Patient case: 45-year-old female with medullary thyroid carcinoma; genetic feature: RET

Clinical trial: Sorafenib as Adjuvant to Radioiodine Therapy in Non-Medullary Thyroid Carcinoma

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

Eligibility: Inclusion Criteria:
  -  Patients with non-medullary thyroid carcinoma
  -  The patients must have undergone total thyroidectomy
  -  Presence of metastases or inoperable recurrent disease, as proven by elevated serum thyroglobulin levels (Tg) in combination with radiological evidence for tumor
  -  No or insufficient RaI uptake in tumor as proven by RaI scintigraphy, performed after prior RaI therapy
  Exclusion Criteria:
  -  Pregnancy
  -  Other active malignancies
  -  Active kidney, liver or pancreatic disease or dysfunction
  -  Unstable angina pectoris or recent (<3 months) myocardial infarction.
  -  Coagulopathy

Relevance to patient case: not relevant