Multicentric phase III trial comparing two strategies in intermediate-risk differentiated thyroid cancer patients: Systematic radioiodine administration versus decision of radioiodine treatment guided by a post-operative work-up based on serum Tg values and diagnostic RAI scintigraphy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Francois Baclesse

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

2 Mar 2020 → ongoing

Decision date (initial)

2024-06-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

INCa (PHRC-K)

External identifiers

EU CT number

2024-514603-34-00

EudraCT number

2019-002968-27

ClinicalTrials.gov

NCT04290663

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

- To assess whether a strategy of RAI-treatment guided by a post-operative work-up is non-inferior to a systematic RAI-treatment strategy in terms of excellent response rate at 3 years post-randomization in a “low-risk” subgroup of patients within the intermediate-risk category

Secondary objectives 6

1. - To compare both strategies in terms of: • Rate of excellent response at 1 and 5 years • Patient’s quality-of-life (SF-36 questionnaire), anxiety (STAI), impact of event scale (IES) and fear of cancer recurrence, at inclusion, end of diagnostic assessment, end of treatment (for treated patients), 1 year and 3 years • Salivary, nasal and lachrymal toxicities at inclusion, end of diagnostic assessment, end of treatment (for treated patients), 1 year and 3 years • Supplemental treatments (RAI, surgery, others) performed within the 5 years of follow-up • Management cost over 5 years.
2. - To compare diagnostic and post-therapeutic scintigraphy (in the guided follow-up group)
3. - To assess the added value of diagnostic RAI scintigraphy in decision-making for RAI treatment (in the guided follow-up group)
4. - To assess the predictive value of post-operative serum Tg level under Thyroxine (Tg/LT4) and after rhTSH (Tg/rhTSH) on the presence of RAI-avid lesions on the post-therapeutic scintigraphy in the RAI group, and on the excellent response rate at 3 years in both groups
5. - To assess the excellent response rate at 3 and 5 years after randomization in case of supplemental treatments
6. - To collect a tumor biobank for further translational research with somatic molecular markers such as BRAF and TERTp mutations

Conditions and MedDRA coding

intermediate-risk differentiated thyroid cancer patients

Study design 2 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. • Subgroup of patients with differentiated thyroid cancer and intermediate-risk defined as follows according to TNM 2017: o Papillary thyroid cancer (PTC) without aggressive subtype, follicular thyroid cancer (FTC) (with < 4 foci of vascular invasion) or Hürthle cell carcinoma (HCC) o T1b or T2 with minimal extra-thyroid extension into the perithyroidal soft tissues and/or pN1 with largest nodal dimension between 2 and 10 mm, without extra-capsular invasion and with a number of metastatic nodes ≤ 10 o T1aN1 with largest nodal dimension between 2 and 10 mm, without extra-capsular invasion and with a number of metastatic nodes ≤ 10
2. • Patient treated by total thyroidectomy with macroscopically complete tumor resection (R0 or R1) ± neck dissection
3. • Total thyroidectomy performed within 6 to 14 weeks before randomization
4. • Patient with or without anti-thyroglobulin antibodies (TgAb)
5. • No known distant metastases
6. • Normal post-operative neck ultrasound (US) or if doubtful US, negative cytology and normal Tg value (<10 ng/ml) in FNA washout fluid
7. • Post-operative LT4 treatment initiated at least 6 weeks before randomization
8. • Performance Status 0 or 1
9. • Patients aged 18 years or older
10. • Signed informed consent form
11. • Patient who agrees to be followed annually during 5 years
12. • Patient affiliated to the French social security system

