Efficacy of Apatinib in Radioactive Iodine-refractory Differentiated Thyroid Cancer

NCT03048877 | Unknown Phase 3

• 1 other identifier: PUMCH-NPLA81H-Ahead-T302
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Differentiated Thyroid Cancer

Keywords

Radioactive iodine-refractory; differentiated thyroid cancer; Apatinib; anti-angiogenesis drugs

Outcome Measures

Primary Outcomes (1)

• PFS

  Progression free survival

  24 months

Secondary Outcomes (6)

• DCR

  24 months

• ORR

  24 months

• DoR

  24 months

• Changing trend of Tg and TgAb level in serum

  24 months

• OS

  24 months

Study Arms (2)

Apatinib

EXPERIMENTAL

Apatinib Mesylate Tablets

Drug: Apatinib Oral Tablet

Placebo

PLACEBO COMPARATOR

Placebo Tablets

Drug: Placebo Oral Tablet

Interventions

Apatinib Oral Tablet DRUG

Apatinib Mesylate Tablets

Apatinib

Placebo Oral Tablet DRUG

Placebo Oral Tablet

Placebo

Eligibility Criteria

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

You may qualify if:

• Aged after 18 years (18 is included).
• 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).
• 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);
• 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;
• Eastern Cooperative Oncology Group（ECOG）Performance Status（PS） :0-2.

You may not qualify if:

• Other thyroid cancer histological subtypes (such as medullary carcinoma, lymphoma or sarcoma).
• Received VEGFR inhibitor (such as vandetanib, cabozantinib, lenvatinib, sunitinib, sorafenib, etc.) treatment within 1 months.
• 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.
• Factors that could have an effect on oral medication (such as inability to swallow, nausea, vomiting, chronic diarrhea and intestinal obstruction).
• 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.
• Abnormal Coagulation (INR\>1.5、APTT\>1.5 UNL), with tendency of bleed.
• Disposition evidence of thrombosis/bleeding in 2 month (despite severity), hemoptysis in 2 months (bright red blood, 1/2 teaspoon).
• Arterial /venous thromboembolic events, such as cerebrovascular accident, deep vein thrombosis and pulmonary embolism in the past 12 months.
• Factors that could received radiotherapy or major surgery for anti - thyroid cancer in the past 28 days.
• Factors that could received surgery (allows the full-recovery wound) or active hemorrhage, ulceration, intestinal perforation or intestinal obstruction in the past 28 days.
• Uncontrolled infection.
• Pregnant or lactating women.
• Disposition evidence of depressive disorder (HAMD score ≥17).
• Other conditions regimented at investigators' discretion.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (2)

Nanjing PLA 81 Hospital

Nanjing, Jiangsu, China

Location

Peking Union Medical College Hospital

Beijing, 100730, China

Location

Related Publications (3)

• Sun D, Zhang X, Jin X, Shi C, Sun Y, Zhang Y, Liang J, Lin Y. BRAFV600E mutation is associated with better prognoses in radioactive iodine refractory thyroid cancer patients treated with multi-kinase inhibitors: a retrospective analysis of registered clinical trials. Thyroid Res. 2025 Feb 10;18(1):5. doi: 10.1186/s13044-025-00223-0.

  PMID: 39924483 DERIVED

• Zhu Y, Liu K, Wang K, Peng L. Vascular Endothelial Growth Factor Receptor Inhibitors in Chinese Patients With Advanced Radioactive Iodine-Refractory Differentiated Thyroid Cancer: A Network Meta-Analysis and Cost-Effectiveness Analysis. Front Endocrinol (Lausanne). 2022 Jul 14;13:909333. doi: 10.3389/fendo.2022.909333. eCollection 2022.

  PMID: 35909569 DERIVED

• Lin Y, Qin S, Li Z, Yang H, Fu W, Li S, Chen W, Gao Z, Miao W, Xu H, Zhang Q, Zhao X, Bao J, Li L, Ren Y, Lin C, Jing S, Ma Q, Liang J, Chen G, Zhang H, Zhang Y, Zhou X, Sang Y, Hou Z. Apatinib vs Placebo in Patients With Locally Advanced or Metastatic, Radioactive Iodine-Refractory Differentiated Thyroid Cancer: The REALITY Randomized Clinical Trial. JAMA Oncol. 2022 Feb 1;8(2):242-250. doi: 10.1001/jamaoncol.2021.6268.

  PMID: 34913959 DERIVED

MeSH Terms

Interventions

apatinib

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. M.D.

Model Details: Randomized, Double-Blind, Placebo-Controlled

Study Record Dates

• First Submitted: February 3, 2017
• First Posted: February 9, 2017
• Study Start: December 1, 2016
• Primary Completion: March 25, 2020
• Study Completion: December 31, 2023
• Last Updated: April 12, 2023

Record last verified: 2023-04

Locations

CN (2)