Efficacy of Apatinib in Radioactive Iodine-refractory Differentiated Thyroid Cancer

A Randomized, Double-Blind, Placebo-Controlled Study of Apatinib in Locally Advanced or Metastatic Radioactive Iodine-refractory Differentiated Thyroid Cancer

Radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) is a great challenge in the treatment of thyroid cancer. Tyrosine kinase inhibitors (TKIs), like sorafenib and lenvatinib which have been approved by food and drug administration (FDA), could not be affordable for most of the Chinese patients. Apatinib is a highly selective VEGFR2 inhibitor and reduces the angiogenesis of tumor effectively, which is a proven and effective drug in many solid tumors. A phase II study aims to assess the efficacy and safety of apatinib in RAIR-DTC ,which enrolled 20 patients and 10 of them had obtained a shout-term efficacy, demonstrating the peculiar potential in treatment of RAIR-DTC. In this study, the investigators aim to further explore the efficacy and safety of apatinib in RAIR-DTC.

Study Overview

• Status: Active, not recruiting
• Conditions: Differentiated Thyroid Cancer
• Intervention / Treatment: Drug: Placebo Oral Tablet; Drug: Apatinib Oral Tablet

Detailed Description

Primary Outcome Measure: Progression free survival of apatinib in RAIR-DTC.

Secondary Outcome Measures: Disease control rate, objective response rate, duration of response, changes of Tg and TgAb level in serum, overall survival, side effects and quality of life.

• Study Type: Interventional
• Enrollment (Anticipated): 118
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Peking, China, 100730
    • Peking Union Medical College Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Nanjing PLA 81 Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged after 18 years (18 is included).
2. Locally advanced or metastatic differentiated thyroid cancer (papillary, follicular, Hurthle cells, poorly differentiated carcinoma). At least one measurable lesion (helical CT scan long diameter ≥10mm, meet the requirements of the standard Response Evaluation Criteria In Solid Tumors（RESCIST） version 1.1).
3. Disease progression within 12 months before inclusion.

4. Subjects must be 131I-refractory / resistant as defined by at least one of the following;

   • Lesions that do not demonstrate iodine uptake on any radioiodine scan;
   • Subjects received a single radioactive iodine therapy within 12 months (≥ 3.7 Giga Bequerel（GBq）[≥ 100 millicurie（mCi）]) and target lesion disease progression;
   • Every two radioactive iodine treatment interval <12 months, doses ≥ 3.7 GBq [≥100mCi], disease progress more than 12 months after at least once iodine therapy;
   • Received a total dose of radioactive iodine therapy ≥ 22.2 GBq (≥ 600 mCi);

5. Normal main organ function:

   • HB ≥ 90g / L;
   • ANC ≥1.5×109/L;
   • PLT ≥80×109/L;
   • BIL <1.5 × ULN;
   • ALT and AST <2.5 × ULN;
   • Cr≤1×ULN;
6. Eastern Cooperative Oncology Group（ECOG）Performance Status（PS） :0-2.
7. An expected survival of ≥ 3 months.
8. Pregnancy test (serum) has to be performed for woman of childbearing age within 7 days before enrolment and the test result must be negative. They shall take appropriate methods for contraception during the study until the 8th week post the last administration of study drug. For men, (previous surgical sterilization accepted), shall agree to take appropriate methods of contraception during the study until the 8th week post the last administration of study drug.
9. Patient has to voluntarily join the study and sign the Informed Consent Form for the study.
10. Good compliance is expected, according to the program requirements follow-up and recorded adverse reactions.

Exclusion Criteria:

1. Other thyroid cancer histological subtypes (such as medullary carcinoma, lymphoma or sarcoma).
2. Received VEGFR inhibitor (such as vandetanib, cabozantinib, lenvatinib, sunitinib, sorafenib, etc.) treatment within 1 months.
3. Subjects with poor-controlled arterial hypertension (systolic blood pressure> 140 mmHg and diastolic blood pressure > 90 mm Hg) despite standard medical management; coronary heart disease greater than Class II; II-level arrhythmia (including QT interval prolongation, for man ≥ 450 ms, for woman ≥ 470 ms) together with Class II cardiac dysfunction.
4. Factors that could have an effect on oral medication (such as inability to swallow, nausea, vomiting, chronic diarrhea and intestinal obstruction).
5. Subjects with high gastrointestinal bleeding risk, including the following conditions: local active ulcer lesions with positive fecal occult blood test (++); history of black stool, or vomiting blood in the past 3 months.
6. Abnormal Coagulation (INR>1.5、APTT>1.5 UNL), with tendency of bleed.
7. Disposition evidence of thrombosis/bleeding in 2 month (despite severity), hemoptysis in 2 months (bright red blood, 1/2 teaspoon).
8. Arterial /venous thromboembolic events, such as cerebrovascular accident, deep vein thrombosis and pulmonary embolism in the past 12 months.
9. Factors that could received radiotherapy or major surgery for anti - thyroid cancer in the past 28 days.
10. Factors that could received surgery (allows the full-recovery wound) or active hemorrhage, ulceration, intestinal perforation or intestinal obstruction in the past 28 days.
11. Uncontrolled infection.
12. Pregnant or lactating women.
13. Disposition evidence of depressive disorder (HAMD score ≥17).
14. Other conditions regimented at investigators' discretion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Apatinib; Apatinib Mesylate Tablets	Drug: Apatinib Oral Tablet; Apatinib Mesylate Tablets
Placebo Comparator: Placebo; Placebo Tablets	Drug: Placebo Oral Tablet; Placebo Oral Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Progression free survival	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall survival	24 months
DCR	Disease control rate	24 months
ORR	Objective response rate	24 months
DoR	Duration of response	24 months
Changing trend of Tg and TgAb level in serum	Monitor the changes of Tg and TgAb level in serum regularly ( every 2~8 weeks, and addition examinations were needed if the participants' condition changed ) and draw the relevant changing curve to monitor the change of disease.	24 months
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Record the number of participants with treatment-related adverse events as assessed by CTCAE v4.0	24 months

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Publications and helpful links

General Publications

• Foronda C, Prather S, Snowden K, Gonzalez JM, Gattamorta KA, Lee J, Gonzalez JE, Cardenas M. Asthma academy: A student nurse-led telehealth education program for low-income family caregivers of children with asthma. Nurs Open. 2022 Mar;9(2):1486-1496. doi: 10.1002/nop2.1123. Epub 2021 Dec 16.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): March 25, 2020
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: February 3, 2017
• First Submitted That Met QC Criteria: February 7, 2017
• First Posted (Estimate): February 9, 2017

Study Record Updates

• Last Update Posted (Actual): April 12, 2023
• Last Update Submitted That Met QC Criteria: April 11, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Apatinib; differentiated thyroid cancer; Radioactive iodine-refractory; anti-angiogenesis drugs
• 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: PUMCH-NPLA81H-Ahead-T302

Drug and device information, study documents

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