Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
MY TRIALS
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Register a trial
The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT03340129
Registration number
NCT03340129
Ethics application status
Date submitted
28/08/2017
Date registered
13/11/2017
Titles & IDs
Public title
Anti-PD 1 Brain Collaboration + Radiotherapy Extension (ABC-X Study)
Query!
Scientific title
A Phase II, Open Label, Randomised, Controlled Trial of Ipilimumab and Nivolumab With Concurrent Intracranial Stereotactic Radiotherapy Versus Ipilimumab and Nivolumab Alone in Patients With Melanoma Brain Metastases.
Query!
Secondary ID [1]
0
0
MIA2019/CT/258
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
ABC-X
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Melanoma Stage Iv
0
0
Query!
Condition category
Condition code
Cancer
0
0
0
0
Query!
Malignant melanoma
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Treatment: Drugs - Ipilimumab
Treatment: Drugs - Nivolumab
Treatment: Other - Stereotactic Radiotherapy
Other interventions - Salvage therapy
Active comparator: Nivolumab + ipilimumab - 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.
Active comparator: Nivolumab + ipilimumab,concurrent SRS - 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.
Treatment: Drugs: Ipilimumab
Ipilimumab 3mg per kg every 3 weeks for 4 doses
Treatment: Drugs: Nivolumab
Nivolumab 1mg/kg every 3 weeks for 4 doses, then 480mg every 4 weeks.
Treatment: Other: Stereotactic Radiotherapy
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.
Other interventions: Salvage therapy
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.
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Intervention code [2]
0
0
Treatment: Other
Query!
Intervention code [3]
0
0
Other interventions
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Neurological specific cause of death
Query!
Assessment method [1]
0
0
Proportion of patients dead at one year from randomisation and whose immediate cause of death is neurological.
Query!
Timepoint [1]
0
0
One year
Query!
Secondary outcome [1]
0
0
Intracranial response rate
Query!
Assessment method [1]
0
0
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.
Query!
Timepoint [1]
0
0
Approximately 3 years
Query!
Secondary outcome [2]
0
0
Extracranial response rate
Query!
Assessment method [2]
0
0
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.
Query!
Timepoint [2]
0
0
Approximately 5 years
Query!
Secondary outcome [3]
0
0
Overall response rate
Query!
Assessment method [3]
0
0
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 .
Query!
Timepoint [3]
0
0
Approximately 5 years
Query!
Secondary outcome [4]
0
0
Overall progression free survival
Query!
Assessment method [4]
0
0
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.
Query!
Timepoint [4]
0
0
1, 2 and 5 years
Query!
Secondary outcome [5]
0
0
Non-Neurological specific cause of death
Query!
Assessment method [5]
0
0
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.
Query!
Timepoint [5]
0
0
1 years
Query!
Secondary outcome [6]
0
0
Overall survival
Query!
Assessment method [6]
0
0
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.
Query!
Timepoint [6]
0
0
1, 2 and 5 years.
Query!
Secondary outcome [7]
0
0
Incidence of radionecrosis
Query!
Assessment method [7]
0
0
Proportion of patients with a diagnosis of radionecrosis occuring within 5 years of the start of the first course of radiotherapy.
Query!
Timepoint [7]
0
0
5 years
Query!
Secondary outcome [8]
0
0
Requirement for salvage radiotherapy
Query!
Assessment method [8]
0
0
Proportion of patients requiring salvage radiotherapy in each cohort
Query!
Timepoint [8]
0
0
1 year
Query!
Secondary outcome [9]
0
0
Requirement for salvage intracranial surgery
Query!
Assessment method [9]
0
0
Proportion of patients requiring salvage craniotomy in each cohort
Query!
Timepoint [9]
0
0
1 year
Query!
Secondary outcome [10]
0
0
Change in neurocognitive function scores
Query!
Assessment method [10]
0
0
The mean change from baseline assessment of neurocognitive function to the time of clinical response, stable disease and progression of disease.
Query!
Timepoint [10]
0
0
Approximately 5 years
Query!
Secondary outcome [11]
0
0
Description of impaired neurological function and neurological adverse events
Query!
Assessment method [11]
0
0
Description of the nature of impaired function and types of neurological adverse events.
Query!
Timepoint [11]
0
0
Approximately 5 years
Query!
Secondary outcome [12]
0
0
Time to neurological deterioration
Query!
Assessment method [12]
0
0
The time from starting immunotherapy to the time of deterioration of MoCA, CTCAE and FACT-Br.
Query!
Timepoint [12]
0
0
Approximately 5 years
Query!
Secondary outcome [13]
0
0
Duration of neurological deterioration
Query!
