Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620001229965
Ethics application status
Approved
Date submitted
29/06/2020
Date registered
17/11/2020
Date last updated
1/12/2023
Date data sharing statement initially provided
17/11/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
TiNT: Trametinib in Neurofibromatosis type 1 associated tumours
Scientific title
A phase II study of trametinib in paediatric, adolescent and young adult patients with neurofibromatosis type 1 associated plexiform neurofibromas or progressive optic pathway gliomas
Secondary ID [1] 300508 0
CTMT212A0AU01T
Secondary ID [2] 300509 0
ACCT010
Universal Trial Number (UTN)
U1111-­1221­-5556
Trial acronym
TiNT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Plexiform neurofibromatosis 316202 0
Optic pathway glioma 316203 0
Neurofibromatosis type 1 316204 0
Condition category
Condition code
Cancer 314492 314492 0 0
Children's - Brain
Cancer 314493 314493 0 0
Children's - Other
Human Genetics and Inherited Disorders 316456 316456 0 0
Other human genetics and inherited disorders
Neurological 316457 316457 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
In the main study, Cohorts 1 and 2 will all receive Trametinib intervention as follows:
Cohort 1: Neurofibromatosis Type 1 associated Plexiform Neurofibroma (NF1-PN)
Cohort 2: Neurofibromatosis Type 1 associated Optic Pathway Glioma (NF1-OPG)
Drug: Trametinib
Dose: 0.025mg/kg once daily for children 6 years and over, 0.032mg/kg once daily for children under 6.
Duration: 24 months
Mode of administration: Oral
Formulation: 0.5 or 2mg tablets; or Solution (for participants under 6 years old, or those 6 years old and over who are unable to swallow tablets).
Compliance to drug administration will be monitored by use of a participant drug diary and measurement of bottle returns.

In the sub-study, a suite of neurocognitive, quality of life and behaviour assessments and questionnaires will be evaluated in the treated Cohort 1 (NF1-PN) and Cohort 2 (NF1-OPG) and in a control group of untreated participants with Neurofibromatosis Type 1.
Intervention code [1] 316819 0
Treatment: Drugs
Comparator / control treatment
There will be no control group for the main study: tumour response, vision, safety and survival outcomes.

A control group of 60 participants will be used for the neurocognitive, behavioural and quality of life Substudy. This control group will consist of participants with NF1 and who are ineligible for the PN or OPG cohort. The control will receive no treatment and only participate in the assessments for neurocognition, behaviour and quality of life at the specified timepoints.
Control group
Active

