Restor. I-131 Upt. + Selpercatinib in RET F-P RAI-R TC

NCT05668962 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 22-018
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 6

Brief Summary

This research is being done to determine the efficacy of selpercatinib to restore radioactive iodine (I-131 NaI) uptake and allow for I-131 treatment in people with RET fusion-positive radioiodine-refractory thyroid cancer. This research study involves the study drug selpercatinib in combination with standard of care treatments, I-131 and thyrotropin alfa (rhTSH).

Conditions

Thyroid Cancer; Thyroid Carcinoma; Metastatic Thyroid Cancer; Follicular Thyroid Cancer; Unresectable Thyroid Gland Carcinoma; Papillary Thyroid Cancer

Keywords

Thyroid Cancer; Thyroid Carcinoma; Metastatic Thyroid Cancer; Follicular Thyroid Cancer; Unresectable Thyroid Gland Carcinoma; Papillary thyroid cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  RECIST v1.1 or Nies criteria in adolescents without RECIST-measurable disease The primary endpoint is best overall response (ORR) (CR and PR) at 6 months. The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started).Complete Response (CR) Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters

  6 Months

Secondary Outcomes (7)

• Number of Participants with Treatment Related Adverse Events as Assessed CTCAE v5.0

  up to 2 years

• Rate of restoration of I-131 uptake

  Initial Treatment Day 28, Re- Treatment Day 28 up 7 months

• thyroglobulin biochemical response rate

  Initial Treatment Day 1, Day 21, 3 month follow up, 6 month follow up, Re- Treatment Day 1, follow up, up to 2 years

• Progression Free Survival

  time from registration to the earlier of progression or death due to any cause up to 2 years

• Overall Survival

  time from registration to death due to any cause or censored at date last known alive up to 2 years

Study Arms (1)

SELPERCATINIB + I-131 NaI

EXPERIMENTAL

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. * Participants will be treated with Selpercatinib for 4 weeks. * In the fourth week of treatment, participants will receive a therapeutic dose of I-131 NaI. * Those participants in whom radioiodine uptake has been restored may be offered a second 4-week course of selpercatinib plus I-131 NaI treatment

Drug: Selpercatinib; Drug: Sodium Iodine I-131; Drug: rhTSH

Interventions

Selpercatinib DRUG

Selpercatinib Oral, twice daily during initial treatment period (28 Days). A second course of selpercatinib if the participant is demonstrating clinical benefit to the initial course selpercatinib and deemed clinically appropriate by the treating investigator

Also known as: Retevmo

SELPERCATINIB + I-131 NaI

Sodium Iodine I-131 DRUG

I-131 NaI, oral, is a standard treatment for all types of follicular-derived thyroid cancers, except anaplastic thyroid cancer

Also known as: I-131, I-131 NaI

SELPERCATINIB + I-131 NaI

rhTSH DRUG

RhTSH injection, dosage per protocol, timing per protocol during the initial treatment period per standard of care. Participants may receive a second course of rhTSH if the participant is demonstrating clinical benefit to the initial course rhTSH and deemed clinically appropriate by the treating investigator.

