sorafenib as adjuvant to radioiodine therapy in non-medullary thyroid carcinoma

Conditions: Thyroid Cancer

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

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 criteria:
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