Outcomes
Primary outcome [1] 322819 0
NF1-PN Cohort: Maximum disease response as assessed by Dombi guidelines (progressive disease, stable disease, partial response or complete response)
Timepoint [1] 322819 0
At the end of 24 months of treatment
Primary outcome [2] 322820 0
NF1-OPG Cohort: Maximum disease response as assessed using RANO Criteria (progressive disease, stable disease, minor response, partial response or complete response).
Timepoint [2] 322820 0
At the end of 24 months of treatment
Primary outcome [3] 322821 0
NF1-OPG Cohort: Change in visual acuity from baseline as measured by Teller Acuity Cards II or Amblyopia Treatment Study (ATS) HOTV crowded single optotype test, reported using the logarithm of the minimum angle of resolution (logMAR).
Timepoint [3] 322821 0
Baseline and every 3 months for 24 months after the commencement of treatment
Secondary outcome [1] 385159 0
[Primary Outcome]
NF1-PN Cohort: Absolute percentage change in tumour volume from baseline as assessed by MRI volumetric tumour measurement using Dombi guidelines.
Timepoint [1] 385159 0
At the end of 24 months of treatment
Secondary outcome [2] 385160 0
[Primary Outcome]
NF1-OPG Cohort: Estimated percentage volume change from baseline as assessed by MRI tumour measurement using RANO guidelines
Timepoint [2] 385160 0
At the end of 24 months of treatment
Secondary outcome [3] 385166 0
Global cognitive functioning: measured using either the Cognitive scale of the Bayley Scales of Infant and Toddler Development 4th edition; Full Scale IQ of the Wechsler Preschool and Primary Scale of Intelligence – fourth edition; or Full Scale IQ of the Wechsler Abbreviated Scale of Intelligence – second edition, depending on the age of the participant.
Timepoint [3] 385166 0
Baseline to 24 months. Measured from commencement of treatment in the treated cohorts and from baseline test date in the control group.
Secondary outcome [4] 385167 0
Information processing speed: measured using the Coding subtest from either the Wechsler Intelligence Scale for Children – fifth edition; or Wechsler Adult Intelligence Scale – fourth edition depending on age of the participant.
Timepoint [4] 385167 0
Baseline, 6 months, 12 months, 24 months; key comparison of interest is baseline to 24 months.
Measured from commencement of treatment in the treated cohorts and from baseline test date in the control group.
Secondary outcome [5] 385168 0
Verbal working memory: measured using the Digit Span subtests from either the Wechsler Intelligence Scale for Children – fifth edition; or Wechsler Adult Intelligence Scale – fourth edition depending on age of the participant
Timepoint [5] 385168 0
Baseline, 6 months, 12 months, 24 months; key comparison of interest is baseline to 24 months.
Measured from commencement of treatment in the treated cohorts and from baseline test date in the control group.
Secondary outcome [6] 385169 0
Psychomotor speed: measured using the Cogstate Detection Test
Timepoint [6] 385169 0
Baseline, 6 months, 12 months, 24 months; key comparison of interest is baseline to 24 months.
Measured from commencement of treatment in the treated cohorts and from baseline test date in the control group.
Secondary outcome [7] 385170 0
Attention and vigilance: measured using the Cogstate Identification Test
Timepoint [7] 385170 0
Baseline, 6 months, 12 months, 24 months; key comparison of interest is baseline to 24 months.
Measured from commencement of treatment in the treated cohorts and from baseline test date in the control group.
Secondary outcome [8] 385171 0
Visual learning: measured using the Cogstate One-Card Learning Test
Timepoint [8] 385171 0
Baseline, 6 months, 12 months, 24 months; key comparison of interest is baseline to 24 months.
Measured from commencement of treatment in the treated cohorts and from baseline test date in the control group.
Secondary outcome [9] 385172 0
Paired associate learning: measured using the Cogstate Continuous Paired Associate Learning Test
Timepoint [9] 385172 0
Baseline, 6 months, 12 months, 24 months; key comparison of interest is baseline to 24 months.
Measured from commencement of treatment in the treated cohorts and from baseline test date in the control group
Secondary outcome [10] 385173 0
Visual working memory: measured using the Cogstate One-Back Test
Timepoint [10] 385173 0
Baseline, 6 months, 12 months, and 24 months; key comparison of interest is baseline to 24 months.
Measured from commencement of treatment in the treated cohorts and from baseline test date in the control group
Secondary outcome [11] 385174 0
Verbal learning: measured using the Total correct (trials 1-5) variable from the California Verbal Learning Test-Children’s Version; or California Verbal Learning Test – 3rd edition depending on the age of the participant
Timepoint [11] 385174 0
Baseline, 6 months, 12 months, 24 months; key comparison of interest is baseline to 24 months.
Measured from commencement of treatment in the treated cohorts and from baseline test date in the control group
Secondary outcome [12] 385175 0
Inattention: measured using omission errors from the Conners Continuous Performance Test – 3rd edition; or the Conners Kiddie Continuous Performance Test – 2nd Edition depending on the age of the participant.
Timepoint [12] 385175 0
Baseline, 6 months, 12 months, 24 months; key comparison of interest is baseline to 24 months.
Measured from commencement of treatment in the treated cohorts and from baseline test date in the control group
Secondary outcome [13] 385176 0
Impulsivity: measured using the commission errors from the Conners Continuous Performance Test – 3rd edition; or the Conners Kiddie Continuous Performance Test – 2nd Edition depending on the age of the participant.
Timepoint [13] 385176 0
Baseline, 6 months, 12 months, 24 months; key comparison of interest is baseline to 24 months.
Measured from commencement of treatment in the treated cohorts and from baseline test date in the control group
Secondary outcome [14] 385177 0
Reaction Time variability: measured using the variability outcome from the Conners Continuous Performance Test – 3rd edition; or the Conners Kiddie Continuous Performance Test – 2nd Edition depending on the age of the participant.
Timepoint [14] 385177 0
Baseline, 6 months, 12 months, 24 months; key comparison of interest is baseline to 24 months.
Measured from commencement of treatment in the treated cohorts and from baseline test date in the control group
Secondary outcome [15] 385178 0
Inattentive ADHD symptoms: Measured using the Inattention content scale of the Conners 3 parent report; or the Conners Adult ADHD Rating Scale informant report, depending on the age of the participant.
Timepoint [15] 385178 0
Baseline, 6 months, 12 months, 24 months; key comparison of interest is baseline to 24 months.
Measured from commencement of treatment in the treated cohorts and from baseline test date in the control group
Secondary outcome [16] 385179 0
Hyperactive/impulsive ADHD symptoms: measured using the Hyperactivity/Impulsivity content scale of the Conners 3 parent report; or the Conners Adult ADHD Rating Scale informant report, depending on the age of the participant.
Timepoint [16] 385179 0
