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Trial registered on ANZCTR


Registration number
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ACTRN12626001327370
Ethics application status
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Approved
Date submitted
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18/09/2026
Date registered
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4/11/2026
Date last updated
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4/11/2026
Date data sharing statement initially provided
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4/11/2026
Type of registration
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Retrospectively registered

Titles & IDs
Public title
A rapid assessment and treatment pathway using targeted therapy and immunotherapy for people with anaplastic thyroid cancer
Scientific title
ACTIvate: The Anaplastic Cancer of the Thyroid Immunotherapy Trial: A prospective, open-label pilot trial of a rapid multidisciplinary assessment pathway (RADAR) with molecular profiling-guided targeted therapy and/or immunotherapy to assess progression-free survival in patients with anaplastic thyroid cancer
Additional trial identifiers [1] 318482 0
Nil
Universal Trial Number (UTN)
Trial acronym
ACTIvate
Related trial records

Health condition
Health condition(s) studied:
Anaplastic Thyroid Cancer 343658 0
Condition category
Condition code
Cancer 339769 339769 0 0
Thyroid

Intervention/exposure
Study type
Interventional
Description of the intervention or exposure
Drug treatments are not supplied, funded or allocated by this trial. No trial funding is available for study drugs. All agents named below are TGA-registered but not all are PBS-subsidised for anaplastic thyroid cancer. Where a participant and their treating team elect to pursue one of these treatments, access is sought for that individual through an Individual Patient Use (IPU) application at Royal North Shore Hospital, compassionate or sponsored access programs, local health district subsidy where available, or self-funding. Drugs are prescribed and administered as clinical care by the treating clinicians at Royal North Shore Hospital, and receipt of any treatment is contingent on the agent being obtainable within a clinically useful timeframe. Where a recommended agent cannot be accessed, the participant receives the best available treatment as determined by the RADAR multidisciplinary team in accordance with current best practice and published guidelines, and remains in the trial with outcomes recorded.

The intervention delivered by the study team is the RADAR pathway (Rapid Access for Diagnosis, Assessment, and Response), received by all participants. RADAR is a rapid multidisciplinary assessment and coordination pathway delivered in the following steps.

Step 1 — Referral (day 0). A participant with a diagnosis of, or clinical suspicion of, anaplastic thyroid cancer is referred to the RADAR team. A designated surgical registrar coordinates the response and convenes the team.

Step 2 — Assessments performed before the team convenes. Where not already available at referral, the following are undertaken in parallel with convening the team: clinical evaluation including assessment of vocal cord function; blood tests (full blood count, electrolytes including creatinine, calcium, magnesium and phosphate, liver function tests, thyroid stimulating hormone, free thyroxine, thyroglobulin and anti-thyroglobulin antibodies); neck ultrasound; and contrast CT of head, neck, mediastinum, chest, abdomen and pelvis. Where a participant has already undergone diagnostic biopsy before referral, that material is used and Step 4 is not repeated.

Step 3 — Multidisciplinary team meeting, within 24 hours of referral on weekdays or within 48 hours on weekends. The team convenes to review available clinical and imaging data, confirm the diagnostic plan, and determine initial management. The team includes endocrinologists, medical oncologists, endocrine surgeons, anatomical pathologists, radiation oncologists and palliative care physicians, attending as clinically indicated.

Step 4 — Tissue diagnosis, performed after the team convenes, within 24 hours of the meeting. Image-guided core needle biopsy, preferred over fine needle aspiration.

Step 5 — Molecular profiling, performed after biopsy. Mutation-specific immunohistochemistry for BRAF V600E, result within 24 hours of the first H&E-stained slide. Next-generation sequencing for BRAF V600E, RAS Q61R, and ALK, RET/PTC and NTRK rearrangements, result within 7 days, performed on the Genexus platform at the Cancer Genetics Laboratory, Kolling Institute. PD-L1 status and tumour mismatch repair deficiency are also assessed.

Step 6 — Baseline functional imaging, performed after the team convenes. Whole-body 18F-FDG PET/CT and whole-body PD-L1 PET/CT.