Assessment method [13]
0
0
The time to resolution (if any) of each functional neurocognitive deficit.
Query!
Timepoint [13]
0
0
Approximately 5 years
Query!
Secondary outcome [14]
0
0
Patient rated quality of life
Query!
Assessment method [14]
0
0
Time from starting study treatment to the time of deterioration in quality life scores and the duration of deterioration.
Query!
Timepoint [14]
0
0
Approximately 5 years
Query!
Secondary outcome [15]
0
0
Functional performance status
Query!
Assessment method [15]
0
0
Incidence of reduced functional performance by 1, 2 or 3 grades of the Eastern Cooperative Oncology Group (ECOG) performance status scale compared to baseline.
Query!
Timepoint [15]
0
0
Approximately 5 years
Query!
Secondary outcome [16]
0
0
Adverse events
Query!
Assessment method [16]
0
0
Description of all adverse events per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Query!
Timepoint [16]
0
0
Approximately 5 years
Query!
Secondary outcome [17]
0
0
Tissue, blood and gut biomarkers of response, progression and toxicity
Query!
Assessment method [17]
0
0
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.
Query!
Timepoint [17]
0
0
Approximately 5 years
Query!
Eligibility
Key inclusion criteria
1. Female or male patients, =18 years of age.
2. Signed, written, informed consent.
3. 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.
4. The BRAF mutation status must be available prior to randomisation.
5. The treating clinician(s) should consider the intracranial disease amenable to stereotactic radiotherapy over whole brain radiotherapy. Patients for whom there is a definite and immediate indication for radiotherapy (e.g. rapidly progressing disease with associated clinical signs and /or symptoms) should not be considered for enrolment.
6. Brain metastases must be untreated with any modality of radiotherapy or systemic treatment. Previous surgery for melanoma brain metastases is permitted if it resulted in gross total resection and no radiotherapeutic cavity boost was required.
7. No prior systemic treatment for brain metastases is permitted unless given in the neoadjuvant or adjuvant settings for systemic drug the treatment for extracranial disease only. At the time of neoadjuvant or adjuvant systemic therapy for extracranial disease, there should be radiological evidence of the absence of brain metastases. The presenting diagnosis of brain metastases at the time of enrolment in this study must have occurred a minimum of 6 months after stopping neoadjuvant or adjuvant systemic therapy (prior anti PD1, anti PD-L1, anti CTLA-4, BRAF / MEK inhibitors or clinical trial agents) are acceptable in the setting of neoadjuvant or adjuvant treatment
8. Asymptomatic from brain metastases at the time of study enrolment without corticosteroids, analgesia or any other treatment for the management of neurological symptoms (with the exception of antiepileptics prescribed for any reason, provided patient is asymptomatic). Resolved neurological symptoms are permitted if complete resolution, without any intervention, has been sustained for a minimum of 7 days prior to randomisation.
9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
10. A life expectancy > 30 days.
11. Able to undergo MRI with Gadolinium contrast agent. CT of the brain is not an acceptable alternative should patients be unable to safely undergo a contrast MRI.
12. Adequate haematological, hepatic and renal organ function as defined by:
1. White cell count = 2.0 × 10x9/L
2. Neutrophil count = 1.5 × 10x9/L
3. Haemoglobin = 90 g/L
4. Platelet count = 100 x 10x9/L
5. Total bilirubin = 1.5 x ULN
6. Alanine transaminase = 3.0 x ULN
7. Aspartate aminotransferase = 3.0 x ULN
8. Serum creatinine = 1.5 x the upper limit of normal (ULN). If serum creatinine is > 1.5 x ULN, calculate creatinine clearance using standard Cockcroft-Gault formula. Creatinine clearance must be 40ml/min to be eligible.
13. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first dose of study treatment and agree to use effective contraception 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:
1. Intrauterine device with a documented failure rate of less than 1% per year.
2. Vasectomised partner who is sterile prior to the female partner patient's commencement of study treatment and is the sole sexual partner for that female.
3. Combined (oestrogen and progestogen) hormonal contraception associated with inhibition of ovulation or progestogen only hormonal contraception associated with inhibition of ovulation.
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 post-menopausal (= one year without menses and >50 years of age in the absence of hormone replacement therapy).
14. Men with any female partner of childbearing potential must agree to use effective contraception from 14 days prior to commencing study treatment, throughout the treatment period and for 31 weeks* after the last dose of study treatment. Effective contraception includes:
1. Documented vasectomy and sterility
2. In the partner - intrauterine device with a documented failure rate of less than 1% per year
3. In the female partner - Combined (oestrogen and progestogen) hormonal contraception associated with inhibition of ovulation or progestogen only hormonal contraception associated with inhibition of ovulation.
