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Differentiated Thyroid Cancer: is There a Need for Radioiodine Ablation in Low Risk Patients? (ESTIMABL2)

Primary Purpose

Low Risk Differentiated Thyroid Cancer

Status

Active

Phase

Phase 3

Locations

France

Study Type

Interventional

Intervention

rhTSH stimulation

I131

Follow up

About this trial

This is an interventional other trial for Low Risk Differentiated Thyroid Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients with differentiated thyroid cancer (papillary, follicular or with Hurthle cells) in the absence of aggressive histological subtypes (poorly differentiated, tall-clear-cylindric cell, diffuse sclerosing or with an anaplastic component)
Patients having undergone a total thyroidectomy with complete (R0) tumor resection, with or without lymph node neck dissection
Total thyroidectomy performed 2 to 5 months before inclusion
Patients with low risk of recurrence: pT1amN0 or pT1amNx with a sum of the size of the lesions above 1 cm and equal to or less than 2 cm, or pT1bN0 or pT1bNx (TNM 2010 classification).
Post-operative neck ultrasound (performed 2 to 5 months after surgery) showing the absence of abnormalities in the lateral lymph node compartments, or if abnormalities, no lymph nodes with abnormal cytology and/or thyroglobulin concentration in the aspirate fluid > 10 ng/mL
Age >=18 years
Performance status of 0 or 1
Patients who signed the informed consent
Patients who can be followed-up annually during 5 years in order to assess the objectives of the study
Women of childbearing age should have a negative pregnancy test before any radioiodine administration
Both patients with or without thyroglobulin antibodies are eligible

Exclusion Criteria:

Patients having undergone less than a total thyroidectomy
Patients with aggressive histotype (poorly differentiated, tall-clear-cylindric cell, diffuse sclerosing, or with an anaplastic component)
Patients having undergone total thyroidectomy less than 2 months or more than 5 months before inclusion
Patients with cancer classified as pT1a unifocal (in which ablation is not necessary), or pT1N1, pT2, pT3, pT4 or N1 (who have a higher risk of recurrence) (classification TNM 2010)
Patient with known distant metastasis
Abnormal post-operative neck ultrasound of the lateral lymph node compartments
Patients with another malignancy not in remission for at least 2 years (except for in situ cervix uterine cancer, basocellular skin cancer)
Patients with a recent history of drugs affecting thyroid function, including injection of radiocontrast agents during the last 8 weeks.
Patients previously treated with radioactive iodine or who previously underwent a whole body scan with radioactive iodine
Pregnant or breast feeding women
Subject with any kind of disorder that may compromise his/her ability to give written informed consent and/or to comply with study procedures

Sites / Locations

Institut Gustave Roussy

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Ablation group

Follow up group

Arm Description

Administration of 1.1 GBq of I131 is given after the second intramuscular injections of rhTSH (0.9 mg). A whole body scan (WBS) is performed 2 to 5 days after the administration or I131 with determination of the neck uptake. Follow-up consists in: 10 (+/- 2 months) after randomization: neck ultrasound + a serum Tg measurement after rhTSH stimulation 2 years (+/- 2 months) after randomization: serum Tg measurement under LT4 treatment (Tg/LT4) 3 years (+/- 2 months) after randomization: neck ultrasound and a serum Tg/LT4 4 years (+/- 2 months) after randomization: a serum Tg/LT4 5 years (+/- 2 months) after randomization: a neck ultrasound and a serum Tg/LT4 8 years (+/- 2 months) after randomization: a neck ultrasound and a serum Tg/LT4 10 years (+/- 2 months) after randomization: a neck ultrasound and a serum Tg/LT4 12 years (+/- 2 months) after randomization: a neck ultrasound and a serum Tg/LT4

Patients randomized in the follow up group neither received 131I nor rhTSH. Patients will undergo the same followup procedures as patients randomized to the ablation group, except that at 10 months after randomization, Tg will be measured under LT4 treatment and not after rhTSH stimulation.

Outcomes

Primary Outcome Measures

Rate of patient without event at 3 years following randomization

Secondary Outcome Measures

Lachrymal and Salivary Glands Toxicities

Patient's quality of life, anxiety and fear of recurrence

Rate of patients without event

Rate of events adjusted on the initial lymph node status

Recurrence rate (histologically proven)

Rate of cure after an event

Cost of treatment and follow-up

Rate of events adjusted on tumoral molecular characterization

Full Information

NCT ID

NCT01837745

First Posted

April 16, 2013

Last Updated

May 16, 2023

Sponsor

Gustave Roussy, Cancer Campus, Grand Paris

1. Study Identification

Unique Protocol Identification Number

NCT01837745

Brief Title

Differentiated Thyroid Cancer: is There a Need for Radioiodine Ablation in Low Risk Patients?

Acronym

ESTIMABL2

Official Title

Differentiated Thyroid Cancer: is There a Need for Radioiodine Ablation in Low Risk Patients?

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

May 13, 2013 (Actual)

Primary Completion Date

April 1, 2022 (Actual)

Study Completion Date

January 1, 2030 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Gustave Roussy, Cancer Campus, Grand Paris

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Open-label randomized phase III trial, using a non-inferiority comparison design. After randomization,patients will receive either post-operative radioiodine ablation with an activity of 1.1 GBq (30 mCi) after stimulation by rhTSH, and then be followed-up (ablation group) or be followed-up (without postoperative radioiodine ablation) (follow-up group). The objective is to assess the non-inferiority of the proportion of patients without tumor-related event evaluated at three years after randomisation in the absence of radioiodine ablation (follow-up group) compared to the ablation group, in patients with low-risk differentiated thyroid cancer treated with total thyroidectomy with or without lymph node dissection (pT1am N0 or Nx, pT1b N0 or Nx)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Low Risk Differentiated Thyroid Cancer

7. Study Design

Primary Purpose

Other

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

776 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ablation group

Arm Type

Active Comparator

Arm Description

Arm Title

Follow up group

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

rhTSH stimulation

Other Intervention Name(s)

Thyrogen

Intervention Description

Intramuscular injections of rhTSH (0.9 mg) on two consecutive days on LT4 treatment

Intervention Type

Drug

Intervention Name(s)

I131

Intervention Description

An activity of 1.1 GBq of I131 is given orally 24 hours after the second injection of rhTSH.