Baseline, 6 months, 12 months, 24 months; key comparison of interest is baseline to 24 months.
Measured from commencement of treatment in the treated cohorts and from baseline test date in the control group
Secondary outcome [17] 385180 0
Autism symptoms: measured using the Total Score of the Social Responsiveness Scale – 2nd edition, parent/informant report, depending on the age of the participant.
Timepoint [17] 385180 0
Baseline, 6 months, 12 months, 24 months; key comparison of interest is baseline to 24 months.
Measured from commencement of treatment in the treated cohorts and from baseline test date in the control group
Secondary outcome [18] 385181 0
Executive behaviours: measured using the Global Executive Composite of the Behavior Rating Inventory of Executive Function – 2nd edition (parent version); Behavior Rating Inventory of Executive Function – preschool edition (parent version); or the Behavior Rating Inventory of Executive Function – Adult edition (parent/informant report version) depending on the age of the participant.
Timepoint [18] 385181 0
Baseline, 6 months, 12 months, 24 months; key comparison of interest is baseline to 24 months.
Measured from commencement of treatment in the treated cohorts and from baseline test date in the control group
Secondary outcome [19] 385182 0
Internalising symptoms: measured using the Internalizing Problems composite summary score of the Behavioral Assessment System for Children-3rd edition, parent and self-report versions relevant to age.
Timepoint [19] 385182 0
Baseline, 6 months, 12 months, 24 months; key comparison of interest is baseline to 24 months.
Measured from commencement of treatment in the treated cohorts and from baseline test date in the control group
Secondary outcome [20] 385183 0
Adaptive skills: measured using the Adaptive Skills composite summary score (parent version) or the Personal Adjustment summary score (self-report version) of the Behavioral Assessment System for Children-3rd edition, depending on the age of the participant.
Timepoint [20] 385183 0
Baseline, 6 months, 12 months, 24 months; key comparison of interest is baseline to 24 months.
Measured from commencement of treatment in the treated cohorts and from baseline test date in the control group
Secondary outcome [21] 385186 0
Psychosocial health quality of life: measured using the Psychosocial Health Scale summary score from the PedsQL Generic Core or PedsQL Infant Scales (parent and self-report version relevant to age).
Timepoint [21] 385186 0
Baseline, 6 months, 12 months, 24 months; key comparison of interest is baseline to 24 months.
Measured from commencement of treatment in the treated cohorts and from baseline test date in the control group
Secondary outcome [22] 385187 0
Impact of a chronic health condition on family: measured using the Family Functioning Scale summary score of the PedsQL Family Impact Module (parent version only).
Timepoint [22] 385187 0
Baseline, 6 months, 12 months, 24 months; key comparison of interest is baseline to 24 months.
Measured from commencement of treatment in the treated cohorts and from baseline test date in the control group
Secondary outcome [23] 385188 0
Fatigue related quality of life: measured using the summary scores from the PedsQL Multidimensional Fatigue Scale (parent and self-report version relevant to age)
Timepoint [23] 385188 0
Baseline, 6 months, 12 months, 24 months; key comparison of interest is baseline to 24 months.
Measured from commencement of treatment in the treated cohorts and from baseline test date in the control group
Secondary outcome [24] 385189 0
Cognition related quality of life: measured using the Cognitive Functioning Scale summary score from the PedsQL Neurofibromatosis Module (parent and self-report version relevant to age).
Timepoint [24] 385189 0
Baseline, 6 months, 12 months, 24 months; key comparison of interest is baseline to 24 months.
Measured from commencement of treatment in the treated cohorts and from baseline test date in the control group
Secondary outcome [25] 385190 0
Vision related quality of life (for OPG group): measured by the Vision Scale summary score from the PedsQL Neurofibromatosis Module (parent and self-report version relevant to age)
Timepoint [25] 385190 0
Baseline, 6 months, 12 months, 24 months; key comparison of interest is baseline to 24 months.
Measured from commencement of treatment in the OPG cohort
Secondary outcome [26] 385191 0
Pain related quality of life (for PN group): measured by PEDsQL Neurofibromatosis Module Pain Scale, Pain Impact Scale and Pain Management Scale summary scores (parent and self-report version relevant to age).
Timepoint [26] 385191 0
Baseline, 6 months, 12 months, 24 months; key comparison of interest is baseline to 24 months.
Measured from commencement of treatment in the PN cohort.
Secondary outcome [27] 385192 0
Parent Distress; measured using the thermometer score from Distress Thermometer for Parents
Timepoint [27] 385192 0
Baseline, 6 months, 12 months, 24 months; key comparison of interest is baseline to 24 months.
Measured from commencement of treatment in the treated cohorts and from baseline test date in the control group
Secondary outcome [28] 385193 0
Pain Intensity of physician-selected target tumor (for PN groups only): measured using the self-report total score on the Faces Pain Scale or the Numeric Rating Scale of Pain, depending on the age of the participant
Timepoint [28] 385193 0
Baseline, 6 months, 12 months, 24 months; key comparison of interest is baseline to 24 months.
Measured from commencement of treatment in PN cohort.
Secondary outcome [29] 385194 0
Pain interference (for PN groups only): measured using the total score from the Pain Interference Index (parent and self-report relevant to age).
Timepoint [29] 385194 0
Baseline, 6 months, 12 months, 24 months; key comparison of interest is baseline to 24 months.
Measured from commencement of treatment in PN cohort.
Secondary outcome [30] 385195 0
Quality Adjusted Life Years (QALY’s): measured by the EQ-5D stable of tests (EQ-5D-5L, EQ-5D-Y), parent and self-report relevant to age of participant).
Timepoint [30] 385195 0
Baseline, 6 months, 12 months, 24 months; key comparison of interest is baseline to 24 months.
Measured from commencement of treatment in the treated cohorts and from baseline test date in the control group
Secondary outcome [31] 385282 0
[Exploratory Outcome]
Comparison of quality of life assessments with tumour measurements.
Timepoint [31] 385282 0
Baseline, 6 months, 12 months, 24 months from commencement of treatment in the treated cohorts and from baseline test date in the control group.
Secondary outcome [32] 386521 0
[Exploratory outcome]
Progression-free survival and overall survival as reported by treating clinician investigator.
Timepoint [32] 386521 0
2 years and 5 years following commencement of treatment
Secondary outcome [33] 386522 0
[Exploratory Outcome]
Adverse event reporting of skin toxicities
Timepoint [33] 386522 0
Monthly, until 28 days following completion of treatment
Secondary outcome [34] 386523 0
[Exploratory Outcome]
Adverse event reporting of all toxicities
Timepoint [34] 386523 0
Monthly, until 28 days following completion of treatment

