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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05182931


Additional trial details provided through ANZCTR are available at the end of this record.


Registration number
NCT05182931
Ethics application status
Date submitted
23/11/2021
Date registered
10/01/2022

Titles & IDs
Public title
A Prospective, Multi-Centre Trial of TKI Redifferentiation Therapy in Patients With RAIR Thyroid Cancer (I-FIRST Study)
Scientific title
A Prospective, Multi-Centre Trial of TKI Redifferentiation Therapy in Patients With RAIR Thyroid Cancer (I-FIRST Study)
Secondary ID [1] 0 0
ONJ2021-006
Universal Trial Number (UTN)
Trial acronym
I-FIRST
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Thyroid Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Thyroid
Metabolic and Endocrine 0 0 0 0
Other endocrine disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Dabrafenib 75 MG
Treatment: Drugs - Trametinib 2 MG

Experimental: BRAFv600E mutant radioiodine refractory thyroid cancer - Prior to commencing interventional treatment, participants will commence a low iodine diet and undergo thyroxine withdrawal and commence T3 replacement from day -27. On day -5 they will receive an oral dose of 124I (40MBq/1.08 mCi) with imaging at 24 hours (+/-6) post dose and a second imaging assessment within 120 hours.

Participants will receive Dabrafenib (oral, 150mg BD) and Trametinib (oral, 2mg OD) from day 1-30.

A second oral dose of I124 will be administered at day 24 followed by imaging at the same interval as baseline.

Participants achieving \>20Gy tumour uptake of I124 will be administered 6GBq (3.3Gy/GBq) 131I, I131 wb scan and SPECT/CT will be performed within 24 hours and at hospital discharge.

Participants who do not achieve \>20Gy tumour update of I-124 will move into follow up.

Follow up will occur every 12 weeks for 12 months.

Experimental: RAS mutant radioiodine refractory thyroid cancer - Prior to commencing interventional treatment, participants will commence a low iodine diet and undergo thyroxine withdrawal and commence T3 replacement from day -27. On day -5 they will receive an oral dose of 124I (40MBq/1.08 mCi) with imaging at 24 hours (+/-6) post dose and a second imaging assessment within 120 hours.

Participants will receive Trametinib (oral, 2mg OD) from day 1-30.

A second oral dose of I124 will be administered at day 24 followed by imaging at the same interval as baseline.

Participants achieving \>20Gy tumour uptake of I124 will be administered 6GBq (3.3Gy/GBq) 131I, I131 wb scan and SPECT/CT will be performed within 24 hours and at hospital discharge.

Participants who do not achieve \>20Gy tumour update of I-124 will move into follow up.

Follow up will occur every 12 weeks for 12 months.


Treatment: Drugs: Dabrafenib 75 MG
Refer arm description

Treatment: Drugs: Trametinib 2 MG
Refer arm description
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression free survival as assessed by RECIST 1.1 criteria at 6 months in participants who proceed to I131 treatment
Timepoint [1] 0 0
At 6 months following day 1.
Primary outcome [2] 0 0
Progression free survival as assessed by RECIST 1.1 criteria at 12 months in participants who proceed to I131 treatment
Timepoint [2] 0 0
At 12 months following day 1.
Secondary outcome [1] 0 0
Progression free survival as assessed by RECIST 1.1 criteria at 6 months in all participants and a control population (SELECT study)
Timepoint [1] 0 0
At 6 months following day 1.
Secondary outcome [2] 0 0
Progression free survival as assessed by RECIST 1.1 criteria at 12 months in all participants and a control population (SELECT study)
Timepoint [2] 0 0
At 12 months following day 1.
Secondary outcome [3] 0 0
Objective response rate by RECIST 1.1 criteria in all treated participants
Timepoint [3] 0 0
0-18 months or at PD
Secondary outcome [4] 0 0
Overall survival of treated participants
Timepoint [4] 0 0
From date of enrolment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years.
Secondary outcome [5] 0 0
Quantification of treatment related toxicities according to CTCAE V5.0
Timepoint [5] 0 0
From day -27 until 30 days following last dose [up to max 60 days].
Secondary outcome [6] 0 0
Quantification of radioiodine uptake in metastatic lesions before and after TKI treatment.
Timepoint [6] 0 0
From day -5 until day 30 on study.
Secondary outcome [7] 0 0
Evaluation of response to treatment by percent change from baseline of non-stimulated thyroglobulin.
Timepoint [7] 0 0
Day 0; 3, 6, 9, 12 months in participants without radiological progression.
Secondary outcome [8] 0 0
Evaluation and comparison of quality of life as measured by response to EORTC-QLQ-C30 in participants on study.
Timepoint [8] 0 0
Day -29, 1, 29; 3, 6, 9, 12 months.
Secondary outcome [9] 0 0
Evaluation and comparison of QOL as measured by response to EQ-5D-5L in participants on study.
Timepoint [9] 0 0
Day -29, 1, 29; 3, 6, 9, 12 months.
Secondary outcome [10] 0 0
Evaluation and comparison of QOL as measured by response to Kessler Psychological Distress Scale (K10) in participants on study.
Timepoint [10] 0 0
Day -29, 1, 29; 3, 6, 9, 12 months.