Step 7 — Treatment recommendation. Following molecular profiling, the team issues a treatment recommendation based on mutation status together with assessment of resectability and fitness for active treatment.

Frequency of review. Each participant receives an initial RADAR review at referral, as above. Participants then receive ongoing RADAR multidisciplinary review approximately monthly while on active treatment, including review of interval imaging to determine timing of surgery where neoadjuvant treatment has been recommended, and additional reviews at any point of clinical change, disease progression, or decision regarding change of treatment.

Time to treatment commencement. Treatment is commenced as soon as the relevant result is available and the agent is obtainable. Where mutation-specific immunohistochemistry is determinative, this is anticipated within approximately 2 to 3 days of entry to the RADAR pathway; where next-generation sequencing is required, within approximately 7 to 10 days. Commencement of drug treatment is additionally contingent on drug access, as described above.

Overall duration. Each participant is followed for 6 months from registration for the primary outcome, with follow-up continuing to 12 months for exploratory outcomes. The RADAR pathway is delivered to each participant from referral until the end of active treatment or transition to best supportive care. Recruitment is over 18 to 24 months, and the overall study duration is approximately 36 months from first participant enrolment to final data collection.

RADAR is delivered to every participant irrespective of drug availability.

Treatment recommendations issued at RADAR. RADAR generates a treatment recommendation based on molecular profiling together with multidisciplinary assessment of resectability and fitness for active treatment. There is no randomisation. Recommendations are as follows.

BRAF V600E-mutant disease (anticipated approximately 25% of participants). Dabrafenib, 150 mg twice daily, oral capsules, plus trametinib, 2 mg once daily, oral tablet, plus pembrolizumab, 200 mg every 3 weeks, intravenous infusion. Recommended duration 4–8 weeks in the neoadjuvant setting, with CT imaging every 4 weeks to assess response and timing of surgery, targeted therapy withdrawn 1 week before surgery, surgical resection of residual disease where the multidisciplinary team judges the disease resectable, and consideration of recommencing tyrosine kinase inhibitors 2–3 weeks post-operatively with optional adjuvant radiotherapy and continued immunotherapy. Continuation to 6 months or until progression, unacceptable toxicity or withdrawal.

No targetable molecular alteration identified. Lenvatinib, 24 mg once daily, oral capsules, plus pembrolizumab, 200 mg every 3 weeks, intravenous infusion, with or without radiotherapy and with or without surgery depending on multidisciplinary assessment of resectability. Continuation to 6 months or until progression, unacceptable toxicity or withdrawal.

RET/PTC rearrangement. Selpercatinib, 160 mg twice daily, oral capsules, plus pembrolizumab, 200 mg every 3 weeks, intravenous infusion, with or without radiotherapy. Continuation to 6 months or until progression, unacceptable toxicity or withdrawal.

NTRK rearrangement. Larotrectinib, 100 mg twice daily, oral capsules, plus pembrolizumab, 200 mg every 3 weeks, intravenous infusion, with or without radiotherapy. Continuation to 6 months or until progression, unacceptable toxicity or withdrawal.

ALK rearrangement. Lorlatinib, 100 mg once daily, oral tablets, plus pembrolizumab, 200 mg every 3 weeks, intravenous infusion, with or without radiotherapy. Continuation to 6 months or until progression, unacceptable toxicity or withdrawal.

Disease deemed unsuitable for active treatment. Best supportive care with palliative care involvement, continued for the duration of the participant’s involvement in the study to 6 months, with follow-up to 12 months. Outcomes are captured for comparison.

Monitoring and adherence. Where treatment is commenced, adherence to oral agents is monitored through monthly clinical review, pharmacy dispensing records and participant report; intravenous immunotherapy administration is recorded in the hospital medical record. All participants undergo monthly clinical assessment and blood tests, 3-monthly CT of neck, chest, abdomen and pelvis, 3-monthly circulating tumour DNA sampling, and 18F-FDG PET/CT at 3 and 6 months. Whole-body PD-L1 PET/CT at 3 and 6 months is an exploratory assessment conducted within the IMPRINT imaging sub-study, which is to be registered separately.
Intervention code [1] 335383 0
Diagnosis / Prognosis
Intervention code [2] 335384 0
Treatment: Drugs
Intervention code [3] 335385 0
Treatment: Other
Description of the comparator or control
Historical controls. Two sources are used.

