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Anti-PD 1 Brain Collaboration + Radiotherapy Extension (ABC-X Study)

ConditionMelanoma Stage Iv
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-120
SponsorMelanoma Institute Australia

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Female or male patients, ≥18 years of age.

Signed, written, informed consent.

AJCC Stage IV [any T, any N, M1d (0) or M1D(1)] histologically confirmed cutaneous, acral or mucosal unresectable melanoma or unknown primary melanoma and at least 1 radiological definitive brain metastasis that is ≥ 5mm and ≤40mm, measurable per RECIST version 1.1 guidelines (modified for brain metastases, enabling up to 5 target lesions in the brain as well as up to 5 extracranial target lesions). There is no upper limit restriction in the number of brain metastases, provided the remaining eligibility criteria are met.

The BRAF mutation status must be available prior to randomisation.

Disqualifiers

Patients whose intracranial disease changes between the diagnostic MRI scan and the baseline / SRS planning MRI scan and who are no longer suitable for SRS and / or require a specific alternative treatment outside of this protocol.

Melanoma brain metastasis greater than 40mm.

Evidence of leptomeningeal disease, with the exception of pathological findings seen at a previous resection of brain disease, but with no evidence of leptomeningeal disease elsewhere at the time of resection or at study entry.

History of, or current ocular melanoma (patients with mucosal and acral melanoma are eligible).

Trial design

Design model

Parallel

Treatments tested in this trial

  • Ipilimumab

    Drug

    Ipilimumab 3mg per kg every 3 weeks for 4 doses

  • Nivolumab

    Drug

    Nivolumab 1mg/kg every 3 weeks for 4 doses, then 480mg every 4 weeks.

  • Stereotactic Radiotherapy

    Radiation

    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.

  • Salvage therapy

    Other intervention

    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.

Treatment groups

218 Participants
are divided into 2 treatment groups
Group A: Nivolumab + ipilimumabActive comparator 3 interventions
Group B: Nivolumab + ipilimumab,concurrent SRSActive comparator 4 interventions

Trial outcomes

Primary outcomes

1

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

Secondary outcomes

1

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
2

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
3

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
4

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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Melanoma Institute Australia

Lead sponsor

Bristol-Myers Squibb

Collaborator

Source ClinicalTrials.gov
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