Effecten van Sorafenib op de effectiviteit van therapie met radioactief jodium bij niet medullair schildkliercarcinoom

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;

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).