Study of Neoadjuvant Regimen for Radioactive Iodine Treatment of Metastatic and Advanced Differentiated Thyroid Cancers (APT-01)

Evaluating the Safety and Efficacy of Radioactive Iodine (RAI) Treatment of Metastatic and Advanced Differentiated Thyroid Cancers by Pretreatment With Apatinib for the Neoadjuvant Regimen

The purpose of this study is to determine Safety and Efficacy of Radioactive Iodine (RAI) Treatment of Metastatic and Advanced Differentiated Thyroid Cancers by Pretreatment With Apatinib for the Neoadjuvant Regimen

Study Overview

• Status: Unknown
• Conditions: Metastasis; Thyroid; Apatinib
• Intervention / Treatment: Drug: Apatinib

Detailed Description

This study is design to prospectively investigate the safety and efficacy of apatinib in downsizing primary tumors and metastatic lesions in patients with metastatic and advanced differentiated thyroid cancers before RAI Treatment.

Standard treatment of thyroid cancer includes thyroidectomy, RAI treatment, and levothyroxine replacement therapy. Before RAI treatment, L-thyroxin replacement therapy should be stopped to induce TSH elevation, thereby promoting the intake of radioactive iodine in residual or metastatic lesions. However, the process of withdrawing L-thyroxin for 4-6 weeks might promote the progression of the tumor. The main hypothesis is that the use of tyrosine kinase inhibitor will reduce the tumor proliferation or metastasis rate of patients before RAI Treatment.

Apatinib is a tyrosine kinase inhibitor that selectively inhibits the vascular endothelial growth factor receptor-2. This is a single-institution, single-arm phase 2 clinical trial. Patients will receive axitinib 500mg qd for up to 12 week. Patients then will receive RAI Treatment. If the severe adverse effects discontinued study treatment prior to 12 week, the patient may also receive subsequent RAI treatment at the time of suspension. The follow-up period was followed up to assess safety and effectiveness.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Jingsu
    • Nanjing, Jingsu, China, 210006
      • Recruiting
      • Nanjing First Hospital
      • Contact: Liang Shi, PhD; Phone Number: +8618951773121; Email: langkerufeng@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The patient volunteers and signs an informed consent form.
2. age ≥18 and <99 years old;
3. Diagnosed as differentiated thyroid cancer (DTC) by histopathology;
4. surgically inoperable and/or recurrent/metastatic differentiated thyroid cancers;
5. Did not receive molecular targeting treatment; Prior RAI therapy is allowed if > 3 months prior to initiation of therapy on this protocol and evidence of progression (as defined above) has been documented in the interim.
6. There must be at least one measurable lesion (according to RECIST v1.1);
7. Physical condition ECOG PS: 0-2;
8. Expected survival time ≥ 3 months;
9. Laboratory tests meet the following criteria: Bone marrow function: absolute count of blood neutrophils (ANC) ≥1.5×109/L; platelet (PLT)≥100×109/L; hemoglobin (HB)≥90g/L; Liver function: alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ULN*2.5
10. Well controlled blood pressure prior to study entry.
11. At least one or more hypermetabolic lesions other than the neck on 18F-FDG PET scans

Exclusion Criteria:

1. Anaplastic thyroid carcinoma, thyroid lymphoma, mesenchymal tumors of the thyroid, metastases to the thyroid;
2. Previous treatment with chemotherapy for anti-thyroid cancer (allowing low-dose chemotherapy for radiation sensitization) or treatment with thalidomide or its derivatives;
3. Previous treatment with VEGFR-TKI small molecule drugs within 1 month, such as vandetanib, cabozantinib, lenvatinib, sunitinib, sorafenib, etc.;
4. Major surgery within 4 weeks prior to enrollment, or received anti-thyroid cancer radiotherapy;
5. Severe cardiovascular disease, including hypertension (BP≥140/90mmHg) uncontrolled by medical treatment, unstable angina, history of myocardial infarction, congestive heart failure>NYHA II, Marked baseline prolongation of QT/corrected QT (QTc) interval;
6. Severe infection requires intravenous antibiotic, antifungal or antiviral treatment;
7. Active hemoptysis (bright red blood of at least one-half teaspoon) in the 28 days prior to study entry;
8. Suffering from mental illness, poor compliance;
9. Pregnant women will be ineligible; breast feeding should be discontinued if the mother is treated with Apatinib;
10. Embolization and bleeding occurred within 4 weeks before enrollment;
11. Patient with a risk of gastrointestinal bleeding; abnormal coagulation function (INR > 1.5, APTT > 1.5 × ULN);
12. Arteriovenous thrombosis such as cerebrovascular accidents, deep vein thrombosis, and pulmonary embolism within 12 months prior to screening;
13. A variety of factors that affect the absorption of oral medications (such as inability to swallow, nausea and vomiting, chronic diarrhea and intestinal obstruction)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neoadjuvant arm; Patients receive Apatinib orally qd up to 12 wk.	Drug: Apatinib; 500 mg Apatinib given orally once a day for 12 wk prior to RAI (131I) treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	Number of patients achieving a complete response (CR) or partial response (PR) by Response Evaluation Criteria (RECIST v1.1 criteria) in Solid Tumors.	4 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events	This study will utilize the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 4.0 for toxicity and Serious Adverse Event reporting	Time interval from start to 3 months after completion of the therapy
Change From Baseline in Serum Thyroglobulin Levels After Treatment With RAI (131I)		Baseline, 4 weeks, 12 weeks and 1 month after RAI

Collaborators and Investigators

• Sponsor: Nanjing First Hospital, Nanjing Medical University
• Investigators: Study Director: Feng Wang, PhD MD, The First Affiliated Hospital with Nanjing Medical University

Publications and helpful links

General Publications

• Shi L, You Q, Wang J, Wang H, Li S, Tian R, Yao X, Wu W, Zhang L, Wang F, Lin Y, Li S. Antitumour effects of apatinib in progressive, metastatic differentiated thyroid cancer (DTC). Endocrine. 2022 Oct;78(1):68-76. doi: 10.1007/s12020-022-03113-9. Epub 2022 Jun 29.

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2019
• Primary Completion (Anticipated): April 10, 2020
• Study Completion (Anticipated): May 30, 2020

Study Registration Dates

• First Submitted: November 24, 2019
• First Submitted That Met QC Criteria: November 26, 2019
• First Posted (Actual): November 27, 2019

Study Record Updates

• Last Update Posted (Actual): November 27, 2019
• Last Update Submitted That Met QC Criteria: November 26, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Thyroid Diseases; Thyroid Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: wangfeng-Apatinib-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No