BRAF V600E and Redifferentiation Therapy in Radioiodine-refractory Papillary Thyroid Cancer

Completed

• Conditions: Thyroid Cancer
• Interventions: Drug: Redifferentiation with retinoid acid

• Registration Number: NCT03363347
• Lead Sponsor: Heidelberg University

Brief Summary

Papillary thyroid cancer (PTC) is the most common neoplasia in the thyroid gland. The combination of surgery, followed by radioiodine therapy (RIT) and thyroid-stimulating hormone (TSH) suppressive therapy is usually a curative option for differentiated thyroid cancer (DTC). Although DTC has a good prognosis generally, it is problematic when dedifferentiation is suspected and radioiodine refractoriness presumed. One possible therapy option for redifferentiation is the pretreatment with retinoids. From 2008 to 2014 there were 13 patients with PTC who were treated with retinoids after thyroidectomy before a further course of radioiodine. A recent study has shown that the efficacy of Selumetinib, another option for redifferentiation depends on the mutational status of the treated patient. In this retrospective study the investigators looked for a similar association between BRAF V600E and redifferentiation therapy with retinoids. As retinoids have fewer side effects compared to TKI, it is worth performing studies to assess the importance of genetic marker for the response and to estimate the chances of this specific patient collective. BRAF V600E seems to be associated with better long-term response after redifferentiation therapy with 13-cis RA in RAI-R PTC. Therefore, evaluation of BRAF mutational status prior to redifferentiation therapy could be beneficial for predicting response.

Detailed Description

Not available

Study Timeline

• Study Start: 2008-01-01
• Primary Completion: 2014-12-31
• Study Completion: 2014-12-31
• Status Verified: 2017-11
• Study First Submitted: 2017-11-20
• Study First Submitted QC: 2017-11-29
• Last Update Submitted: 2017-11-29
• Study First Posted: 2017-12-06
• Last Update Posted: 2017-12-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Radioiodine refractory papillary thyroid cancer	Redifferentiation with retinoid acid	Patients with radioiodine refractory papillary thyroid cancer who received redifferentiation therapy with retinoid acid.

Primary Outcome Measures

Name	Time	Method
Response to radioiodine therapy after redifferentiation	7 years	Redifferentiation therapy was performed using 13-cis RA (Isotretinoin, Roaccutan®) with a daily dose of orally 1,5mg/kg for up to two months. For assessment of clinical outcome of 13-cis retinoic acid treatment three parameters, tumor size, thyroglobulin levels and radioiodine uptake were considered in a graduated model.

Secondary Outcome Measures

Name	Time	Method
Parameter tumor size	7 years	Tumor size was evaluated form CT, MRI, or FDG-PET/CT imaging, comparing results before and after redifferentiation and RIT, results were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST).
Parameter thyroglobulin levels (serum Tg)	7 years	Non-stimulated serum Tg level (in ng/ml) before redifferentiation therapy was compared with the first Tg level after redifferentiation and RIT. A stable Tg level was defined as ≤10% difference.
Parameter radioiodine-uptake (RI-Uptake)	7 years	Recovery of RI-Uptake was evaluated from the post-therapy whole body scan in comparison to the lesions in CT, MRI, or FDG-PET/CT imaging before redifferentiation. Optimal uptake was defined as intensive accumulation of radioiodine in all tumor lesions. When not all lesions accumulate radioiodine or the signal was weak it was considered as suboptimal uptake.