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.
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
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
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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. 2. Serum thyroglobulin levels. 3. RECIST criteria
Johannes W Smit, MD, PhD
Leiden Universty Medical Center
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)