* 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 and men who are sexually active with WOCBP use contraception for 5 half-lives plus 90 days.
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
120
Years
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
Exclusion Criteria
1. 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.
2. Melanoma brain metastasis greater than 40mm.
3. 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.
4. History of, or current ocular melanoma (patients with mucosal and acral melanoma are eligible).
5. Neurological symptoms from brain metastases present at baseline (resolved neurological symptoms, prior to enrolment, are permitted).
6. Prior radiotherapy to the brain (surgery permitted).
7. Prior systemic drug therapy for melanoma, unless given in the neoadjuvant or adjuvant setting and completed 6 months before enrolment in this study.
8. Patients with active, known or suspected autoimmune disease. Patients with the following are permitted to enrol:
1. Vitiligo
2. Type I diabetes mellitus
3. Residual hypothyroidism due to an autoimmune condition only requiring hormone replacement
4. Psoriasis not requiring systemic treatment
5. Autoimmune conditions not expected to recur in the absence of an external trigger.
9. Current systemic treatment with corticosteroids, or within 7 days of randomisation, with the exception of prednisone at non-immunosuppressive 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:
1. Past treatment for non-neurological symptoms allowed, if this was ceased 7 days prior to randomisation
2. Inhaled or intranasal corticosteroids (with minimal systemic absorption) may be continued if the patient is on a stable dose
3. Non-absorbed intra-articular steroid injections.
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.
10. Any active infection requiring treatment.
11. A history of interstitial lung disease.
12. Any concurrent malignancy requiring any treatment or a history of another malignancy, unless the patient has been disease-free for 3 years.
13. Serious or unstable pre-existing medical conditions or other conditions that could interfere with the patient's safety, consent, or compliance.
14. Pregnant or breastfeeding females.
15. Administration of any form of live vaccine within 30 days of starting the trial and during the trial. Administration of any other vaccine is cautionary within 30 days of starting the trial and for the duration of the treatment phase of the trial.
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 2
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Recruiting
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
14/08/2019
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
1/08/2025
Query!
Actual
Query!
Sample size
Target
218
Query!
Accrual to date
Query!
Final
Query!
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Query!
Recruitment hospital [1]
0
0
Westmead Hospital - Sydney
Query!
Recruitment hospital [2]
0
0
Calvary Mater NewcastleHospital - Waratah
Query!
Recruitment hospital [3]
0
0
Melanoma Institute Australia - Wollstonecraft
Query!
Recruitment hospital [4]
0
0
Princess Alexandra Hospital - Woolloongabba
Query!
Recruitment hospital [5]
0
0
Royal Adelaide Hospital - Adelaide
Query!
Recruitment hospital [6]
0
0
Peter MacCallum Cancer Centre - East Melbourne
Query!
Recruitment hospital [7]
0
0
Alfred Hospital - Melbourne
Query!
Recruitment postcode(s) [1]
0
0
2145 - Sydney
Query!
Recruitment postcode(s) [2]
0
0
2298 - Waratah
Query!
Recruitment postcode(s) [3]
0
0
2065 - Wollstonecraft
Query!
Recruitment postcode(s) [4]
0
0
4102 - Woolloongabba
Query!
Recruitment postcode(s) [5]
0
0
5000 - Adelaide
Query!
Recruitment postcode(s) [6]
0
0
3002 - East Melbourne
Query!
Recruitment postcode(s) [7]
0
0
3004 - Melbourne
Query!
Recruitment outside Australia
Country [1]
0
0
Norway
Query!
State/province [1]
0
0
Oslo
Query!
Funding & Sponsors
Primary sponsor type
Other
Query!
Name
Melanoma Institute Australia
Query!
Address
Query!
Country
Query!
Other collaborator category [1]
0
0
Commercial sector/industry
Query!
Name [1]
0
0
Bristol-Myers Squibb
Query!
Address [1]
0
0
Query!
Country [1]
0
0
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
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.
Query!
Trial website
https://clinicaltrials.gov/study/NCT03340129
Query!
Trial related presentations / publications
Phillips WJ, Baghai T, Ong M, Lo B, Ibrahim AM, Smith TKT, Song X. A Contemporary Report of Clinical Outcomes in Patients with Melanoma Brain Metastases. Curr Oncol. 2021 Jan 13;28(1):428-439. doi: 10.3390/curroncol28010045.
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Georgina V Long, MBBS PhD
Query!
Address
0
0
Melanoma Institute Australia
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Georgina V Long, MBBS PhD
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
+61 2 9911 7200
Query!
Fax
0
0
Query!
Email
0
0
[email protected]
Query!
Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
Query!
No/undecided IPD sharing reason/comment
Query!
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/NCT03340129