Gland and Hormone Related Diseases

All Conditions

Neoplasms

Rare Diseases

Thyroid Diseases

Thyroid Neoplasms

Thyroid Carcinoma, Anaplastic

Carcinoma

Endocrine System Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Anaplastic Thyroid Cancer

Thyroid Cancer, Medullary

Antineoplastic Agents

All Drugs and Chemicals

Sorafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

sorafenib

Marcia S Brose, MD PhD

The goal of this study is to determine the activity of sorafenib in patients with advanced (metastatic or recurrent) thyroid cancer.

Phase II Trial of Sorafenib (Nexavar) in Patients With Advanced Thyroid Cancer

Phase II Study of BAY 43-9006 in Patients With Metastatic Thyroid Cancer

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

This is the result of the Kaplan Meier analysis of all patients treated with sorafenib

University of Pennsylvania

Associate Professor

This is a single arm study.

sorafenib: 400mg PO BID daily

Age, Continuous

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

United States

Region of Enrollment

DIfferentiated

Poorly Differentiated

Medullary

Anaplastic

Histology subtype

ECOG Performance Status 0

ECOG Performance Status 1

Eastern Cooperative Oncology Group (ECOG) performance status is a well known classification system for patient performance status. The scale goes from 0 to 4. With 0 being fully active and functional and a 4 being 100% bedridden.

ECOG Performance Status at Baseline

Four patients were deemed ineligible as a result of inadequate CBC and the establishment of an alternative diagnosis resulting from secondary pathology review.

Dr. Marcia Brose

Differentiated

Poorly Differenitated

Responses were calculated by total enrolled to each group by histologic subtype.

To Determine the Efficacy (Best Response) of BAY 43-9006 (Objective Response Rate and Stable Disease) in Patients With Metastatic Thyroid Carcinoma.

Progression Free Survival For Entire Study (55 Total Patients)

Of the 59 patients that were consented, four patients were deemed ineligible as a result of inadequate CBC and the establishment of an alternative diagnosis resulting from secondary pathology review. Therefore the total number of patients analyzed going forward was 55.

Median Progression Free Survival in Patients Receiving BAY 43-9006 (Sorafenib).

Overall Study

Patients with ascertained metastatic differentiated thyroid cancer will be studied with FDG PET, CT, and for genetic characterization. 100 MBq of 124-I are administered for blood and PET lesion dosimetry.

According Jentzen et al, good efficacy (Tumour Control Probability \> 80%) is obtained with absorbed dose higher than 80 Gy to soft tissue metastases, and \> 650 Gy to bone metastases. These values ae pursued with the limit of 2 Gy to blood.

Only soft tissue lesions will be considered as target for the calculation of the complete response rate.

However, for ethical reasons, therapeutic activity will be chosen in order to be effective both on soft tissue and bone lesions. Patients with too low predicted lesion absorbed dose even administering the Maximum Tolerable Activity (2 Gy to blood) will exit the protocol to receive the standard of care.

124-I blood and lesion dosimetry will be used to optimize the 131-I therapeutic activity. Both 124-I and 131-I administration will be performed after hormon withdrawal.

Primary tumour tissue and circulating miRNA will be analyzed to check the genetic status.

Radioiodine optimized therapy

Ettore Seregni, MD

Daria Scienza, MD

Matteo Salgarello, MD

Laura Olivari, MD

Marco Maccauro, MD

Valentina Fuoco, MD

Carlo Chiesa, PhD

Failure of conventional radioiodine therapy of metastatic differentiated thyroid cancer could be explained by:

* a suboptimal therapeutic approach, based on the administration of empirically fixed amount of radioactivity
* the presence of lesions with impaired iodine uptake, due to the expression of specific mutations

The study aims to:

* optimize therapy with pre-treatment 124-I blood and lesion dosimetry
* collect genetic data to check if specific mutations and/or miRNA over-expression could be related to low iodine uptake or to radioresistance

TRIAL DESIGN

This is a one-stage, phase II, single-arm, bi-centric study. Enrollment centres are the Istituto Nazionale Tumori in Milan, and the Sacro Cuore Don Calabria Hospital in Negrar, close to Verona. Both centres are located in North Italy. 124-I is produced by cyclotron in Negrar Radiopharmacy unit, while high-activity 131-I therapy will be delivered in Milan.

Patients with ascertained metastatic differentiated thyroid cancer are studied with FDG PET and CT. 124-I blood and lesion PET dosimetry is used to optimize the 131-I therapeutic activity. The same 124-I PET scans are repeated 6 months after therapy as response assessment. 124-I and 131-I administration are performed after hormon withdrawal.

Primary tumour tissue and circulating miRNA will be analyzed to check the genetical features.

According to 124-I dosimetric PET data published by Jentzen et al, good efficacy (Tumour Control Probability \> 80%) is obtained with absorbed dose \> 80 Gy to soft tissue metastases, and \> 650 Gy to bone metastases. Seen this difference, only soft tissue lesions are considered as target for the calculation of the complete response rate.

However, for ethical reasons, therapeutic activity will be chosen in order to be effective both on soft tissue and bone lesions. Patients with too low predicted lesion absorbed dose even administering the Maximum Tolerable Activity (2 Gy to blood) will exit the protocol to receive the standard of care.

PRIMARY END-POINT

Evaluation of complete response (CR) rate on soft tissue metastases 6 months after treatment, or later. The best response will be considered.

SECONDARY END-POINTS

Assessment of:

* acute toxicity rate and severity
* the association among pre-treatment glucose metabolism, 124-I uptake and therapy response
* the association among genetic mutations (BRAF V600E, TERT promoter, others) on thyroid cancer tissue, pre- and post-treatment miRNA expression, pre- and post-treatment glucose metabolism, iodine uptake, and 131-I therapy response

SAMPLE SIZE AND POPULATION

By considering a complete response (CR) rate in patients of soft tissue metastases after fixed activity approach as published by Klubo-Gwiezdzinska et al and by assuming an increment of 15% in CR rate after dosimetry-based administration, 46 evaluable patients will be required to test the above hypotheses.

Metastatic Thyroid Cancer Therapy Optimization With 124I PET Dosimetry

Personalized Therapy of Metastatic Thyroid Cancer: Biological Characterization and Optimization With 124I PET Dosimetry

The frequece and the grade of sialoadenitis as well as the occurrence of xerostomia will be reported as adverse event, as well as hematological toxicity nadir.

Evaluation of complete response (CR) rate on soft tissue metastases 6 months after treatment, or later. The best response will be considered.

RECIST 1.1 Evaluation of the best response rate on soft tissue metastases

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase II Trial of Sorafenib (Nexavar) in Patients With Advanced Thyroid Cancer	NCT00654238	Metastatic Diff... Metastatic Poor... Metastatic Anap... Metastatic Medu...	sorafenib	18 Years -	University of Pennsylvania
Metastatic Thyroid Cancer Therapy Optimization With 124I PET Dosimetry	NCT05299437	Metastatic Diff...	Radioiodine opt...	18 Years -	Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Phase II Trial of Sorafenib (Nexavar) in Patients With Advanced Thyroid Cancer	NCT00654238	Metastatic Diff... Metastatic Poor... Metastatic Anap... Metastatic Medu...	sorafenib	18 Years -	University of Pennsylvania
Phase II Trial of Sorafenib (Nexavar) in Patients With Advanced Thyroid Cancer	NCT00654238	Metastatic Diff... Metastatic Poor... Metastatic Anap... Metastatic Medu...	sorafenib	18 Years -	University of Pennsylvania

Spots Global Cancer Trial Database for metastatic differentiated thyroid cancer