Eligibility
Key inclusion criteria
1. Histologically-confirmed differentiated (including poorly differentiated) thyroid cancer that is either locally advanced or metastatic.
2. Age > 18 years.
3. Life expectancy > 12 weeks.
4. Documented radiological progression by RECIST 1.1 in last 12 months.
5. Radioiodine refractory (at least one of):

1. one measurable lesion without radioiodine uptake on 131I scan,
2. at least one measurable lesion that had progressed by RECIST criteria within 12 months of 131I therapy despite 131I avidity at time of treatment, or
3. cumulative treatment with >24 GBq (600 mCi) of 131I.
6. At least one evaluable lesion as per RECIST v1.1 that has not been treated with local radiation therapy within 3 months prior to the first dose of TKI. Irradiated lesions can only be included as an evaluable lesion if it has shown radiological progression as per RECIST v1.1 on subsequent imaging following irradiation.
7. NRAS or BRAF V600E mutation tested by NGS in a NATA accredited laboratory or by recognised sequencing platform.
8. ECOG 0-1.
9. Informed consent.
10. Adequate haematological and biochemical parameters:

1. Haemoglobin = 9g/dL
2. Neutrophils = 1.5 x 109/L
3. Platelets = 100 x 109/L
4. INR = 1.4
5. Serum Creatinine = 1.3 x ULN
6. Estimated Creatinine Clearance = 30 ml/min (by Cockcroft Gault Formula)
7. Serum ALT and AST = 2.5 x ULN
8. Serum Total Bilirubin = 1.5 x ULN.
9. TSH suppression <0.1mU/L or otherwise consistent with 2015 ATA Guidelines on Thyroid Cancer
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Anaplastic thyroid cancer.
2. Suitable for curative surgery or radiotherapy.
3. Other anti-cancer (including TKI) therapy in prior 6 weeks.
4. Concurrent malignancy other than non-melanoma skin cancer. Prior malignancies treated with curative intent and no evidence of recurrence in past three years may be allowed upon discussion with the medical monitor.
5. Unstable brain metastasis. Treated or non-treated brain metastasis are allowed if neurologically stable, asymptomatic, on a stable steroid dose for a period of 2 weeks, and not anticipated to require any intervention during the trial treatment period. If treated with radiation or surgery, any related AE's should have recovered to = grade 1 prior to enrolment on trial.
6. Pregnancy, breastfeeding or unwilling to use contraception in those of child-bearing age.
7. Significant medical condition that would prevent compliance with study procedures.
8. History of retinal vein occlusion or retinopathy.
9. Iodine-containing contrast scan within 8 weeks of planned 124I scan.

