Targeted Therapy to Increase RAI Uptake in Metastatic DTC

Targeted Therapy to Increase RAI Uptake in Patients With Metastatic DifferentiatedThyroid Cancer

Papillary thyroid cancer (PTC) is a common type of differentiated thyroid cancer (DTC) in children and represents the second most common cancer in adolescent females. Recently targeted drugs that block many of the genetic drivers of DTC have become available. While Investigators know that these drugs shrink DTC tumors in many cases, the impact on radioactive iodine (RAI) avidity has not been systematically studied.

Study Overview

• Status: Recruiting
• Conditions: Pediatric Cancer; Papillary Thyroid Cancer; Differentiated Thyroid Cancer
• Intervention / Treatment: Procedure: Whole body scan

Detailed Description

This is an observational cohort study that will enroll patients with DTC metastatic to the lungs who will receive oncogene-specific targeted therapy as part of routine clinical care or a separate therapeutic clinical trial. After approximately 4 weeks of therapy, patients will have a whole body scan to determine the change in RAI-avidity of their tumor from baseline. Subsequent therapy will be at the discretion of the treating physician or according to the therapeutic trial on which the patient is enrolled.

• Study Type: Observational
• Enrollment (Estimated): 32

Contacts and Locations

• Study Contact: Name: Supriya Behl; Phone Number: 267-426-9293; Email: behls@chop.edu
• Study Contact Backup: Name: James Robinson; Phone Number: 215-590-2053; Email: robinsonj9@chop.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Not yet recruiting
      • Boston Children's Hospital
      • Principal Investigator: JUNNE KAMIHARA, MD
      • Contact: Junne Kamihara, MD
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia
      • Contact: Supriya Behl; Phone Number: 267-426-9293; Email: behls@chop.edu
      • Principal Investigator: Theodore Laetsch, MD
      • Contact: James Robinson; Phone Number: 215-590-2053; Email: robinsonj9@chop.edu
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
      • Contact: Steven Waguespack, MD
      • Principal Investigator: Steven Waguespack, MD
    • Houston, Texas, United States, 77030
      • Not yet recruiting
      • Texas Children's Hospital
      • Contact: Priya Mahajan, MD
      • Principal Investigator: Priya Mahajan, MD
  • Washington
    • Seattle, Washington, United States, 98105
      • Recruiting
      • Seattle Children's Hospital
      • Contact: Tyler Ketterl, MD, MS
      • Principal Investigator: Tyler Ketterl, MD, MS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 21 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This study will enroll children and adolescents with differentiated thyroid cancer with pulmonary metastases who are planned to receive oncogene-specific targeted therapy.

Description

Inclusion Criteria (Prospective Cohort):

1. Patients with a histologic diagnosis of differentiated thyroid cancer
2. Presence of an neurotrophic tyrosine kinase receptors (NTRK)-fusion, RET-fusion, anaplastic lymphoma kinase (ALK)-fusion, BRAF V600 mutation, BRAF-fusion or other targetable alteration identified in a Clinical Laboratory Improvement Amendments/College of American Pathologists (CLIA/CAP) laboratory

3. Anatomically evaluable disease on chest Computed tomography (CT) meeting oneo f the following criteria (obtained within 180 days of enrollment):

   1. multiple (10 or more) noncalcified solid pulmonary nodules visible on CT and/or
   2. enlarging, discrete pulmonary nodules visible on CT of any number consistent with metastatic disease

4. Patients for whom systemic therapy with an oncogene-specific kinase inhibitor is planned from commercial supply or as part of a separate therapeutic clinical trial (that does not include data sharing with this protocol)/compassionate access protocol/single patient investigational new drug (IND). Such agents include, but are not limited to:

   1. Larotrectinib, entrectinib, selitrectinib, and repotrectinib for NTRK fusions
   2. Selpercatinib and pralsetinib for RET fusions
   3. Crizotinib, lorlatinib, repotrectinib, and alectinib for ALK fusions
   4. Dabrafenib and/or trametinib for BRAF V600 mutations
   5. Oncogene-specific kinase inhibitors other than those specifically delineated above must be approved by the overall study PI prior to enrollment

Inclusion Criteria (Data Sharing Cohort):

1. Patients enrolled on other oncogene-specific targeted therapy trials who undergo whole body thyroid scan approximately 28 days after beginning targeted therapy and agree to data sharing as part of the consent process for that trial.

Exclusion Criteria (All Cohorts):

1. No prior oncogene-specific targeted therapy allowed. However, patients may enroll within 4 weeks of starting oncogene-specific therapy if a pre-therapy WBS is available. Prior therapy with non-oncogene specific multi-thyrosine kinase inhibitors (such as sorafenib, lenvatinib, and/or cabozantanib) is allowed.
2. Females who are pregnant or breastfeeding are excluded due to the potential risks of the RAI used in the WBS to the fetus/neonate.
3. Patients who require sedation/general anesthesia to complete a WBS are excluded.
4. U.S. Military Personnel are excluded due to the Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) requirements.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Prospective Cohort; Patients with differentiated thyroid cancer for whom oncogene-specific targeted therapy is planned from commercial supply or as part of a separate therapeutic trial	Procedure: Whole body scan; Patients will receive oncogene-specific molecularly targeted therapy independently of this protocol either via commercial supply of an FDA approved agent, or as part of a separate therapeutic clinical trial/compassionate use protocol/single patient investigational new drug (IND). During screening, patients will undergo a baseline RAI-whole body scan (WBS) to assess RAI-avidity of their tumor per standard of care. Following approximately 28 days of targeted therapy, the WBS will be repeated to determine whether this therapy is associated with an increase in RAI-avidity of their tumor.
Data Sharing Cohort; Patients with differentiated thyroid cancer enrolled on other oncogene-specific targeted therapy trials who undergo whole body thyroid scan approximately 28 days after beginning targeted therapy and agree to data sharing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with increased tumor RAI-avidity after receiving oncogene-specific, targeted therapy	The primary outcome measure is to determine the proportion of patients with differentiated thyroid cancer metastatic to the lungs for whom oncogene-specific, targeted therapy increases tumor RAI-avidity.	up to 5 years

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Collaborators: United States Department of Defense

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2021
• Primary Completion (Estimated): February 1, 2031
• Study Completion (Estimated): February 1, 2033

Study Registration Dates

• First Submitted: August 23, 2021
• First Submitted That Met QC Criteria: August 23, 2021
• First Posted (Actual): August 27, 2021

Study Record Updates

• Last Update Posted (Estimated): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 17, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Adenocarcinoma, Papillary; Thyroid Diseases; Thyroid Neoplasms; Thyroid Cancer, Papillary
• Other Study ID Numbers: 21-018612

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