Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00005535

Trial Description

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Title

Clinical Evaluation of a I-124 PET/CT Based Remnant Radioiodine Ablation Decision Concept in Differentiated Thyroid Cancer Using PROBE Design

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Trial Acronym

CLERAD-PROBE

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URL of the Trial

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Brief Summary in Lay Language

Thyroid nodules are a common clinical problem. Epidemiologic studies have shown the
prevalence of palpable thyroid nodules to be approximately 5% in women and 1% in men living
in iodine-sufficient parts of the world and up to 30% in iodine deficient regions, such as
Germany. The clinical importance of thyroid nodules rests with the need to exclude thyroid
cancer which occurs in 5-15%. Differentiated thyroid cancer (DTC), which includes papillary
and follicular cancer, comprises the vast majority (90%) of all thyroid cancers. In Germany,
approximately 7,000 new cases will be diagnosed in 2011. The yearly incidence has increased
from 3.6 per 100,000 in 1973 to 8.7 per 100,000 in 2002, and this trend appears to be
continuing. Recurrence-free survival is generally excellent and depends on the risk group.

The role of postoperative remnant radioiodine ablation (RRIA) as the most serious question
regarding the initial management of DTC still needs to be resolved even after decades of
radioiodine use. American Thyroid Association directions for future research addressing
these questions include:

- Better understanding of the long-term risks of radioiodine use;

- Improved risk stratification;

Randomized controlled trials are still missing in which RRIA has proven its worth as a safe
and very effective treatment that results in an improved life expectancy and a reduced
recurrence rate. Many observational studies lack sufficiently high evidence. Evidence grade
is rated mainly on "expert level", based on non-randomized retrospective observation
studies. Although RRIA in Europe is established as adjuvant standard treatment for all
patients with DTC, except those with stage T1a, it remains to be shown throughout if it is
beneficial for low risk and medium risk patients without metastases (M0), also known as
stage I patients according to UICC/AJCC classification, accounting for 40-90% of all
patients.

Blood doses due to cumulative radioiodine therapy may well exceed 2 Gy, and RRIA induces an
average blood dose of 0.28 Gy to the entire body. Risks as estimated from that dose are not
insignificant. The question is whether or not the condition after remnant ablation justifies
such an increased risk of a secondary malignancy. The probability of causation for a
pharyngeal or breast tumour can well exceed the margin of a 50% after being exposed to RRIA
or consecutive I-131 diagnostic imaging to explore measureable Tg levels. Even though
radioiodine therapy can benefit some patients with advanced thyroid carcinoma, it is still
unknown whether the risks of RRIA outweigh any discernable benefit. Undoubtedly, quality of
life may be affected by adjuvant use of I-131.

Study Hypothesis:

The I-124 study arm may have considerable benefits for the patient included in the study.
These include

- enhanced tumour and risk stratification,

- avoidance of unnecessary I-131 exposure in 30-89 percent of patients who were
classified with "low risk" tumour (MACIS or AMES scoring) or "stage I disease"
(UICC-AJCC TNM staging system), and,

- improved quality of life at the same or better morbidity and mortality rates in the
I-124 arm.

Environmental and hospital staff related benefits include prevention or saving of I-131
exposure.

This study is designed to compare effectiveness of treatments following and evaluating
guideline recommendations in two assignment arms.

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Brief Summary in Scientific Language

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Do you plan to share individual participant data with other researchers?

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Description IPD sharing plan:

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Organizational Data

  •   DRKS00005535
  •   2014/05/06
  •   2012/10/04
  •   yes
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Secondary IDs

  •   NCT01704586  (ClinicalTrials.gov)
  •   UKW-NUK-I-124  (University of Wuerzburg)
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Health Condition or Problem studied

  •   Differentiated Thyroid Carcinoma
  •   C73 -  Malignant neoplasm of thyroid gland
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Interventions/Observational Groups

  •   Radiation: Radioiodine I-131
  •   Radiation: I-124
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Blinded
  •   assessor
  •   Active control
  •   Treatment
  •   Parallel
  •   IV
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Primary Outcome

- Mean blood dose after complete remission; time frame: 18 months after thyroid surgery; Both study arms result in different I-131 activity assigned to be administered, depending on remnant ablation and/or metastasis treatment decision. I-131 activity will be standard or less in the standard arm, none in the I-124 arm in patients identified as per protocol not to be administered an ablation activity.

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Secondary Outcome

- Quality of life comparison; time frame: At diagnostic re-evaluations every 4-6 months until 18 months after thyroid surgery; Quality of life will be assessed at each visit a patient is scheduled for re-valuation, using a standardized (SF-36) questionnaire specifically adapted for differentiated thyroid carcinoma.
- Comparison of morbidity and mortality (effectiveness) between the I-124 guided and the standard arm.; time frame: At diagnostic re-evaluations every 4-6 months until 18 months after thyroid surgery; Proportion of patients within the group under I-124 PET/CT guided concept which do not need a RRIA: Because all patients subjected to standard EANM guideline procedures will firstly have RRIA, the proportion of patients can be estimated which is not subjected to unnecessary ablation by applying the I-124 PET/CT guided concept. Thus, we can estimate the proportion of patients in the experimental arm without recurrent tumour or progression (key secondary outcome).
- Prognostic value of thyroglobuline; time frame: At diagnostic re-evaluations every 4-6 months until 18 months after thyroid surgery; The prognostic value of thyroglobuline concentration will be evaluated for both study arms in correlation with tumour stage and imaging modalities.

