Phase 2 Trial of Apatinib Mesylate in Locally Advanced/Metastatic Differentiated Thyroid Carcinoma

The Effectiveness and Safety of Apatinib Mesylate in Locally Advanced/Metastatic Differentiated Thyroid Carcinoma: a Phase 2 Trial.

This is a non-randomized, phase II, open label study of Apatinib Mesylate in patients with with locally advanced or metastatic differentiated thyroid carcinoma (DTC). The purpose of this study is to evaluate the efficacy and safety of apatinib in patients with locally advanced or metastatic differentiated thyroid carcinoma.

Study Overview

• Status: Unknown
• Conditions: Differentiated Thyroid Carcinoma
• Intervention / Treatment: Drug: Apatinib Mesylate

Detailed Description

At present, multiple anti-angiogenesis drugs for thyroid cancer of clinical research are ongoing worldwide, and most of which achieved fairly good therapeutic effect. To date, sorafenib has been approved for the treatment of radioactive iodine refractory DTC. Apatinib is a highly selective VEGFR2 inhibitor that reduces the angiogenesis of tumor efficiently, and had been proven to be effective in many solid tumors. In this study, the investigators aim to further explore the efficacy and safety of apatinib in locally advanced or metastatic differentiated thyroid carcinoma.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Recruiting
      • Tianjin Medical University Cancer Institute and Hospital
      • Contact: Xiangqian Zheng, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Informed consent.
2. Histopathology confirmed locally advanced or metastatic differentiated thyroid carcinoma, with measurable lesions (RECIST 1.1).
3. Age:18-75 years, ECOG（Eastern Cooperative Oncology Group） Score:0-2, Expected survival period ≥ 3 months.

4. Patients with disease progression which was confirmed by imaging in 18 months, and meet any one of the following four:

   1. The tumor invades important organs, and cannot be resectted completely, the remnant thyroid tissue is extensive and not suitable for further iodine treatment.
   2. Lesions have no iodine affinity.
   3. The cumulative dose of RAI (radioactive iodine) ≥ 600mCi or 22GBq.
   4. Patients with disease progression confirmed by radiological examination within 18 months of last RAI.

5. Patients general condition meeting the following:

   Haemoglobin (HBG) ≥ 90 g/L, neutrophil count (ANC) ≥ 1.5×109/L, platelet count (PLT) ≥ 80×109/L, total bilirubin (TBIL)< 1.5×ULN (upper limit of normal), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5×ULN (ALT and AST < 5×ULN if have liver metastasis), SCr (serum creatinine) <1.5×ULN, left ventricular ejection fraction ≥ 50% of normal.

6. Past history of less than one kind of tyrosine kinase inhibitor.
7. Pregnancy test (serum or urine) has to be performed in woman of childbearing age within 7 days before enrolment and the test result must be negative. Patients enrolled should take appropriate contraceptive measures during the study until the 6th month post the last administration of study drug. For male participants, (previous surgical sterilization accepted), agreement to take appropriate methods of contraception during the study until the 6th month post the last administration of study drug is required.

Exclusion Criteria:

1. Patients with past apatinib treatment or have received two or more small molecular TKI (Tyrosine Kinase Inhibitor) drugs.
2. Patients accepted external beam radiation therapy or iodine - 131 therapy in recent three months, or patients plan to receive the other systemic anti-tumor treatment during the study.
3. Patient with history of another malignant disease within past 5 years, cervical carcinoma in situ, non melanoma skin cancer and superficial bladder tumor are spared.
4. Patients without unrelieved toxicity reaction above CTCAE grade, neurotoxicity and hair loss due to oxaliplatin are spared.
5. Preconditions that impair successful oral medication intake (such as inability to swallow, chronic diarrhea).
6. Patients with pleural effusion or ascites that lead to respiratory syndrome (above CTCAE grade 2).
7. Patients with severe systemic diseases that might impair cardiac function, et al.
8. Patients accepted major surgery、incision biopsy or obvious traumatic injury in 28 days before the study.
9. Patients with physical signs or medical history of bleeding.
10. Patients with thromboembolism event in 6 months.
11. Patients with history of aneurysm.
12. Patients with epilepsy which needs medication.
13. Patients with history of psychiatric drug abuse or have a mental disorder.
14. Patients with history of disease in peripheral nervous system, muscle strength under level 3.
15. Attended other antitumor drug clinical trials or other ongoing clinical subjects within 4 weeks.
16. According to the researcher's judgment, there is other possible serious condition that endanger the safety of patients.

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: Experitmental; Continuous oral intake of Apatinib Mesylate (500mg), once a day, until progression of disease or severe adverse effect.	Drug: Apatinib Mesylate; oral intake of Apatinib Mesylate 500mg once a day until progression of diesase or severe adverse effect; Other Names: YN968D1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
disease control rate	percentage of patients who have achieved complete response, partial response and stable disease to overall therapeutic intervention patients	within two weeks of drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression free survival	time that passes from the day the participants received the apatinib and the date on which disease progresses or the date on which the patient dies, from any cause.	2 years
overall survival	percentage of patients who are alive after a certain time period after they were treated	2 years
objective response rate	percentage of patients who have achieved complete response and partial response to overall therapeutic intervention patients	2 weeks

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital
• Investigators: Study Chair: Ming Gao, MD, Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2017
• Primary Completion (Anticipated): January 31, 2019
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: May 24, 2017
• First Submitted That Met QC Criteria: May 24, 2017
• First Posted (Actual): May 30, 2017

Study Record Updates

• Last Update Posted (Actual): May 30, 2017
• Last Update Submitted That Met QC Criteria: May 24, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: locally advanced differentiated thyroid carcinoma; radioiodine refractory thyroid carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Carcinoma; Thyroid Diseases; Thyroid Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: AHEAD-HBT001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No