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Multicenter Study Differentiated Thyroid Carcinoma

This study has been completed.
Sponsor:
Collaborator:
Deutsche Krebshilfe e.V., Bonn (Germany)
Information provided by:
University Hospital Muenster
ClinicalTrials.gov Identifier:
NCT00144079
First received: September 1, 2005
Last updated: May 8, 2006
Last verified: September 2005
  Purpose

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.


Condition Intervention Phase
Thyroid Neoplasms
Procedure: external beam radiotherapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 3 Trial of Adjuvant External Beam Radiotherapy for Locally Invasive Differentiated Thyroid Carcinoma

Resource links provided by NLM:


Further study details as provided by University Hospital Muenster:

Primary Outcome Measures:
  • time to local or distant failure
  • cancer-related mortality

Secondary Outcome Measures:
  • acute toxicity of radiotherapy (RTOG)
  • chronic toxicity of radiotherapy (RTOG)
  • quality of life

Estimated Enrollment: 500
Study Start Date: January 2000
Estimated Study Completion Date: January 2010
Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00144079

Locations
Austria
Department of Nuclear Medicine
Linz, Austria, 4010
Department of Nuclear Medicine, Wien University Hospital
Wien, Austria, 1090
Germany
Department of Nuclear Medicine, University Halle-Wittenberg
Halle, Germany, 06097
Department of Nuclear medicine, Saarland University
Homburg/Saar, Germany, 66421
Department of Nuclear Medicine, Cologne University
Köln, Germany, 50924
Department of Nuclear Medicine, Münster University Hospital
Münster, Germany, 48129
Department of Nuclear Medicine, Katharinen-Hospital
Stuttgart, Germany, 70174
Department of Nuclear Medicine, Helios-Klinikum Wuppertal
Wuppertal, Germany, 44283
Department of Nuclear Medicine, Würzburg University
Würzburg, Germany, 97080
Switzerland
Department of Nuclear Medicine, Zürich University Hospital
Zürich, Switzerland, 8091
Sponsors and Collaborators
University Hospital Muenster
Deutsche Krebshilfe e.V., Bonn (Germany)
Investigators
Study Chair: Otmar Schober, Prof MD PhD Department of Nuclear Medicine, Münster University Hospital, Münster, Germany
Study Director: Henning Dralle, Prof MD Dept. of General Surgery, University Halle-Wittenberg, Halle, Germany
Study Director: Normann Willich, Prof MD Department of Radiooncology, Münster University Hospital, Münster, Germany
Study Director: Martin Biermann, MD Dept. of Nuclear Medicine, Münster University Hospital
Study Director: Burkhard Riemann, MD PhD Dept. of Nuclear Medicine, Münster University Hospital
Study Director: Andreas Schuck, MD PhD Dept. of Radiooncology, Münster University Hospital
  More Information

Additional Information:
Publications:
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, 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.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00144079     History of Changes
Other Study ID Numbers: MSDS, Deutsche Krebshilfe 70-2294
Study First Received: September 1, 2005
Last Updated: May 8, 2006
Health Authority: Germany: Ethics Commission

Keywords provided by University Hospital Muenster:
Differentiated thyroid carcinoma
radiotherapy
radioiodine therapy
thyroidectomy

Additional relevant MeSH terms:
Carcinoma
Thyroid Diseases
Thyroid Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Head and Neck Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on November 25, 2014