Metastatic Thyroid Cancer Therapy Optimization With 124I PET Dosimetry (131THEROPT124)

March 18, 2022 updated by: Carlo Chiesa

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

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histo-pathological diagnosis of DTC
  • At least one documented non surgically-curable soft-tissue metastasis previously untreated
  • ECOG performance status = 0 - 1
  • Life expectancy > 6 months
  • Females of childbearing age must have negative serum pregnancy test prior to registration and agree to use birth control throughout the study and for 6 months after completion of therapy
  • Preserved hematologic and renal function (hemoglobin > 10 g/dL; WBC > 3500/uL; neutrophils > 50%; PLT > 100000/uL; albumin ≥ 2.5 g/dL; creatinine ≤ 2 mg/dL)
  • Signed informed consent

Exclusion Criteria:

  • All lesions surgically resectable
  • Minimal lymph nodal disease (diameter < 1 cm, up to 2 nodes)
  • Patient with skeletal metastases only
  • Lung diffuse miliary micro-metastases
  • Ongoing pregnancy
  • Breast-feeding (enrollment could be considered after suspension)
  • Refusal of male and female patients to use an effective contraception method during the study and for 6 months after completion of protocol therapy
  • Impossibility to undergo follow-up procedures
  • Presence of medical, psychiatric or surgical condition, not adequately controlled by treatment, which would likely affect subjects' ability to complete the protocol
  • Assumption of any anti-tumor therapy including chemotherapy, biological or investigational drug treatments
  • Assumption of any myelotoxic drugs
  • Previous or concomitant assumption of Amiodarone
  • Any other oncologic disease that required treatment in the last 5 years.
  • Participation in a clinical trial in which an investigational drug was administered within 30 days or 5 half-lives prior to the study drug.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Optimized therapy

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.
Drug: Radioiodine optimized therapy

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response
Time Frame: 6 months, repeated through study completion, an average of 2 year

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
6 months, repeated through study completion, an average of 2 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Association between presence/absence of metastatic pre-treatment FDG uptake and response
Time Frame: 6 months, repeated through study completion, for an average of 2 year
Statistical tests will be applied to test the significance of the association.
6 months, repeated through study completion, for an average of 2 year
Association between the presence/absence of specific mutations in neoplastic thyroid tissue and response
Time Frame: 6 months, repeated through study completion, for an average of 2 year
Statistical tests will be applied to test the significance of the association.
6 months, repeated through study completion, for an average of 2 year
Association between circulating miRNA deregulation and response
Time Frame: 6 months, repeated through study completion, for an average of 2 years
Statistical tests will be applied to test the significance of the association.
6 months, repeated through study completion, for an average of 2 years
Progression Free Survival interval (PFS) [months] from the first iodine treatment.
Time Frame: every 6 months or more frequently, through study completion, for an average of 2 years
PFS will be assessed according to the standard clinical practice
every 6 months or more frequently, through study completion, for an average of 2 years
Overall Survival [months] from the first iodine treatment.
Time Frame: At the end of the study, an average of 2 years
Survival status will be collected
At the end of the study, an average of 2 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame: Through study completion, an average of 2 years
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.
Through study completion, an average of 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Carlo Chiesa

Collaborators

Associazione Italiana per la Ricerca sul Cancro

Investigators

  • Principal Investigator: Carlo Chiesa, PhD, Nuclear Medicine, Fondazione IRCCS Istituto Nazionale Tumori

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

May 12, 2021

Primary Completion (ANTICIPATED)

March 30, 2024

Study Completion (ANTICIPATED)

September 30, 2024

Study Registration Dates

First Submitted

March 7, 2022

First Submitted That Met QC Criteria

March 18, 2022

First Posted (ACTUAL)

March 29, 2022

Study Record Updates

Last Update Posted (ACTUAL)

March 29, 2022

Last Update Submitted That Met QC Criteria

March 18, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AIRC 21939

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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