Multicenter Study Differentiated Thyroid Carcinoma

Thyroid Neoplasms Clinical Trial

Official title:

Phase 3 Trial of Adjuvant External Beam Radiotherapy for Locally Invasive Differentiated Thyroid Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00144079
• Other study ID #: MSDS
• Secondary ID: Deutsche Krebshi
• Status: Completed
• Phase: Phase 3
• First received: September 1, 2005
• Last updated: May 8, 2006
• Start date: January 2000
• Est. completion date: January 2010

Study information

• Verified date: September 2005
• Source: University Hospital Muenster
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ethics Commission
• Study type: Interventional

Clinical Trial Summary

The trial examines the clinical benefit of adjuvant external beam radiotherapy (RTx) for locally invasive differentiated carcinoma (TNM stages pT4 pN0/1/x M0/x; 5th ed. 1997) of the thyroid gland (DTC). Patients are treated with surgery (thyroidectomy and lymphadenectomy), radioiodine therapy (RIT) to ablate the thyroid remnant tissue, and TSH-suppressive L-thyroxine therapy with or without RTx after documented elimination of cervical I-131 uptake.

Description:

MSDS was designed as a comprehensive cohort trial with randomization and observation arms. Patients are enrolled at the time of the first ablative radioiodine therapy (RIT). Inclusion criteria are papillary or follicular DTC pT4 pN0/1/x M0/x, age between 18 (incl.) and 70 years (excl.) at the time of initial surgery, completion of primary surgical therapy with R0 (no tumor residues) or R1 (microscopic residues) resection, Karnofsky index of at least 70 %, freedom from distant metastases at the time of initial radioiodine therapy (RIT), and informed patient consent. Criteria for exclusion are secondary malignancy except basalioma, pregnancy, serious general disease, serious psychiatric disorder, inability to give informed consent, previous RTx and recurrence of previous DTC. From 2003, the first inclusion criterion was changed into DTC pT3/4 pN0/1/x M0/x to reflect the 2002 revision of the TNM staging system.

The treatment protocol is in accordance with current guidelines in Germany and includes total thyroidectomy (TT) with central lymphadenectomy (LNA), RIT to ablate the thyroid remnant, and TSH-suppressive therapy with L-thyroxine (TSH < 0.1 mU/l). RIT is administered under endogenous TSH-stimulation after 4 weeks’ cessation of L-thyroxine using standard activities of 1–4, and 1–2, GBq I-131 in patients with a 24-h-I-131 uptake below 10 % and 10–20 %, resp., or individual dosimetry aiming for at least 300 Gy in the thyroid remnant. If scintigraphic I-131 uptake by the thyroid remnant persists at whole-body scintigraphy (at least 200 MBq; at least 48 h) 3 months after RIT, a second fraction of RIT is given with 4–10 GBq.

Patients who consented to randomization at centers actively taking part in randomization were randomized to treatment arms A (additional adjuvant RTx) and B (no RTx) 3 months after initial RIT after confirmation of the histological diagnosis by the reference pathologist and when distant metastases had been excluded by means of serum thyroglobulin (Tg), WBS (s. a.) and a native thoracic computed tomogram (CCT). Randomization was stratified according to histological type (papillary v. follicular), nodal status (pN0/1/x), and participating center, and performed by an operator-independent randomization routine embedded in the database. The remaining patients were assigned to arms A and B by the participating centers.

RTx is begun after documented elimination of cervical I-131 uptake in a I-131 WBS 3 months after the last fraction of ablative RIT. RT includes the thyroid bed (in unilateral tumors only the affected side) with a dose of 59.4 Gy and 66.6 Gy after R0 and R1 resection, resp., and the regional lymph nodes of the neck and upper mediastinum including the posterior cervical chain from the mandible and mastoid process to the tracheal bifurcation with a dose of 50.4 Gy and 54.0 Gy in pN0 and pN1/x disease, resp. Fractionation is conventional (1.8 Gy/d 5 days a week). 3-D planning according to IRCU 50 is mandatory.

