Phase 2 Trial of Donafenib in 131I-Refractory Differentiated Thyroid Cancer

NCT02870569 | Completed Phase 2

• 1 other identifier: RG01N-1271
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Donafenib for advanced 131I-refractory/resistant differentiated thyroid cancer(DTC).

Conditions

Differentiated Thyroid Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate(ORR)

  ORR is defined as the percentage of subjects with total number of Complete Response(CR)+total number of Partial Response(PR).

  From randomization of the first subject until the last subject complete 24 months treatment

Secondary Outcomes (4)

• Overall Survival (OS)

  From randomization of the first subject until the last subject complete 48 months treatment

• Progression-free Survival (PFS)

  From randomization of the first subject until the last subject complete 24 months treatment

• Safety variables will be summarized using descriptive statistics based on adverse events collection

  From randomization of the first subject until the last subject complete 24 months treatment

• Disease Control Rate(DCR)

  From randomization of the first subject until the last subject complete 24 months treatment

Study Arms (2)

Donafenib1

EXPERIMENTAL

This is the lower dose group. Donafenib 200mg bid

Drug: Donafenib 200mg

Donafenib2

ACTIVE COMPARATOR

This is the higher dose group. Donafenib 300mg bid

Drug: Donafenib 300mg

Interventions

Donafenib 200mg DRUG

Donafenib is an oral multikinase inhibitor with antiproliferative and antiangiogenic effects.The arm is the lower dose one.

Also known as: lower dose

Donafenib1

Donafenib 300mg DRUG

Donafenib is an oral multikinase inhibitor with antiproliferative and antiangiogenic effects.The arm is the higher dose one.

Also known as: higher dose

Donafenib2

Eligibility Criteria

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

You may qualify if:

• Advanced or metastases thyroid cancer;
• Subjects must have histologically or cytologically confirmed diagnosis of one of the following differentiated thyroid cancer (DTC) subtypes: papillary thyroid cancer (PTC),follicular thyroid cancer (FTC) or Hurthle cell ;
• Measurable disease meeting the following criteria and confirmed by central radiographic review:
• At least 1 lesion of greater than or equal to 1.0 cm in the longest diameter for a non-lymph node or greater than or equal to 1.5 cm in the short-axis diameter for a lymph node which is serially measurable according to RECIST 1.1 using computerized tomography.
• Lesions that have had external beam radiotherapy (EBRT) or loco-regional therapies such as radio-frequency (RF) ablation must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion;
• Bone metastases lesion is non-measurable.
• Subjects must show evidence of disease progression within 14 months prior to signing informed consent, according to RECIST 1.1 assessed and confirmed by central radio-graphic review of CT scans.
• Subjects must be 131I-refractory / resistant as defined by at least one of the following:
• One or more measurable lesions that do not demonstrate iodine uptake on any radio-iodine scan
• One or more measurable lesions that has progressed by RECIST 1.1 within 14 months of 131I therapy, despite demonstration of radio-iodine avidity at the time of that treatment by pre-treatment scanning.
• Cumulative activity of 131I of \>600 mCi or 22 gigabequerels (GBq), with the last dose administered at least 6 months prior to study entry
• Subjects may have not received molecular targeted therapy;
• Subjects with known brain metastases who have completed whole brain radiotherapy, stereotactic radiosurgery or complete surgical resection, will be eligible if they have remained clinically stable, asymptomatic and off of steroids for one month
• Subjects must tolerate to thyroxin ,and TSH suppression (TSH less than 0.1 mU/mL);
• Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0\~2；

You may not qualify if:

• Anaplastic or Medullary carcinoma of the thyroid;
• Prior treatment to sorafenib or other molecular targeted drugs;
• Subjects who have received any chemotherapy or extra radiotherapy within 30 days prior to the first dose of study drug and should have recovered from any toxicity related to previous anti-cancer treatment;
• Major surgery within 30 days prior to the first dose of study drug;
• Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina; myocardial infarction or stroke within 6 months of the first dose of study drug, or cardiac arrhythmia requiring medical treatment;
• Active infection (any infection requiring treatment);
• Active malignancy (except for differentiated thyroid carcinoma, or definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 24 months;
• Known intolerance to any of the study drugs (or any of the excipients);
• All chemotherapy or radiation-related toxicities must have resolved to less than Grade 2 severity, except alopecia and infertility;
• Adequately controlled blood pressure with or without antihypertensive medications, defined as BP less than 140/90 mmHg using at least 2 kinds of medicine;
• Adequate renal function defined as calculated creatinine clearance less than or equal to 60 mL/min per the Cockcroft and Gault formula.

Sponsors & Collaborators

• Suzhou Zelgen Biopharmaceuticals Co.,Ltd: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

Location

Related Publications (2)

• 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

• Lin YS, Yang H, Ding Y, Cheng YZ, Shi F, Tan J, Deng ZY, Chen ZD, Wang RF, Ji QH, Huang R, Li LF. Donafenib in Progressive Locally Advanced or Metastatic Radioactive Iodine-Refractory Differentiated Thyroid Cancer: Results of a Randomized, Multicenter Phase II Trial. Thyroid. 2021 Apr;31(4):607-615. doi: 10.1089/thy.2020.0235. Epub 2020 Oct 15.

  PMID: 32907500 DERIVED

MeSH Terms

Interventions

donafenib

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2016
• First Posted: August 17, 2016
• Study Start: September 1, 2016
• Primary Completion: July 2, 2018
• Study Completion: December 1, 2018
• Last Updated: March 1, 2019

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)