ANZCTR - Registration

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]

CTMT212A0AU01T

Secondary ID [2]

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

Optic pathway glioma

Neurofibromatosis type 1

Condition category

Condition code

Cancer

Children's - Brain

Cancer

Children's - Other

Human Genetics and Inherited Disorders

Other human genetics and inherited disorders

Neurological

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]

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]

NF1-PN Cohort: Maximum disease response as assessed by Dombi guidelines (progressive disease, stable disease, partial response or complete response)

Timepoint [1]

At the end of 24 months of treatment

Primary outcome [2]

NF1-OPG Cohort: Maximum disease response as assessed using RANO Criteria (progressive disease, stable disease, minor response, partial response or complete response).

Timepoint [2]

At the end of 24 months of treatment

Primary outcome [3]

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]

Baseline and every 3 months for 24 months after the commencement of treatment

Secondary outcome [1]

[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]

At the end of 24 months of treatment

Secondary outcome [2]

[Primary Outcome]
NF1-OPG Cohort: Estimated percentage volume change from baseline as assessed by MRI tumour measurement using RANO guidelines

Timepoint [2]

At the end of 24 months of treatment

Secondary outcome [3]

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]

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]

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]

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]

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]

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]

Psychomotor speed: measured using the Cogstate Detection Test

Timepoint [6]

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]

Attention and vigilance: measured using the Cogstate Identification Test

Timepoint [7]

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]

Visual learning: measured using the Cogstate One-Card Learning Test

Timepoint [8]

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]

Paired associate learning: measured using the Cogstate Continuous Paired Associate Learning Test

Timepoint [9]

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]

Visual working memory: measured using the Cogstate One-Back Test

Timepoint [10]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Parent Distress; measured using the thermometer score from Distress Thermometer for Parents

Timepoint [27]

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]

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]

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]

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]

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]

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]

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]

[Exploratory Outcome]
Comparison of quality of life assessments with tumour measurements.

Timepoint [31]

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]

[Exploratory outcome]
Progression-free survival and overall survival as reported by treating clinician investigator.

Timepoint [32]

2 years and 5 years following commencement of treatment

Secondary outcome [33]

[Exploratory Outcome]
Adverse event reporting of skin toxicities

Timepoint [33]

Monthly, until 28 days following completion of treatment

Secondary outcome [34]

[Exploratory Outcome]
Adverse event reporting of all toxicities

Timepoint [34]

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

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]

The Royal Childrens Hospital - Parkville

Recruitment hospital [2]

The Children's Hospital at Westmead - Westmead

Recruitment hospital [3]

Queensland Children's Hospital - South Brisbane

Recruitment hospital [4]

Perth Children's Hospital - Nedlands

Recruitment hospital [5]

Monash Children’s Hospital - Clayton

Recruitment hospital [6]

Sydney Children's Hospital - Randwick

Recruitment hospital [7]

John Hunter Children's Hospital - New Lambton

Recruitment hospital [8]

Womens and Childrens Hospital - North Adelaide

Recruitment hospital [9]

Royal Hobart Hospital - Hobart

Recruitment hospital [10]

Peter MacCallum Cancer Centre - Melbourne

Recruitment postcode(s) [1]

3052 - Parkville

Recruitment postcode(s) [2]

2145 - Westmead

Recruitment postcode(s) [3]

4101 - South Brisbane

Recruitment postcode(s) [4]

6009 - Nedlands

Recruitment postcode(s) [5]

3168 - Clayton

Recruitment postcode(s) [6]

2031 - Randwick

Recruitment postcode(s) [7]

2305 - New Lambton

Recruitment postcode(s) [8]

5006 - North Adelaide

Recruitment postcode(s) [9]

7000 - Hobart

Recruitment postcode(s) [10]

3000 - Melbourne

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Auckland and Christchurch

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Flicker of Hope Foundation Ltd

Country [1]

Australia

Funding source category [2]

Government body

Name [2]

National Health and Medical Research Council.

Country [2]

Australia

Funding source category [3]

Charities/Societies/Foundations

Name [3]

Wayne Francis Charitable Trust

Country [3]

New Zealand

Primary sponsor type

Other Collaborative groups

Name

Australian and New Zealand Children's Haematology/Oncology Group

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

The Royal Children’s Hospital Human Research Ethics Committee

Ethics committee address [1]

Research Ethics & Governance
The Royal Children's Hospital
Level 4, South Building
50 Flemington Road
Parkville Vic 3052

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

10/01/2020

Approval date [1]

13/05/2020

Ethics approval number [1]

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/

Public notes

Contacts

Principal investigator

Name

Dr Andrew Dodgshun

Address

Christchurch Hospital
2 Riccarton Avenue, Christchurch 8140, New Zealand

Country

New Zealand

Phone

+6433641821

Email

andrew.dodgshun@cdhb.health.nz

Contact person for public queries

Name

Robyn Strong

Address

Australian and New Zealand Children's Haematology and Oncology Group
27-31 Wright Street, Clayton, VIC 3168

Country

Australia

Phone

+613 8572 2684

Email

anzchog_tint@anzchog.org

Contact person for scientific queries

Name

Andrew Dodgshun

Address

Christchurch Hospital
2 Riccarton Avenue,
Christchurch 8140, New Zealand

Country

New Zealand

Phone

+6433641821

Email

andrew.dodgshun@cdhb.health.nz

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