Trial Information

Sorafenib as Adjuvant to Radioiodine Therapy in Non-Medullary 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