Eligibility
Key inclusion criteria
NF1-PN and NF1-OPG Cohorts:
1. Age of patient: Patient must be between 3 months and 25 years at time of enrolment
2. Diagnosis of NF1: Patient must meet NIH criteria for NF1 or has a documented germline genetic lesion in NF1 gene predicted to be deleterious
3. PN (clinically or pathologically diagnosed) with actual or impending functional or major cosmetic deficit and surgery not deemed appropriate
or
OPG (radiologically or pathologically diagnosed) which has progressed after at least 1 line of previous chemotherapy.
4. Measurable disease:
For OPG cohort: Must have measurable target lesion/s. Measurable lesions are defined as bidimensional lesions with clearly defined margins by MRI, with two perpendicular diameters of at least 10 mm, visible on two or more axial slices. For participants with smaller lesion/s who exhibit visual loss, this inclusion criteria may be waived following discussion with the study chairs.
or
For PN cohort: Must have measurable target lesion/s amenable to volumetric MRI analysis. At least 1 target lesion must be seen on at least 3 consecutive MRI slices, and have reasonably well-defined contours in all dimensions. Minimum tumour size for measurable disease is 3 cm3. If volumetric MRI analysis not available at site, 2D analysis is permissible. Target Lesion Size must be >= 30mm in longest diameter. Most lesions >=30mm in longest diameter will have a volume greater than 3 cm3. For participants with smaller lesion/s who have significant symptoms, this inclusion criteria may be waived following discussion with the study chairs.
5. Lansky/Karnofsky performance score greater than or equal to 50 (Use Karnofsky for patients greater than 16 years of age and Lansky for patients less than or equal to 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score)
6. Life expectancy greater than 3 months
7. Haematologic function defined as:
i. Haemoglobin greater than or equal to 80 g/L
ii. Absolute Neutrophil Count greater than or equal to 1000/µL
iii. Platelet count greater than or equal to 100,000/µL
8. Adequate renal function defined as Serum creatinine normal as per institutional parameters for age and sex
9. Adequate liver function defined as:
i. Total bilirubin less than or equal to 1.5 x upper limit of normal for age
ii. AST and ALT less than or equal to 2.5 x upper limit of normal for age
10. Adequate cardiac function defined as:
i. Fractional shortening (FS) greater than or equal to 27% by echocardiogram or Ejection fraction = 53% by echocardiogram
ii. Corrected QT interval less than 460ms
11. Negative pregnancy test for women of child bearing potential (WOCBP)
12. For those of reproductive potential:
i. Agreement to use effective contraception (methods that result in less than 1% pregnancy rates) for the duration of study and 16 weeks after stopping study treatment AND
ii. Agreement not to breastfeed for the duration of study and 4 weeks after stopping study treatment
13. Provide a signed and dated informed consent form or has a legally acceptable representative capable of understanding the informed consent document and providing consent on the participant’s behalf.