Exclusion criteria 10

1. • Patients with: o medullary or anaplastic thyroid cancer o or poorly differentiated carcinoma o or well differentiated FTC with at least 4 foci of vascular invasion o or PTC with aggressive variants (tall cell or columnar cell carcinoma, diffuse sclerosing papillary, hobnail variant) o NIFTP (Noninvasive follicular thyroid neoplasm with papillary-like nuclear features)
2. • Low-risk or high-risk DTC patients according to ATA 2015, and intermediate-risk patients with extra-thyroid extension into the perithyroidal muscles (pT3b according to pTNM 2017), and/or pN1 with nodal largest dimension >10 mm or with extra-capsular invasion or more than 10 metastatic nodes. This excludes the following patients: o All pT3 or pT4 o pT1aN0/x with or without minimal extra-thyroid extension o pT1bN0/x, pT2N0/Nx without minimal extra-thyroid extension o pT1aN1 or pT1bN1 or pT2N1 without extra-thyroid extension and with nodal largest dimension <2mm o pT1aN1 or pT1bN1 or pT2N1 without extra-thyroid extension and with nodal largest dimension >10mm o Surgery considered as macroscopically incomplete (R2)
3. • Patients who have undergone lobectomy only
4. • Post-operative neck US with metastatic lymph-nodes confirmed by cytology or by increased Tg (>10 ng/ml) in FNA washout fluid
5. • Drugs affecting thyroid function including iodinated contrast agents in the 6 weeks prior to randomization. Amiodarone should have been stopped at least 1 year before randomization.
6. • Previous RAI treatment for thyroid cancer
7. • Pregnant or lactating women
8. • Any associated geographical, social or psychopathological condition that could compromise the patient's ability to participate in the study
9. • Patient deprived of liberty or placed under the authority of a tutor
10. • History of malignancy in the past 3 years, except skin cancer excluding melanoma, carcinoma in situ of the cervix. Any other solid tumor or lymphoma (without bone marrow involvement) must have been treated and not have shown signs of recurrence for at least 3 years

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. - The primary endpoint is the rate of patients with excellent response (normal neck ultrasonography and Tg/LT4 <0.2 ng/mL and absence of TgAb and if performed, no abnormalities on other imaging modalities), at 3 years post-randomization

Secondary endpoints 9

1. - Excellent response rate at 1 and 5 years post-randomization, defined as above, will be used for non-inferiority comparison
2. - The scores on HRQoL, anxiety and fear of cancer recurrence will be calculated according to the corresponding scoring manual from the various questionnaires at inclusion, end of diagnostic assessment, end of treatment (for treated patients), 1 year and 3 years. The lachrymal, nasal and salivary glands toxicities will be evaluated from specific questionnaires at inclusion, end of diagnostic assessment, end of treatment (for treated patients), 1 year and 3 years
3. - Supplemental treatments (surgery, RAI administration or others) performed within 5 years post-randomization in both groups. The response to these treatments will be defined according to the 2015 ATA guidelines: excellent response, biochemical incomplete response, structural incomplete response, and indeterminate response
4. - Costs within 5 years post-randomization in both groups, from the French collective perspective, taking into account the resources such as:  External consultations, hospitalizations  Imaging exams (neck-US, scintigraphy, CT scans…)  Biological exams  Transportation related to the care  Study treatments: I131 and rhTSH  Treatment for possible recurrence (surgery, RAI administration or others)  Sick leave related to thyroid cancer
5. - The results of diagnostic and post-therapeutic scintigraphy (in the guided follow-up group)
6. - The proportion of patients for whom the results of the diagnostic RAI scintigraphy have changed the decision-making for RAI treatment (in the guided follow-up group)
7. - The post-operative serum Tg levels on Levothyroxine treatment (Tg/LT4) and after rhTSH (Tg/rhTSH) to assess their predictive value on the presence of RAI-avid lesions in the RAI group and on the rate of excellent response at 3 years in both groups
8. - The excellent response rate at 3 and 5 years after randomization in case of supplemental treatments
9. - The predictive values of somatic molecular markers (especially BRAF and TERTp) on the risk of persistent disease

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Francois Baclesse

Sponsor organisation

Centre Francois Baclesse

Address

3 Avenue Du General Harris, Cs 45026 Cs 45026

City

Caen Cedex 5

Postcode

14076

Country

France

Scientific contact point

Organisation

Centre Francois Baclesse

Contact name

Stéphane BARDET

Public contact point

Organisation

Centre Francois Baclesse

Contact name

Stéphane BARDET

Locations

1 EU/EEA country · 29 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications