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

Primary Purpose

Metastatic Differentiated Thyroid Cancer

Status
Recruiting
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Radioiodine optimized therapy
Sponsored by
Carlo Chiesa
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Differentiated Thyroid Cancer focused on measuring Thyroid cancer, dosimetry, 124-I, therapy optimization

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Nuclear Medicine, Ospedale Sacro Cuore - Don CalabriaRecruiting
  • Nuclear Medicine, Fondazione IRCCS Istituto Nazionale TumoriRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Optimized therapy

Arm Description

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.

Outcomes

Primary Outcome Measures

Response
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

Secondary Outcome Measures

Association between presence/absence of metastatic pre-treatment FDG uptake and response
Statistical tests will be applied to test the significance of the association.
Association between the presence/absence of specific mutations in neoplastic thyroid tissue and response
Statistical tests will be applied to test the significance of the association.
Association between circulating miRNA deregulation and response
Statistical tests will be applied to test the significance of the association.
Progression Free Survival interval (PFS) [months] from the first iodine treatment.
PFS will be assessed according to the standard clinical practice
Overall Survival [months] from the first iodine treatment.
Survival status will be collected

Full Information

First Posted
March 7, 2022
Last Updated
March 18, 2022
Sponsor
Carlo Chiesa
Collaborators
Associazione Italiana per la Ricerca sul Cancro
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1. Study Identification

Unique Protocol Identification Number
NCT05299437
Brief Title
Metastatic Thyroid Cancer Therapy Optimization With 124I PET Dosimetry
Acronym
131THEROPT124
Official Title
Personalized Therapy of Metastatic Thyroid Cancer: Biological Characterization and Optimization With 124I PET Dosimetry
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 12, 2021 (Actual)
Primary Completion Date
March 30, 2024 (Anticipated)
Study Completion Date
September 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Carlo Chiesa
Collaborators
Associazione Italiana per la Ricerca sul Cancro

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Differentiated Thyroid Cancer
Keywords
Thyroid cancer, dosimetry, 124-I, therapy optimization

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Optimized therapy
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Radioiodine optimized therapy
Intervention Description
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.
Primary Outcome Measure Information:
Title
Response
Description
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
Time Frame
6 months, repeated through study completion, an average of 2 year
Secondary Outcome Measure Information:
Title
Association between presence/absence of metastatic pre-treatment FDG uptake and response
Description
Statistical tests will be applied to test the significance of the association.
Time Frame
6 months, repeated through study completion, for an average of 2 year
Title
Association between the presence/absence of specific mutations in neoplastic thyroid tissue and response
Description
Statistical tests will be applied to test the significance of the association.
Time Frame
6 months, repeated through study completion, for an average of 2 year
Title
Association between circulating miRNA deregulation and response
Description
Statistical tests will be applied to test the significance of the association.
Time Frame
6 months, repeated through study completion, for an average of 2 years
Title
Progression Free Survival interval (PFS) [months] from the first iodine treatment.
Description
PFS will be assessed according to the standard clinical practice
Time Frame
every 6 months or more frequently, through study completion, for an average of 2 years
Title
Overall Survival [months] from the first iodine treatment.
Description
Survival status will be collected
Time Frame
At the end of the study, an average of 2 years
Other Pre-specified Outcome Measures:
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Description
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.
Time Frame
Through study completion, an average of 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ettore Seregni, MD
Phone
+39 02 2390
Ext
3320
Email
ettore.seregni@istitutotumori.mi.it
First Name & Middle Initial & Last Name or Official Title & Degree
Daria Scienza, MD
Phone
+39 02 2390
Ext
2220
Email
daria.scienza@istitutotumori.mi.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carlo Chiesa, PhD
Organizational Affiliation
Nuclear Medicine, Fondazione IRCCS Istituto Nazionale Tumori
Official's Role
Principal Investigator
Facility Information:
Facility Name
Nuclear Medicine, Ospedale Sacro Cuore - Don Calabria
City
Negrar
State/Province
Verona
ZIP/Postal Code
37129
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Matteo Salgarello, MD
Phone
+39 045 601
Ext
4611
Email
matteo.salgarello@sacrocuore.it
First Name & Middle Initial & Last Name & Degree
Laura Olivari, MD
Phone
+39 333 1885362
Email
laura.olivari@sacrocuore.it
Facility Name
Nuclear Medicine, Fondazione IRCCS Istituto Nazionale Tumori
City
Milan
ZIP/Postal Code
20133
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marco Maccauro, MD
Phone
+39 02 2390
Ext
2510
Email
marco.maccauro@istitutotumori.mi.it
First Name & Middle Initial & Last Name & Degree
Valentina Fuoco, MD
Phone
+39 02 2390
Ext
3887
Email
valentina.fuoco@istitutotumori.mi.it

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
21849530
Citation
Klubo-Gwiezdzinska J, Van Nostrand D, Atkins F, Burman K, Jonklaas J, Mete M, Wartofsky L. Efficacy of dosimetric versus empiric prescribed activity of 131I for therapy of differentiated thyroid cancer. J Clin Endocrinol Metab. 2011 Oct;96(10):3217-25. doi: 10.1210/jc.2011-0494. Epub 2011 Aug 17.
Results Reference
background
PubMed Identifier
28864610
Citation
Nagarajah J, Janssen M, Hetkamp P, Jentzen W. Iodine Symporter Targeting with 124I/131I Theranostics. J Nucl Med. 2017 Sep;58(Suppl 2):34S-38S. doi: 10.2967/jnumed.116.186866.
Results Reference
background
PubMed Identifier
27199362
Citation
Jentzen W, Verschure F, van Zon A, van de Kolk R, Wierts R, Schmitz J, Bockisch A, Binse I. 124I PET Assessment of Response of Bone Metastases to Initial Radioiodine Treatment of Differentiated Thyroid Cancer. J Nucl Med. 2016 Oct;57(10):1499-1504. doi: 10.2967/jnumed.115.170571. Epub 2016 May 19.
Results Reference
background
PubMed Identifier
25332440
Citation
Jentzen W, Hoppenbrouwers J, van Leeuwen P, van der Velden D, van de Kolk R, Poeppel TD, Nagarajah J, Brandau W, Bockisch A, Rosenbaum-Krumme S. Assessment of lesion response in the initial radioiodine treatment of differentiated thyroid cancer using 124I PET imaging. J Nucl Med. 2014 Nov;55(11):1759-65. doi: 10.2967/jnumed.114.144089. Epub 2014 Oct 20.
Results Reference
background

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Metastatic Thyroid Cancer Therapy Optimization With 124I PET Dosimetry

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