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

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Recruitment

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  •   2013/01/31
  •   340
  •   Multicenter trial
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   80   Years
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Additional Inclusion Criteria

Inclusion Criteria common for all study subjects prior to randomisation:

- Histologically confirmed new diagnosis of DTC (including Hürthle-cell carcinoma)

- Age 18-80 years

- Performance Status of 0-2

- Tumor stage T1b to T4 with the possibility of lymph node involvement and distant
metastasis according to the [TNM] staging system

- One- or two stage thyroidectomy, with or without central lymph node dissection

- Patient´s written informed consent

- Ability to comply with the protocol procedures

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Exclusion Criteria

Exclusion criteria for all study subjects prior to randomisation:

- Anaplastic or medullary carcinoma

- History of prior malignancy within the past 5 years with limited life-time
expectancy, except for cured non-melanoma skin cancer, cured in situ cervical
carcinoma, or other treated malignancies with no evidence of disease for at least
three years.

- Positive pregnancy test or breast feeding

- Any other severe acute or chronic medical or psychiatric condition, or laboratory
abnormality that would impart, in the judgment of the investigator, excess risk
associated with study participation, or which, in the judgment of the investigator,
would make the patient inappropriate for entry into this study.

- Recent iodine contamination

After Randomisation

I-124 arm:

A: Inclusion criteria for no remnant ablation (low risk DTC):

- Stage I (according to AJCC, ref. 1,33) papillary or follicular carcinoma with the
possibility of lymph node involvement but no distant metastasis and no microscopical
residual disease (Patient age <45y: any T, any N, M0; Patient age 45y or older: T1,
N0, M0)

- I-124 uptake only in thyroid bed

- Absence of aggressive malignant histologic subtypes, including tall-cell, insular,
poorly differentiated and diffuse sclerosing thyroid cancer

B: Inclusion criteria for remnant ablation (high risk DTC):

- All other [TNM] stages (stage II to stage IV C)

- Presence of aggressive malignant histologic subtypes, including tall-cell, insular,
poorly differentiated and diffuse sclerosing thyroid cancer

- I-124 uptake in and outside thyroid bed

Standard arm:

-Standard I-131 ablation concept as defined for all T1b to T4 subjects.

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Addresses

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    • University of Wuerzburg
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    • First Affiliated Hospital, Sun Yat-Sen University
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    • University Clinic Würzburg, Department of Nuclear Medicine
    • Peter Schneider, MD, Prof. 
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    • Peter Schneider, MD, Prof. 
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Sources of Monetary or Material Support

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    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting planned
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Trial Publications, Results and other Documents

  •   American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Pacini F, Schlumberger M, Sherman SI, Steward DL, Tuttle RM. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009 Nov;19(11):1167-214. Erratum in: Thyroid. 2010 Aug;20(8):942. Hauger, Bryan R [corrected to Haugen, Bryan R]. Thyroid. 2010 Jun;20(6):674-5.; 19860577
  •   Luster M, Clarke SE, Dietlein M, Lassmann M, Lind P, Oyen WJ, Tennvall J, Bombardieri E; European Association of Nuclear Medicine (EANM). Guidelines for radioiodine therapy of differentiated thyroid cancer. Eur J Nucl Med Mol Imaging. 2008 Oct;35(10):1941-59.; 18670773
  •   Hay ID. Selective use of radioactive iodine in the postoperative management of patients with papillary and follicular thyroid carcinoma. J Surg Oncol. 2006 Dec 15;94(8):692-700. Review.; 17131429
  •   Hänscheid H, Lassmann M, Luster M, Thomas SR, Pacini F, Ceccarelli C, Ladenson PW, Wahl RL, Schlumberger M, Ricard M, Driedger A, Kloos RT, Sherman SI, Haugen BR, Carriere V, Corone C, Reiners C. Iodine biokinetics and dosimetry in radioiodine therapy of thyroid cancer: procedures and results of a prospective international controlled study of ablation after rhTSH or hormone withdrawal. J Nucl Med. 2006 Apr;47(4):648-54.; 16595499
  •   Tagay S, Herpertz S, Langkafel M, Erim Y, Bockisch A, Senf W, Görges R. Health-related Quality of Life, depression and anxiety in thyroid cancer patients. Qual Life Res. 2006 May;15(4):695-703.; 16688502
  •   Lassmann M, Reiners C, Luster M. Dosimetry and thyroid cancer: the individual dosage of radioiodine. Endocr Relat Cancer. 2010 Jun 3;17(3):R161-72. Print 2010 Sep. Review.; 20448022
  •   Verburg FA, Lassmann M, Mäder U, Luster M, Reiners C, Hänscheid H. The absorbed dose to the blood is a better predictor of ablation success than the administered 131I activity in thyroid cancer patients. Eur J Nucl Med Mol Imaging. 2011 Apr;38(4):673-80. Epub 2011 Jan 6.; 21210115
  •   Passler C, Prager G, Scheuba C, Kaserer K, Zettinig G, Niederle B. Application of staging systems for differentiated thyroid carcinoma in an endemic goiter region with iodine substitution. Ann Surg. 2003 Feb;237(2):227-34.; 12560781
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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   1
  •   2013/12/01
* This entry means the parameter is not applicable or has not been set.