cohort
Time frame: 1 year
Requirement for salvage intracranial surgery
Proportion of patients requiring salvage craniotomy in each cohort
Time frame: 1 year
Change in neurocognitive function scores
The mean change from baseline assessment of neurocognitive function to the time of clinical response, stable disease and progression of disease.
Time frame: Up to 10 years
Description of impaired neurological function and neurological adverse events
Description of the nature of impaired function and types of neurological adverse events.
Time frame: Up to 10 years
Time to neurological deterioration
The time from starting immunotherapy to the time of deterioration of MoCA, CTCAE and FACT-Br.
Time frame: Up to 10 years
Duration of neurological deterioration
The time to resolution (if any) of each functional neurocognitive deficit.
Time frame: Up to 10 years
Patient rated quality of life
Time from starting study treatment to the time of deterioration in quality life scores and the duration of deterioration.
Time frame: Up to 10 years
Functional performance status
Incidence of reduced functional performance by 1, 2 or 3 grades of the Eastern Cooperative Oncology Group (ECOG) performance status scale compared to baseline.
Time frame: Up to 10 years
Adverse events
Description of all adverse events per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Time frame: Up to 10 years
Tissue, blood and gut biomarkers of response, progression and toxicity
Correlation of the baseline PD-L1 status, immune markers, genomics and other biomarkers in tumour tissue and blood and the composition and diversity of the gut microbiome with RECIST response and toxicity. Correlation of gastrointestinal mucosal integrity with bacterial composition in stool samples, RECIST response and immune related adverse events.
Time frame: Up to 10 years
Not enrolling at this site.
Plan to share: No
Started Aug 2019 (actual). Primary completion is estimated for Dec 2026, 88 months after the start.
Of 278 non-industry phase 2 interventional studies under Melanoma, half reached primary completion within 67 months of starting (the median), counting those still running; a quarter within 41 and three quarters within 94. This study's planned 88 months is above that.
Counting every sponsor, half of 384 studies reached it within 53 months; a quarter within 32 and three quarters within 90.
Primary completion moved once since we started tracking on Sep 25, 2026: Aug 2026 → Dec 2026, on Oct 8, 2026.
Earlier changes are on the record history on ClinicalTrials.gov ↗
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Melanoma Institute Australia