Neurocognitive/Behavioural/QoL Substudy Control Group:
1. Age of patient: Patient must be between 3 months and 25 years at time of enrolment
2. Diagnosis of NF1: Patient must meet NIH criteria for NF1 or has a documented germline genetic lesion in NF1 gene predicted to be deleterious
3. Provide a signed and dated informed consent form or has a legally acceptable representative capable of understanding the informed consent document and providing consent on the participant’s behalf.
Minimum age
3 Months
Maximum age
25 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
NF1-PN and NF1-OPG Cohorts:
1. Has a known hypersensitivity to trametinib
2. Has had treatment with any other investigational or anti-neoplastic drug within 4 weeks prior to starting investigational agent
3. Treatment naïve OPG
4. OPG which has been biopsied and shown to have histology other than WHO grade 1 or 2 astrocytoma
5. PN with clinical suspicion of or histologically proven MPNST
6. Previous treatment with MEK inhibitor
7. Any concurrent anti-neoplastic therapy

Neurocognitive/Behavioural/QoL Substudy Control Group:
1. Diagnosed intracranial pathology including diagnosed head injury, CVA or hydrocephalus. OPGs allowed.
2. Significant visual or hearing problems that invalidate neurocognitive testing
3. Intellectual disability (FSIQ less than 70)
4. Insufficient English in patient or at least 1 parent to complete assessment.
5. Has had treatment with any other investigational or anti-neoplastic drug within 4 weeks
prior to starting investigational agent
6. Has had previous treatment with a MEK inhibitor.