Patient follow-up includes, as a minimum, out-patient appointments with cervical ultrasound and measurement of serum TSH, hTG, anti-Tg antibodies and a blood count 2 and 8 months after each RIT or WBS, and a WBS (with at least 200 MBq over at least 48 h) under endogenous TSH-stimulation 3 and 12 months after ablative RIT and then at 24-month intervals. FDG-PET and other imaging modalities can be performed if needed. At each follow-up appointment, RTx toxicity is recorded according to RTOG criteria and quality of life by the QLQ-C30 questionnaire (v. 3.0 German) of the EORTC.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 500
• Est. completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 69 Years

Eligibility

Inclusion Criteria:

• papillary or follicular thyroid carcinoma pT4 pN0/1/x M0/x

• completion of primary surgical therapy with R0 (no tumor residues) or R1 (microscopic residues) resection

• Karnofsky index > 70 %

• freedom from distant metastases at the time of initial radioiodine therapy

• informed patient consent

Exclusion Criteria:

• secondary malignancy except basalioma

• pregnancy

• serious general disease

• serious psychiatric disorder

• inability to give informed consent

• previous RTx

• recurrence of previous thyroid cancer

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Thyroid Diseases
• Thyroid Neoplasms

Intervention

Procedure:
• external beam radiotherapy

Locations

Country	Name	City	State
Austria	Department of Nuclear Medicine	Linz
Austria	Department of Nuclear Medicine, Wien University Hospital	Wien
Germany	Department of Nuclear Medicine, University Halle-Wittenberg	Halle
Germany	Department of Nuclear medicine, Saarland University	Homburg/Saar
Germany	Department of Nuclear Medicine, Cologne University	Köln
Germany	Department of Nuclear Medicine, Münster University Hospital	Münster
Germany	Department of Nuclear Medicine, Katharinen-Hospital	Stuttgart
Germany	Department of Nuclear Medicine, Helios-Klinikum Wuppertal	Wuppertal
Germany	Department of Nuclear Medicine, Würzburg University	Würzburg
Switzerland	Department of Nuclear Medicine, Zürich University Hospital	Zürich

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital Muenster	Deutsche Krebshilfe e.V., Bonn (Germany)

Countries where clinical trial is conducted

Austria,  Germany,  Switzerland, 

References & Publications (7)

Biermann M, Pixberg M, Schuck A, Willich N, Heinecke A, Schober O. External beam radiotherapy. An evidence-based review. In: Biersack H-J, Grünwald F, eds. Thyroid cancer. Heidelberg: Springer; 139-61, 2005.

Biermann M, Pixberg MK, Dörr U, Dietlein M, Schlemmer H, Grimm J, Zajic T, Nestle U, Ladner S, Sepehr-Rezai S, Rosenbaum S, Puskás C, Fostitsch P, Heinecke A, Schuck A, Willich N, Schmid KW, Dralle H, Schober O; MSDS study group. Guidelines on radioiodine — View Citation

Biermann M, Pixberg MK, Schuck A, Heinecke A, Köpcke W, Schmid KW, Dralle H, Willich N, Schober O. Multicenter study differentiated thyroid carcinoma (MSDS). Diminished acceptance of adjuvant external beam radiotherapy. Nuklearmedizin. 2003 Dec;42(6):244- — View Citation

Biermann M, Schober O. GCP-compliant management of the Multicentric Study Differentiated Thyroid Carcinoma (MSDS) with a relational database under Oracle 8i. Inform Biom Epidemiol Med Biol 33:441-59, 2002

Biermann M, Schober O; Multizentrische Studie Differenziertes Schilddrüsenkarzinom Studiengruppe. [How many high-risk patients with differentiated thyroid cancer need a "Tumor Center" per year?]. Nuklearmedizin. 2002 Apr;41(2):61-2. German. — View Citation

Puskás C, Schober O. [Adjuvant percutaneous radiation of locally advanced papillary and follicular thyroid carcinoma: reflections for the necessity of a prospective multicenter study]. Nuklearmedizin. 1999;38(8):328-32. Review. German. — View Citation

Schuck A, Biermann M, Pixberg MK, Müller SB, Heinecke A, Schober O, Willich N. Acute toxicity of adjuvant radiotherapy in locally advanced differentiated thyroid carcinoma. First results of the multicenter study differentiated thyroid carcinoma (MSDS). St — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	time to local or distant failure
Primary	cancer-related mortality
Secondary	acute toxicity of radiotherapy (RTOG)
Secondary	chronic toxicity of radiotherapy (RTOG)
Secondary	quality of life

External Links

•   Home page of the Department of Nuclear Medicine at Münster University Hospital