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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02374242




Registration number
NCT02374242
Ethics application status
Date submitted
9/02/2015
Date registered
27/02/2015

Titles & IDs
Public title
Anti-PD 1 Brain Collaboration for Patients With Melanoma Brain Metastases
Scientific title
A Phase II Study of Nivolumab and Nivolumab Combined With Ipilimumab in Patients With Melanoma Brain Metastases
Secondary ID [1] 0 0
ACTRN12614001315606
Secondary ID [2] 0 0
CA209-170
Universal Trial Number (UTN)
Trial acronym
ABC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma 0 0
Brain Metastases 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Nivolumab
Treatment: Drugs - Ipilimumab

Active comparator: Cohort 1 Nivolumab Monotherapy - Nivolumab 3mg/kg every 2 weeks, until disease progression, withdrawn consent, unacceptable toxicity or death.

Active comparator: Cohort 2 Nivolumab Monotherapy - Nivolumab 3mg/kg every 2 weeks, until disease progression, withdrawn consent, unacceptable toxicity or death.

Active comparator: Cohort 3 Nivolumab and Ipilimumab - Nivolumab 1mg/kg every 3 weeks x four doses and ipilimumab 3mg/kg every 3 weeks x four doses. After 12 weeks, nivolumab 3mg/kg alone every 2 weeks until disease progression, withdrawn consent, unacceptable toxicity or death.


Treatment: Drugs: Nivolumab
Nivolumab is a fully human monoclonal antibody directed against the negative immunoregulatory human cell surface receptor PD-1 (programmed death-1 or programmed cell death-1/PCD-1) with immunopotentiation activity.

Treatment: Drugs: Ipilimumab
Ipilimumab is a recombinant, human monoclonal antibody that binds to the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activation. Ipilimumab binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation. The mechanism of action of ipilimumab's effect in patients with melanoma is indirect, possibly through T-cell mediated anti-tumour immune responses.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Intracranial response rate
Timepoint [1] 0 0
Approximately 3 years
Secondary outcome [1] 0 0
Extracranial response rate
Timepoint [1] 0 0
Approximately 3 years
Secondary outcome [2] 0 0
Overall response rate
Timepoint [2] 0 0
Approximately 3 years
Secondary outcome [3] 0 0
Progression free survival in intracranial disease
Timepoint [3] 0 0
Approximately 3 years
Secondary outcome [4] 0 0
Progression free survival in extracranial disease
Timepoint [4] 0 0
Approximately 3 years
Secondary outcome [5] 0 0
Overall progression free survival
Timepoint [5] 0 0
Approximately 3 years
Secondary outcome [6] 0 0
Overall survival
Timepoint [6] 0 0
Up to approximately 5 years
Secondary outcome [7] 0 0
Safety and tolerability of nivolumab and nivolumab + ipilimumab (verse events by type, frequency and severity using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.)
Timepoint [7] 0 0
Approximately 3 years
Secondary outcome [8] 0 0
Patient rated quality of life
Timepoint [8] 0 0
Approximately 3 years
Secondary outcome [9] 0 0
Clinical response using immune related response criteria (irRC)
Timepoint [9] 0 0
Approximately 3 years
Secondary outcome [10] 0 0
Tissue and blood biomarkers of response and progression
Timepoint [10] 0 0
Approximately 3 years
Secondary outcome [11] 0 0
FET-PET response in the brain at 6 and 12 weeks on therapy (Proportion of patients with a lower standardised uptake value from baseline in intracranial metastases, following at least ONE dose of study treatment)
Timepoint [11] 0 0
Approximately 1 year

Eligibility
Key inclusion criteria
Cohort 1 and 3



1. =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 = 5mm and =40mm measurable per RECIST version 1.1 guidelines.
4. In patients with prior BRAF inhibitor treatment, intracranial disease progression must be demonstrated (RECIST >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 > 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
12. Any melanoma brain metastasis >40mm.
13. Ocular melanoma.
14. 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.
15. 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.
16. Current systemic treatment with corticosteroids, except prednisone at nonimmunosuppressive doses of = 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 intraarticular steroid injections will be permitted.
17. Any investigational drug or other systemic drug therapy for melanoma within 28 days or 5 half-lives from baseline.
18. Known to be HIV positive, or a positive test for hepatitis B and C .
19. Another malignancy or concurrent malignancy unless disease-free for 3 years.
20. Serious or unstable pre-existing medical conditions or other conditions that could interfere with the patient's safety, consent, or compliance.
21. Pregnant or breastfeeding females.
22. 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.

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 (>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 (>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 (>20% increase in SOD or new measurable brain metastases).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/11/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2028
Actual
Sample size
Target
Accrual to date
Final
76
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Melanoma Institute Australia - North Sydney
Recruitment hospital [2] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [3] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Centre - East Melbourne
Recruitment postcode(s) [1] 0 0
2060 - North Sydney
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
3002 - East Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Melanoma Institute Australia
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Melanoma and Skin Cancer Trials Limited
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
Bristol-Myers Squibb
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Georgina Long
Address 0 0
Melanoma Institute Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT02374242