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



Intervention assignment
Single group
Other design features
N/A
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
Descriptive statistics will be used to show trametinib efficacy separately in the PN and OPG cohorts as the number and proportion of patients who have progressed, remained stable, or demonstrated a partial or complete response. The absolute percentage change in volume from baseline to 2 years within each group (mean and 95% CI) will be described. The difference in visual acuity from baseline to 2 years will be described (mean and 95% CI) for the OPG cohort only.

For the neurocognitive, pain and QoL substudy:

Neurocognitive/behaviour: For neurocognitive function and behaviour ratings, the two treated groups will be combined. Adjusted mean differences between groups and 2-sided 95% confidence intervals at 6, 12 and 24 months will be calculated using separate linear regression models for each time point adjusted for baseline and age. The key comparison of interest for all neurocognitive and behavioural outcomes will be the between-group difference at 24 months. We will also consider whether there is a linear trend over time in neurocognitive and behavioural outcomes by fitting a linear mixed model to the data from all four time points (baseline, 6, 12, and 24 months) simultaneously. The model will include a random effect for intercept (to allow for the clustering of repeated measures) and fixed effects for group, time (e.g. study visit), group by time interaction and matching factor (age). As additional exploratory analyses, we will also repeat the above analysis including group as a 3 level variable - PN, OPG and untreated controls.
As an exploratory analysis, we will examine the association between change from baseline to 24mths in QoL and in the primary outcome for each treated group (and pain for the PN group) using Pearson’s (or Kendall’s tau for non-parametric) correlations. For distress ratings, descriptive statistics (mean, standard deviation and proportion of participants with ratings above the clinical cut-off score) will be provided for each group.

QoL: Unlike the neurocognitive outcomes, for which we expect an equivalent effect of trametinib in both treated groups, it is possible that tumour-specific factors may result in cohort-specific treatment effects on QoL outcomes for the OPG and PN groups. Thus, to determine whether it is possible to combine treated groups (PN and OPG) into a single treatment condition, or whether we should analyse PN and OPG cohorts separately, we will first conduct linear regression examining mean between-group differences (OPG vs PN) at t each time point (6, 12, 24 months) adjusted for baseline and age on the following QoL outcomes: (1) PedsQL Generic Core, Psychosocial Health Summary Score; (2) PedsQL Family Impact Module, Family Functioning Scale; (3) Peds QL Multidimensional Fatigue Scale, total summary score; (4) PedsQL NF1 Module, Cognitive QoL score; (5) Quality-adjusted life years (EQ-5D/EQ-5D-Y); and (6) Parent distress. If there is strong evidence of a difference between OPG and PN groups on a specific outcome, treated groups will be analysed separately for that outcome. If there is little evidence for between-group differences, then treated groups will be combined for that particular outcome. Regardless of whether these treated groups are combined or analysed separately, each outcome will be compared to the untreated control group. Adjusted mean differences between groups and 2-sided 95% confidence intervals at 6, 12 and 24 months will be calculated using separate linear regression models for each outcome time point adjusted for baseline and age. The key comparison of interest for all QoL outcomes will be between-group difference at 24 months. at 24 months. We will also consider whether there is a linear trend over time in the QOL outcomes and whether this trend varies by group by fitting a linear mixed model to the data from all 4 time points (baseline, 6, 12 and 24 months) simultaneously. The model will include a random effect for the intercept (to allow for the clustering of repeated measures) and fixed effects for group, time (e.g. study visit), group by time interaction, and matching factor (age).

