Sorafenib as Adjuvant to Radioiodine Therapy in Non-Medullary Thyroid Carcinoma
- Registration Number
- NCT00887107
- Lead Sponsor
- Leiden University Medical Center
- Brief 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 32
- 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
- Pregnancy
- Other active malignancies
- Active kidney, liver or pancreatic disease or dysfunction
- Unstable angina pectoris or recent (<3 months) myocardial infarction.
- Coagulopathy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description sorafenib Sorafenib (nexavar) 30 patients with non-radioiodine avid differentiated thyroid carcinoma
- Primary Outcome Measures
Name Time Method 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 6 months
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Leiden University Medical Center
🇳🇱Leiden, Netherlands