Intervention Type

Other

Intervention Name(s)

Follow up

Intervention Description

10 (+/- 2 months) after randomization: a neck ultrasound and a serum Tg measurement after rhTSH or LT4 stimulation 2 years (+/- 2 months) after randomization: a serum Tg measurement under LT4 treatment (Tg/LT4) 3 years (+/- 2 months) after randomization: a neck ultrasound and a serum Tg/LT4 4 years (+/- 2 months) after randomization: a serum Tg/LT4 5 years (+/- 2 months) after randomization: a neck ultrasound and a serum Tg/LT4 8 years (+/- 2 months) after randomization: a neck ultrasound and a serum Tg/LT4 10 years (+/- 2 months) after randomization: a neck ultrasound and a serum Tg/LT4 12 years (+/- 2 months) after randomization: a neck ultrasound and a serum Tg/LT4

Primary Outcome Measure Information:

Title

Rate of patient without event at 3 years following randomization

Time Frame

assessed up to 3 years

Secondary Outcome Measure Information:

Title

Lachrymal and Salivary Glands Toxicities

Time Frame

Assessed up at baseline, 2 months, 10 months and 3 years after randomization

Title

Patient's quality of life, anxiety and fear of recurrence

Time Frame

at inclusion, 2 months after inclusion, 10 months and 3 years after randomization

Title

Rate of patients without event

Time Frame

at 5 years following randomization

Title

Rate of events adjusted on the initial lymph node status

Time Frame

at 3 and 5 years following randomization

Title

Recurrence rate (histologically proven)

Time Frame

at 3 years following randomization and then at 5 years

Title

Rate of cure after an event

Time Frame

at 5 years after randomization

Title

Cost of treatment and follow-up

Time Frame

at 3 years after randomization

Title

Rate of events adjusted on tumoral molecular characterization

Time Frame

3 and 5 years after randomization

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients with differentiated thyroid cancer (papillary, follicular or with Hurthle cells) in the absence of aggressive histological subtypes (poorly differentiated, tall-clear-cylindric cell, diffuse sclerosing or with an anaplastic component) Patients having undergone a total thyroidectomy with complete (R0) tumor resection, with or without lymph node neck dissection Total thyroidectomy performed 2 to 5 months before inclusion Patients with low risk of recurrence: pT1amN0 or pT1amNx with a sum of the size of the lesions above 1 cm and equal to or less than 2 cm, or pT1bN0 or pT1bNx (TNM 2010 classification). Post-operative neck ultrasound (performed 2 to 5 months after surgery) showing the absence of abnormalities in the lateral lymph node compartments, or if abnormalities, no lymph nodes with abnormal cytology and/or thyroglobulin concentration in the aspirate fluid > 10 ng/mL Age >=18 years Performance status of 0 or 1 Patients who signed the informed consent Patients who can be followed-up annually during 5 years in order to assess the objectives of the study Women of childbearing age should have a negative pregnancy test before any radioiodine administration Both patients with or without thyroglobulin antibodies are eligible Exclusion Criteria: Patients having undergone less than a total thyroidectomy Patients with aggressive histotype (poorly differentiated, tall-clear-cylindric cell, diffuse sclerosing, or with an anaplastic component) Patients having undergone total thyroidectomy less than 2 months or more than 5 months before inclusion Patients with cancer classified as pT1a unifocal (in which ablation is not necessary), or pT1N1, pT2, pT3, pT4 or N1 (who have a higher risk of recurrence) (classification TNM 2010) Patient with known distant metastasis Abnormal post-operative neck ultrasound of the lateral lymph node compartments Patients with another malignancy not in remission for at least 2 years (except for in situ cervix uterine cancer, basocellular skin cancer) Patients with a recent history of drugs affecting thyroid function, including injection of radiocontrast agents during the last 8 weeks. Patients previously treated with radioactive iodine or who previously underwent a whole body scan with radioactive iodine Pregnant or breast feeding women Subject with any kind of disorder that may compromise his/her ability to give written informed consent and/or to comply with study procedures

Facility Information:

Facility Name

Institut Gustave Roussy

City

Villejuif

State/Province

Val De Marne

ZIP/Postal Code

94805

Country

France

12. IPD Sharing Statement

Citations:

PubMed Identifier

35263518

Citation

Leboulleux S, Bournaud C, Chougnet CN, Zerdoud S, Al Ghuzlan A, Catargi B, Do Cao C, Kelly A, Barge ML, Lacroix L, Dygai I, Vera P, Rusu D, Schneegans O, Benisvy D, Klein M, Roux J, Eberle MC, Bastie D, Nascimento C, Giraudet AL, Le Moullec N, Bardet S, Drui D, Roudaut N, Godbert Y, Morel O, Drutel A, Lamartina L, Schvartz C, Velayoudom FL, Schlumberger MJ, Leenhardt L, Borget I. Thyroidectomy without Radioiodine in Patients with Low-Risk Thyroid Cancer. N Engl J Med. 2022 Mar 10;386(10):923-932. doi: 10.1056/NEJMoa2111953.

Results Reference

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Differentiated Thyroid Cancer: is There a Need for Radioiodine Ablation in Low Risk Patients?

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