Pain: Descriptive statistics (mean and standard deviation) will be provided for change in pain measures from baseline in the PN group only, to each time point. Only the PN cohort will be described as we are primarily interested on the effects trametinib may have on PN-related pain.

Visual QoL: Descriptive statistics (mean and standard deviation) will be provided for the change in visual QoL measure in the OPG group only, at each time point. Only the OPG cohort will be described as we are primarily interested on the effects trametinib may have on vision-related QoL as a result of treating OPGs.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/02/2021
Actual
10/03/2021
Date of last participant enrolment
Anticipated
13/12/2023
Actual
Date of last data collection
Anticipated
14/01/2028
Actual
Sample size
Target
120
Accrual to date
61
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,WA,VIC
Recruitment hospital [1] 15840 0
The Royal Childrens Hospital - Parkville
Recruitment hospital [2] 15841 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [3] 15842 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [4] 15843 0
Perth Children's Hospital - Nedlands
Recruitment hospital [5] 15844 0
Monash Children’s Hospital - Clayton
Recruitment hospital [6] 15845 0
Sydney Children's Hospital - Randwick
Recruitment hospital [7] 16936 0
John Hunter Children's Hospital - New Lambton
Recruitment hospital [8] 16937 0
Womens and Childrens Hospital - North Adelaide
Recruitment hospital [9] 17425 0
Royal Hobart Hospital - Hobart
Recruitment hospital [10] 22328 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 29290 0
2031 - Randwick
Recruitment postcode(s) [2] 29286 0
2145 - Westmead
Recruitment postcode(s) [3] 30594 0
2305 - New Lambton
Recruitment postcode(s) [4] 37489 0
3000 - Melbourne
Recruitment postcode(s) [5] 29285 0
3052 - Parkville
Recruitment postcode(s) [6] 29289 0
3168 - Clayton
Recruitment postcode(s) [7] 29287 0
4101 - South Brisbane
Recruitment postcode(s) [8] 30595 0
5006 - North Adelaide
Recruitment postcode(s) [9] 29288 0
6009 - Nedlands
Recruitment postcode(s) [10] 31153 0
7000 - Hobart
Recruitment outside Australia
Country [1] 22345 0
New Zealand
State/province [1] 22345 0
Auckland and Christchurch

Funding & Sponsors
Funding source category [1] 304925 0
Charities/Societies/Foundations
Name [1] 304925 0
Flicker of Hope Foundation Ltd
Country [1] 304925 0
Australia
Funding source category [2] 306006 0
Government body
Name [2] 306006 0
National Health and Medical Research Council.
Country [2] 306006 0
Australia
Funding source category [3] 306085 0
Charities/Societies/Foundations
Name [3] 306085 0
Wayne Francis Charitable Trust
Country [3] 306085 0
New Zealand
Primary sponsor type
Other Collaborative groups
Name
Australian and New Zealand Children's Haematology/Oncology Group
Address
ANZCHOG
Hudson Institute of Medical Research
Level 6, TRF Building
27-31 Wright St, Clayton,
Victoria 3168
Country
Australia
Secondary sponsor category [1] 305282 0
None
Name [1] 305282 0
Address [1] 305282 0
Country [1] 305282 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305333 0
The Royal Children’s Hospital Human Research Ethics Committee
Ethics committee address [1] 305333 0
Research Ethics & Governance
The Royal Children's Hospital
Level 4, South Building
50 Flemington Road
Parkville Vic 3052
Ethics committee country [1] 305333 0
Australia
Date submitted for ethics approval [1] 305333 0
10/01/2020
Approval date [1] 305333 0
13/05/2020
Ethics approval number [1] 305333 0
HREC/51826/RCHM-2020

Summary
Brief summary
The purpose of this study is to determine if a targeted therapy (a drug called trametinib) has an effect on tumour response in children, teenagers and young adults with neurofibromatosis type 1 (NF1) associated Plexiform Neurofibromas and Optic Pathway Gliomas.