Also known as: thyrotropin alfa

SELPERCATINIB + I-131 NaI

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically- or cytologically-confirmed follicular-derived nonanaplastic thyroid cancer that is metastatic and/or unresectable AND harbors a known oncogenic RET gene fusion, performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified or equivalently accredited diagnostic laboratory.
• Tumor tissue or liquid biopsy-based next-generation sequencing (NGS), quantitative polymerase chain reaction (qPCR), and fluorescence in situ hybridization (FISH) for RET gene fusion detection will be permitted.
• Participants ≥ 18 years of age must have measurable disease, per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• \-- Participants 12 to \<18 years of age may enroll with either evaluable (i.e. anatomically visible tumor on cross sectional imaging, but tumors do not need to be \>1 cm) or measurable disease per RECIST v1.1.
• Participants should have no single tumor deposit exceeding 4.0 cm in the greatest dimension.
• Participants must have RAI-refractory disease, as defined by:
• The malignant tissue does not concentrate RAI on a whole body scan following radioiodine administration
• The tumor tissue has lost the ability to concentrate RAI on a whole body scan following radioiodine administration after previous evidence of uptake at any earlier timepoint,
• RAI is taken up in some but not all tumor deposits on a whole body scan following radioiodine administration and/or
• There is progressive disease per RECIST v1.1 despite RAI uptake on a whole body scan following radioiodine administration and/or
• For patients 12 to \<18 years of age, there is persistent anatomically visible tumor on cross sectional imaging following prior therapeutic radioiodine administration
• Participants may have received no more than a total cumulative RAI dose for treatment (not including RAI given for diagnostic purposes only) of 500 mCi (18.5 GBq).
• Participants must have asymptomatic or minimally symptomatic disease, as judged by the treating investigator. For example, patients with bone metastasis associated with mild pain not requiring narcotics for pain control, or patients with lung metastasis associated with mild cough that does not limit the participant's activities, may be considered minimally symptomatic. If confirmation of this criterion is needed, discussion with the protocol chairperson is required prior to enrollment.
• Prior external beam radiotherapy is allowed. For participants with disease limited to a prior radiotherapy field, this must be considered measurable per RECIST v1.1.
• Participants may have had no more than one prior systemic therapy for RAI-refractory thyroid cancer, including lenvatinib, sorafenib, or other MKIs. This also includes chemotherapy and/or targeted therapy administered within a clinical trial, but does not include I-131 NaI or levothyroxine. Prior RET-specific kinase inhibitor therapy, such as selpercatinib and pralsetinib, is not allowed.

You may not qualify if:

• Participants who have had chemotherapy, MKI or radiotherapy within 4 weeks.
• Participants who have had I-131 NaI treatment within 12 months.
• Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia.
• Participants who are receiving any other investigational agents.
• Participants with symptomatic CNS metastasis or lesions threatening for spinal cord compression are not eligible.
• Participants with clinically significant active cardiovascular disease or history of Torsades de pointes, history of myocardial infarction within 6 months prior to planned start of study treatment, or prolongation of the corrected QT interval by Fridericia's formula (QTcF) \>470 msec on more than one ECG during Screening. Correction of suspected drug-induced QTcF prolongation may be attempted at the investigator's discretion if clinically safe to do so.
• Participants with uncontrolled hypertension at screening, as defined by \>160/95 mm Hg.
• Participants with uncontrolled hypertension at screening may be re-screened after appropriate medical therapy for hypertension.
• Participants with an active uncontrolled systemic bacterial, viral, or fungal infection or serious ongoing intercurrent illness, such as hypertension or diabetes, despite optimal treatment, a clinical diagnosis or symptoms of interstitial lung disease, or other serious medical conditions which in the medical judgment of the investigator would prevent the patient from safely participating (screening for chronic conditions is not required).
• Participants with uncontrolled symptomatic hyperthyroidism or hypothyroidism.
• Participants with symptomatic hypercalcemia or hypocalcemia.
• Participants with active hemorrhage or at significant risk for hemorrhage.
• Participants who are taking a concomitant medication that is known to cause QTc prolongation ).
• Participants with clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the drug.
• Participants with other uncontrolled serous intercurrent illness that would interfere with the ability to proceed with study therapy.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Eli Lilly and Company: collaborator

Study Sites (6)

MedStar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Thyroid Neoplasms; Adenocarcinoma, Follicular; Thyroid Cancer, Papillary

Interventions

selpercatinib; Iodine-131; Thyrotropin Alfa

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Adenocarcinoma, Papillary

Intervention Hierarchy (Ancestors)

Thyrotropin; Pituitary Hormones, Anterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Lori J. Wirth, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lori J. Wirth, MD

CONTACT

617-724-1134; lwirth@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 20, 2022
• First Posted: December 30, 2022
• Study Start: March 1, 2023
• Primary Completion: March 1, 2025
• Study Completion: January 1, 2026
• Last Updated: December 12, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (6)