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

Thyroid Cancer Clinical Trial

Official title:

Association Between BRAF V600E and Redifferentiation Therapy in Patients With Radioiodine-refractory Papillary Thyroid Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03363347
• Other study ID #: S-206/2005
• Status: Completed
• Phase: N/A
• First received: November 20, 2017
• Last updated: November 29, 2017
• Start date: January 1, 2008
• Est. completion date: December 31, 2014

Study information

• Verified date: November 2017
• Source: Heidelberg University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: December 31, 2014
• Est. primary completion date: December 31, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 24 Years to 69 Years

Eligibility

Eligible criteria for radioiodine-refractory patients included:

• PTC

• no response to former RIT

• decrease or loss of initial sufficient RI-Uptake

• redifferentiation therapy with 13-cis-RA

• available FFPE tissue.

Eligible criteria for radioiodine-sensitive patients included:

• PTC

• cured after a maximum of two RIT

• no redifferentiation therapy necessary

• available FFPE tissue.

Exclusion criteria

• DTC other than PTC

• patients lost to follow-up

• other redifferentiation therapy than retinoids

• anaplastic or medullary thyroid cancer

• benign thyroid disease, no available FFPE tissue

• more than two RITs in the control group

• insufficient clinical information.

Related Conditions & MeSH terms

• Carcinoma
• Thyroid Cancer
• Thyroid Diseases
• Thyroid Neoplasms

Intervention

Drug:
• Redifferentiation with retinoid acid
In this retrospective study, patients with radioiodine refractory papillary thyroid cancer routinely received (clinical indication, no study medication was given) retinoid acid for redifferentiation prior to further course of radioiodine therapy.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Heidelberg University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response to radioiodine therapy after redifferentiation	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.	7 years
Secondary	Parameter tumor size	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).	7 years
Secondary	Parameter thyroglobulin levels (serum Tg)	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.	7 years
Secondary	Parameter radioiodine-uptake (RI-Uptake)	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.	7 years