Who is it for?
You may be eligible for the treatment arm of this study if you are between 3 months and 25 years old and have NF1 associated plexiform neurofibromas or progressive optic pathway gliomas. You may be eligible for the control arm of the substudy if you are between 3 months and 25 years old with NF1.

Study details
All participants in the main part of this study will receive the targeted therapy (trametinib) and are expected to take this drug daily for two years. The medication will be provided as either an oral tablet or an oral solution.

Participants taking trametinib will be expected to complete some assessments at enrolment and attend monthly hospital visits for general health reviews. Additionally, every three months for two years, assessments will include MRI scans, and cardiac and vision testing. These assessments will measure whether trametinib is effectively treating the tumour and will also monitor any side effects.

There is also a sub-study occurring within this study to find out if trametinib can improve learning, behaviour and well-being for those with NF1. For this part of the study, an untreated control group will be enrolled to compare to the trametinib-treated group described above. The untreated control group will be children, teenagers and young adults with NF1 who do not have a tumour that requires trametinib treatment. All participants in the trametinib-treated and the control groups will attend four Neuropsychology Clinic Visits over a two-year period. During these visits they will complete a number of questionnaires and tests to measure their cognitive function (thinking skills), behaviour and quality of life.

It is hoped this research will help determine if trametinib has an effect on tumours and if there are any additional impacts to cognitive function, behaviour and quality of life.
Trial website
https://anzchog.org/clinic-trails/tint-a-phase-ii-study-of-trametinib-in-paediatric-adolescent-and-young-adult-patients-with-neurofibromatosis-type-1-associated-plexiform-neurofibromas-or-progressive-optic-pathway-gliomas/
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 100034 0
Dr Andrew Dodgshun
Address 100034 0
Christchurch Hospital
2 Riccarton Avenue, Christchurch 8140, New Zealand
Country 100034 0
New Zealand
Phone 100034 0
+6433641821
Fax 100034 0
Email 100034 0
andrew.dodgshun@cdhb.health.nz
Contact person for public queries
Name 100035 0
Mrs Robyn Strong
Address 100035 0
Australian and New Zealand Children's Haematology and Oncology Group
27-31 Wright Street, Clayton, VIC 3168
Country 100035 0
Australia
Phone 100035 0
+613 8572 2684
Fax 100035 0
+613 9902 4810
Email 100035 0
anzchog_tint@anzchog.org
Contact person for scientific queries
Name 100036 0
Dr Andrew Dodgshun
Address 100036 0
Christchurch Hospital
2 Riccarton Avenue,
Christchurch 8140, New Zealand
Country 100036 0
New Zealand
Phone 100036 0
+6433641821
Fax 100036 0
Email 100036 0
andrew.dodgshun@cdhb.health.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data underlying published results only
When will data be available (start and end dates)?
Beginning 3 months following main results publication. No end date determined.
Available to whom?
Case-by-case basis at the discretion of Sponsor
Available for what types of analyses?
To achieve the aims approved by the sponsor
How or where can data be obtained?
Access subject to approvals by the Sponsor.
Principal Investigator contact: Andrew.Dodgshun@cdhb.health.nz


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIMEK inhibitors for neurofibromatosis type 1 manifestations: Clinical evidence and consensus2022https://doi.org/10.1093/neuonc/noac165
N.B. These documents automatically identified may not have been verified by the study sponsor.