Sorafenib as Adjuvant to Radioiodine Therapy in Non-Medullary Thyroid Carcinoma
Condition: Thyroid Cancer
MeSH terms: Thyroid Neoplasms; Thyroid Cancer, Papillary; Thyroid Diseases
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to assess whether therapy with Sorafenib reinduces radioiodine
      uptake in thyroid carcinoma.
    

Detailed description: 
      Background of the study:

      Therapy with radioiodine (RaI) is the only curative therapy in non-medullary thyroid
      carcinoma. RaI uptake is frequently lost in this disease. Therapy with tyrosine kinase
      inhibitors may restore the susceptibility to RaI.

      Objective of the study:

      To investigate whether therapy with the tyrosine kinase inhibitor Sorafenib will increase the
      accumulation of radioiodine (RaI) and decrease tumor progression in patients with recurrences
      or metastases of non-medullary thyroid carcinoma with absent or insufficient accumulation of
      RaI.

      Study design:

      Prospective, open study with patients with recurrences or metastases of differentiated
      thyroid carcinoma who will undergo 6 months therapy with Sorafenib 800 mg/day. Patients in
      whom RaI uptake will be restored will be offered high dose (6000 MBq) RaI together with an
      additional 6 months treatment with Sorafenib. Patients in whom RaI is not be restored but in
      whom Sorafenib had a favorable effect on tumor growth will be offered continued treatment
      with Sorafenib.

      Study population:

      Thirty patients will be included with recurrences or metastases of differentiated thyroid
      carcinoma that are unresponsive to RaI therapy.

      Intervention (if applicable):

      After inclusion, patients will undergo 131I scintigraphy as well as a CT scan. Thereafter,
      therapy with Sorafenib 800 mg/day will be initiated, and continued during 6 months. After 6
      months, 131I scintigraphy and CT scans will be repeated. Serum levels of thyroglobulin will
      be used as tumormarker.

      Primary study parameters/outcome of the study:

      The endpoint of the study is the proportion of patients with a favorable response to
      Sorafenib defined as ONE OR MORE of the following criteria:

        1. Reinduction of RaI uptake by RaI scintigraphy: The appearance of one or more RaI
           accumulating lesions at RaI scintigraphy, planar images and/or SPECT (see below)

        2. Serum thyroglobulin levels:

           The absence of progression: no statistically significant positive slope at linear
           regression of the log-transformed serum Tg levels, measured at 0, 4, 8, 12, 16, 20, 24
           and 28 weeks after start of Sorafenib:

             -  Stable disease: The slope at linear regression of the log-transformed serum Tg
                levels, measured at 0, 4, 8, 12, 16, 20, 24 and 28 weeks after start of Sorafenib
                is not significantly different from 0 ln ug/L*time OR

             -  Response: The slope at linear regression of the log-transformed serum Tg levels is
                negative (statistically significantly below 0 ln ug/L*time).

        3. CT Imaging:

      The absence of progression according to RECIST criteria:

        -  Stable disease-neither sufficient shrinkage to qualify for partial response nor
           sufficient increase to qualify for progressive disease, taking as reference the smallest
           sum longest diameter since the treatment started.

        -  Partial response-at least a 30% decrease in the sum of the longest diameter of target
           lesions, taking as reference the baseline sum longest diameter;

        -  Complete response: the disappearance of all target lesions
    

Intervention name(s): Sorafenib (nexavar)
Intervention type(s): Drug
Intervention description(s): 6 months therapy with Sorafenib 800 mg/day
Other intervention name(s): nexavar
Intervention MeSH terms: Sorafenib
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment