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…
ID
Source
Brief title
Condition
- Endocrine and glandular disorders NEC
- Endocrine neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The endpoint of the study Part I 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:
a. 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
b. 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:
a. 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.
b. 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;
c. Complete response: the disappearance of all target lesions;
Secondary outcome
The endpoint of the study Part IIa is the proportion of patients with a
favorable response to Sorafenib and 6000 MBq RaI with the response in Part I as
a reference: defined as ONE OR MORE of the following criteria 6 months after
RaI therapy:
a. RaI uptake: A reduction in the number of lesions and/or quantitative RaI
uptake in target lesions as assessed by RaI scintigraphy as compared with the
diagnostic RaI scintigraphy at 6 months after initiation.
b. Serum thyroglobulin levels: The slope at linear regression of the
log-transformed serum Tg levels measured in the 6 months after RaI therapy is
statistically significantly different (more negative) than the slope during
Part I.
c. CT imaging: Tumor response at imaging according to RECIST criteria is one
class higher than during Part I. (for instance: stable disease during Part I
and partial response during Part II).
Background summary
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.
Study objective
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.
Intervention
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.
Study burden and risks
na
Postbus 9600
2300 RC Leiden
Nederland
Postbus 9600
2300 RC Leiden
Nederland
Listed location countries
Age
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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-002365-13-NL |
| CCMO | NL17727.058.07 |