First, an institutional cohort of 59 patients with anaplastic thyroid cancer managed at Royal North Shore Hospital, St Leonards, New South Wales, a tertiary referral centre, between 1979 and 2018. Data were drawn from the Royal North Shore Hospital endocrine surgery database, maintained prospectively for more than 25 years, and have been published (Jonker et al., Ann Surg Oncol 2021;28(12):7520-7530). The cohort comprised stage IVA disease in 2 patients, stage IVB in 28 and stage IVC in 29, with a median age of 73 years. Excluding patients who had received molecular targeted therapy, progression-free survival in this cohort was 40%.

Second, published international cohorts of patients with anaplastic thyroid cancer, comprising: a retrospective cohort of 479 patients treated at the MD Anderson Cancer Center, Houston, United States, between 2000 and 2019 (Maniakas et al., JAMA Oncol 2020;6(9):1397-1404); and a multicentre cohort from the ENDOCAN-TUTHYREF network, France (Jannin et al., Thyroid 2023;33(10):1190-1200), covering the period reported in that publication.

Because anaplastic thyroid cancer is rare and requires urgent treatment initiation, a randomised controlled trial is not feasible in this setting, and historical and international data therefore serve as the comparator. Analyses will account for disease stage, acknowledging that the majority of participants are expected to have higher-stage disease.
Control group
Historical

Outcomes
Primary outcome [1] 346939 0
Progression-free survival
Timepoint [1] 346939 0
6 months after participant entry into the RADAR pathway
Secondary outcome [1] 468185 0
Overall survival
Timepoint [1] 468185 0
Ongoing from participant entry into the RADAR pathway until 6 months, with follow-up continuing to 12 months
Secondary outcome [2] 468186 0
Time from referral to multidisciplinary team assessment
Timepoint [2] 468186 0
Per participant at time of multidisciplinary team meeting; reported in aggregate at 6 months post-RADAR commencement
Secondary outcome [3] 468187 0
Time from referral to core needle biopsy
Timepoint [3] 468187 0
Per participant at time of biopsy; reported in aggregate at 6 months post-RADAR commencement
Secondary outcome [4] 469865 0
Time from biopsy to availability of immunohistochemistry result
Timepoint [4] 469865 0
Per participant at time of result; reported in aggregate at 6 months post-RADAR commencement
Secondary outcome [5] 469866 0
Time from biopsy to availability of next-generation sequencing result
Timepoint [5] 469866 0
Per participant at time of result; reported in aggregate at 6 months post-RADAR commencement
Secondary outcome [6] 469867 0
Time from referral to commencement of definitive treatment
Timepoint [6] 469867 0
Per participant at treatment commencement; reported in aggregate at 6 months post-RADAR commencement
Secondary outcome [7] 469868 0
Adverse events
Timepoint [7] 469868 0
Monthly from treatment commencement to 6 months post-RADAR commencement
Secondary outcome [8] 469869 0
Immune-related adverse events
Timepoint [8] 469869 0
Monthly from treatment commencement to 6 months post-RADAR commencement
Secondary outcome [9] 469870 0
Metabolic response of tumour
Timepoint [9] 469870 0
Baseline, 3 months and 6 months post-RADAR commencement
Secondary outcome [10] 469871 0
Quality of life
Timepoint [10] 469871 0
Baseline, post-treatment, 3 months and 6 months post-RADAR commencement
Secondary outcome [11] 469872 0
Cost-effectiveness of treatment
Timepoint [11] 469872 0
6 months post-RADAR commencement

Eligibility
Key inclusion criteria
Aged 18 years or older.
Histopathologically confirmed diagnosis of anaplastic thyroid cancer, preferably established by core needle biopsy.
Referred to Department of Diabetes, Endocrinology and Metabolism, Royal North Shore Hospital.
Able to provide informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Healthy volunteers
No
Key exclusion criteria
Unable to provide informed consent.
Diagnosis of advanced differentiated thyroid cancer, or poorly differentiated thyroid cancer, that does not meet diagnostic criteria for anaplastic thyroid cancer.
Pregnancy, or within six weeks post-partum, owing to the teratogenicity of targeted agents and immunotherapy.
Aged under 18 years.