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)
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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/07/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/12/2025
Actual
Sample size
Target
80
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Royal North Shore Hospital - Sydney
Recruitment hospital [2] 0 0
Royal Brisbane and Women's Hospital - Brisbane
Recruitment hospital [3] 0 0
Royal Adelaide Hsopital - Adelaide
Recruitment hospital [4] 0 0
Eastern Health - Box Hill
Recruitment hospital [5] 0 0
Monash Health - Clayton
Recruitment hospital [6] 0 0
Austin Health - Heidelberg
Recruitment hospital [7] 0 0
Alfred Hospital - Prahran
Recruitment hospital [8] 0 0
Sir Charles Gairdner Hospital - Perth
Recruitment hospital [9] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
- Sydney
Recruitment postcode(s) [2] 0 0
4029 - Brisbane
Recruitment postcode(s) [3] 0 0
- Adelaide
Recruitment postcode(s) [4] 0 0
3128 - Box Hill
Recruitment postcode(s) [5] 0 0
3168 - Clayton
Recruitment postcode(s) [6] 0 0
3084 - Heidelberg
Recruitment postcode(s) [7] 0 0
- Prahran
Recruitment postcode(s) [8] 0 0
- Perth
Recruitment postcode(s) [9] 0 0
- Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Olivia Newton-John Cancer Research Institute
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Royal North Shore Hospital
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Government body
Name [2] 0 0
Austin Health
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Sir Charles Gairdner Hospital
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Monash Health
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Peter MacCallum Cancer Centre, Australia
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Government body
Name [6] 0 0
Royal Brisbane and Women's Hospital
Address [6] 0 0
Country [6] 0 0
Other collaborator category [7] 0 0
Other
Name [7] 0 0
Eastern Health
Address [7] 0 0
Country [7] 0 0
Other collaborator category [8] 0 0
Other
Name [8] 0 0
The Alfred
Address [8] 0 0
Country [8] 0 0
Other collaborator category [9] 0 0
Other
Name [9] 0 0
Royal Adelaide Hospital
Address [9] 0 0
Country [9] 0 0

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Andrew M Scott, MD, FRACP
Address 0 0
Austin Health
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Kylie Wilkie
Address 0 0
Country 0 0
Phone 0 0
+61394963573
Fax 0 0
Email 0 0
trials@onjcri.org.au
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/NCT05182931

Additional trial details provided through ANZCTR
Accrual to date
Recruiting in Australia
Recruitment state(s)
NSW,QLD,SA,WA,VIC
Recruitment hospital [1] 69
Austin Health - Austin Hospital
Recruitment hospital [2] 70
Peter MacCallum Cancer Centre
Recruitment hospital [3] 71
Sir Charles Gairdner Hospital
Recruitment hospital [4] 72
Monash Medical Centre - Clayton campus
Recruitment hospital [5] 73
Royal Brisbane & Womens Hospital
Recruitment hospital [6] 74
Box Hill Hospital
Recruitment hospital [7] 75
The Alfred
Recruitment postcode(s) [1] 73
3084
Recruitment postcode(s) [2] 74
3000
Recruitment postcode(s) [3] 75
6009
Recruitment postcode(s) [4] 76
3168
Recruitment postcode(s) [5] 77
4029
Recruitment postcode(s) [6] 78
3128
Recruitment postcode(s) [7] 79
3004
Funding & Sponsors
Funding source category [1] 69
Government body
Name [1] 69
National Health and Medical Research Council
Address [1] 69
Canberra
Country [1] 69
Australia
Primary sponsor
Other
Primary sponsor name
Olivia Newton-John Cancer Research Institute
Primary sponsor address
L5, ONJCRWC
Austin health,
145-163 Studley Rd
Heidelberg VIC 3084
Primary sponsor country
Australia
Ethics approval
Ethics application status
Approved
Ethics committee name [1] 43
Austin Health HREC
Address [1] 43
L8 HSB 145-163 Studley Rd Heidelberg, VIC 3084
Country [1] 43
Australia
Date submitted for ethics approval [1] 43
15/10/2021
Approval date [1] 43
11/11/2021
Ethics approval number [1] 43
HREC/76249/Austin-2021
 
Public notes

Contacts
Principal investigator
Title 309 0
Prof
Name 309 0
Andrew Scott
Address 309 0
Dept MIT, L1 HSB, 145 Studley Rd
Country 309 0
Australia
Phone 309 0
0394965000
Fax 309 0
Email 309 0
andrew.scott@onjcri.org.au
Contact person for public queries
Title 310 0
Dr
Name 310 0
Jodie Palmer
Address 310 0
L5, ONJCWC, 145-163 Studley Rd
Country 310 0
Australia
Phone 310 0
0394963573
Fax 310 0
Email 310 0
trials@onjcri.org.au
Contact person for scientific queries
Title 311 0
Prof
Name 311 0
Andrew Scott
Address 311 0
Dept MIT, L1 HSB, 145 Studley Rd
Country 311 0
Australia
Phone 311 0
0394965000
Fax 311 0
Email 311 0
andrew.scott@onjcri.org.au