A phase II study of nivolumab and nivolumab combined with ipilimumab in patients with melanoma brain metastases (ABC - Anti-PD1 Brain Collaboration Study)
- Conditions
- Cancer - BrainMelanoma Brain MetastasesMelanomaCancer - Malignant melanoma
- Registration Number
- ACTRN12614001315606
- Lead Sponsor
- Melanoma Institute Australia
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Active, not recruiting
- Sex
- All
- Target Recruitment
- 79
Cohort 1 and 3
Inclusion criteria
1. equal or greater than 18 years of age.
2. Written informed consent
3. AJCC Stage IV (any T, any N, M1c) histologically confirmed melanoma or unknown primary melanoma. Patients must have at least 1 radiological definitive brain metastasis that is equal or greater than 5mm and equal or less than 40mm measurable per RECIST version 1.1 guidelines.
4. In patients with prior BRAF inhibitor treatment, intracranial disease progression must be demonstrated (RECIST greater than 20% or new measurable brain metastases) compared with nadir of intracranial response during BRAF inhibitor treatment, and confirmed with a second MRI brain scan at any time from the beginning of the drug washout period (dabrafenib = 5 days, trametinib = 14 days).
5. No prior localised treatment for brain metastases (eg. surgery or radiotherapy).
6. Neurologically asymptomatic from brain metastases.
7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2, and life expectancy greater than 30 days.
8. Able to undergo MRI with Gadolinium contrast agent.
9. Adequate haematological, hepatic and renal organ function.
10. Women of childbearing potential: negative serum pregnancy test and effective contraception from 14 days prior to study treatment until 23 weeks after the
last dose.
11. Men with female partner of childbearing potential to use effective
contraception from 14 days prior to study treatment until 31 weeks after the last dose.
Cohort 2 - per Cohorts 1 & 3, except patients must have at least one of the following:
1. Failed prior local therapy for brain metastases (including surgery, stereotactic radiotherapy or whole brain radiotherapy) where disease has progressed per RECIST (greater than 20% increase in SOD or new measurable brain metastases),
and/or;
2. Have current neurological symptoms related to brain metastases. IF they have received prior local therapy for brain metastases, the disease must have progressed per RECIST (greater than 20% increase in SOD or new measurable brain metastases),
and/or;
3. Have leptomeningeal disease concurrently with measurable brain metastases. IF they have had failed prior local therapy for brain metastases, this must have progressed per RECIST (greater than 20% increase in SOD or new measurable brain metastases).
Exclusion criteria
1. Any melanoma brain metastasis greater than 40mm and any leptomeningeal disease, whether asymptomatic or not.
2. Ocular melanoma.
3. Prior treatment with an anti-PD-1 or anti-PD-L1 , anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
4. Patients with active, known or suspected autoimmune disease. Patients with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
5. Current systemic treatment with corticosteroids, except prednisone at nonimmunosuppressive doses of less than or equal to 10 mg/day (or equivalent). Past treatment for non-neurological symptoms allowed, if ceased 2 weeks prior to starting study
treatment. Inhaled or intranasal corticosteroids (with minimal systemic absorption) may be continued if patient on a stable dose. Non-absorbed intra-articular steroid injections will be permitted.
6. Any investigational drug or other systemic drug therapy for melanoma within 28 days or 5 half-lives from baseline.
7. Known to be HIV positive, or a positive test for hepatitis B and C.
8. Another malignancy or concurrent malignancy unless disease-free for 3 years.
9. Serious or unstable pre-existing medical conditions or other conditions that could interfere with the patient’s safety, consent, or compliance.
10. Pregnant or breastfeeding females.
11. Administration of any form of live vaccination (such as influenza vaccine) within 30 days of starting trial and anticipated use during the trial. Administration of any other vaccine is cautionary within 30 days of starting the trial and during the trial.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Proportion of patients with a complete or partial response in<br>intracranial metastases as measured using RECIST 1.1 criteria<br>(modified for brain metastases – bm RECIST), following at least ONE dose of study treatment(s).[Patients will be evaluated every 6 weeks to week 24. Thereafter assessments will be made 12 weekly until overall disease progression is documented or death.]
- Secondary Outcome Measures
Name Time Method