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
Other
Other design features
Single-arm intervention compared with historical control groups. All participants receive the same intervention, the RADAR rapid multidisciplinary assessment pathway. There is no randomisation and no concurrent control group. Outcomes are compared with historical control cohorts, comprising an institutional cohort of 59 patients with anaplastic thyroid cancer managed at Royal North Shore Hospital between 1979 and 2018, and published international cohorts. Following molecular profiling, the multidisciplinary team issues a treatment recommendation based on mutation status together with assessment of resectability and fitness for active treatment; these recommendations are not trial-allocated arms and the drug treatments are not supplied or funded by the trial.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
30/06/2026
Date of last participant enrolment
Anticipated
30/11/2028
Actual
Date of last data collection
Anticipated
28/02/2030
Actual
Sample size
Target
12
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 30238 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 46637 0
2065 - St Leonards

Funding & Sponsors
Funding source category [1] 323057 0
Hospital
Name [1] 323057 0
Royal North Shore Hospital, Northern Sydney Local Health District
Country [1] 323057 0
Australia
Funding source category [2] 323059 0
Government body
Name [2] 323059 0
Cancer Institute NSW
Country [2] 323059 0
Australia
Funding source category [3] 323060 0
Government body
Name [3] 323060 0
NSW Health Pathology (Pathology North)
Country [3] 323060 0
Australia
Primary sponsor type
Government body
Name
Northern Sydney Local Health District
Address
Country
Australia
Secondary sponsor category [1] 326002 0
None
Name [1] 326002 0
Address [1] 326002 0
Country [1] 326002 0
Other collaborator category [1] 284104 0
University
Name [1] 284104 0
University of Sydney
Address [1] 284104 0
Country [1] 284104 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 321459 0
Northern Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 321459 0
Ethics committee country [1] 321459 0
Australia
Date submitted for ethics approval [1] 321459 0
28/10/2025
Approval date [1] 321459 0
22/01/2026
Ethics approval number [1] 321459 0
2025/ETH02450

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

Contacts
Principal investigator
Name 153794 0
A/Prof Matti L Gild
Address 153794 0
Department of Endocrinology, Level 3 Acute Services Building, Royal North Shore Hospital, Reserve Road, St Leonards, NSW, 2065
Country 153794 0
Australia
Phone 153794 0
+61 2 9463 1466
Fax 153794 0
Email 153794 0
[email protected]
Contact person for public queries
Name 153795 0
Dr Stephen Ludgate
Address 153795 0
Department of Endocrinology, Level 3 Acute Services Building, Royal North Shore Hospital, Reserve Road, St Leonards, NSW, 2065
Country 153795 0
Australia
Phone 153795 0
+61 2 9463 1466
Fax 153795 0
Email 153795 0
[email protected]
Contact person for scientific queries
Name 153796 0
Matti L Gild
Address 153796 0
Department of Endocrinology, Level 3 Acute Services Building, Royal North Shore Hospital, Reserve Road, St Leonards, NSW, 2065
Country 153796 0
Australia
Phone 153796 0
+61 2 9463 1466
Fax 153796 0
Email 153796 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No
No IPD sharing reason/comment: Individual participant data will not be shared. Participant consent obtained under this protocol does not extend to sharing of individual participant data outside the study team. Given the rarity of anaplastic thyroid cancer and the small single-site sample, individual participant data cannot be adequately de-identified without risk of re-identification. De-identified population-level results will be published.



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
No additional documents have been identified.