A Phase 3 Study of Donafenib in Patients With Radioiodine-refractory Differentiated Thyroid Cancer

NCT03602495 | Terminated Phase 3 DMC

• 1 other identifier: ZGDD3
• Study Type: interventional
• Target: 204
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, randomized, double-blind, placebo-controlled Phase 3 study to compare the progression free survival, overall response rate (ORR) and safety of participants treated with Donafenib 0.3g Bid by continuous oral dosing versus placebo.

Conditions

Differentiated Thyroid Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  PFS was defined as the time from the date of randomization to the date of first documentation of disease progression or death (whichever occurred first), as determined by Independent imaging review committee(IRC) using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 for the double-blind treatment period.

  Date of randomization to the date of disease progression or death (whichever occurred first) or up to approximately 3 years.

Secondary Outcomes (4)

• Overall Survival (OS)

  Date of randomization until date of death from any cause, or up to approximately 3 years.

• Objective Response Rate(ORR)

  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

• Time To Disease Progression (TTP)

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

Study Arms (2)

Donafenib

EXPERIMENTAL

Participants randomly assigned in a 2:1 ratio to receive blinded study drug (Donafenib or matching placebo) until documentation of disease progression (confirmed by IRC), development of unacceptable toxicity, or withdrawal of consent.

Drug: Donafenib

Placebo

PLACEBO COMPARATOR

Participants randomly assigned in a 2:1 ratio to receive blinded study drug (Donafenib or matching placebo) until documentation of disease progression (confirmed by IRC), development of unacceptable toxicity, or withdrawal of consent.

Drug: Placebo

Interventions

Donafenib DRUG

Donafenib 0.3g Bid orally, continuously. Dose interruptions or reductions were allowed for subjects who experienced treatment-related toxicity.

Donafenib

Placebo DRUG

Matching placebo Bid orally, continuously.

Placebo

Eligibility Criteria

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

You may qualify if:

• Male or female patients, age ≥18 years;
• Advanced or metastases thyroid cancer;
• Histologically or cytologically confirmed diagnosis of one of the following differentiated thyroid cancer (DTC) subtypes: papillary thyroid cancer, follicular thyroid cancer or Hurthle cell, poorly differentiated carcinoma;
• Disease progression within 14 months prior to randomization.
• Measurable disease according to (RECIST 1.1) and Have a minimum of one measurable lesion.
• 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)
• 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 0.5 mU/mL);
• Before 14 days prior to study entry,(before laboratory examination for 14days no blood transfusion,not use albumin and Hematopoietic Stimulating Factor),Adequate laboratory examination :
• Absolute neutrophil count (ANC) greater than or equal to 1500/ mm3;
• Platelets greater than or equal to 100,000/mm3 ;

You may not qualify if:

• Other pathologic subtypes of the thyroid, Anaplastic or medullary carcinoma of the thyroid etc;
• Prior treatment to TKI or other molecular targeted drugs；
• Subjects who have received any chemotherapy or extra radiotherapy（in addition to low dose chemotherapy for radiosensitization） within 4 weeks prior to randomization and should have recovered from any toxicity related to previous anti-cancer treatment;
• Known or suspect to TKI food allergy;in the study be allergic to drugs;
• 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 5 years;
• Major surgery, open biopsy or severe trauma within 4 weeks prior to the first dose of study drug;
• An unhealed wound, ulcer, or fracture;
• Evidence of bleeding and coagulation disorders;
• Using the antiplatelet drugs(except for a small dose of aspirin which is not more than 100mg)；
• The risk of Infiltration and bleeding of the trachea, bronchi and esophagus，not using topical treatment berore randomize;
• Bleeding of more than Grade 3 within 3 months 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;
• Cardiac arrhythmia requiring medical treatment,QTc more than 480ms；Adequately controlled blood pressure with or without antihypertensive medications, defined as BP less than 140/90 mmHg using at least 2 kinds of medicine;
• Venous or arterial thromboembolic events，cerebral blood-vessel accident，arterial thrombosis，pulmonary embolism，deep-venous thrombosis，within 6 months of the first dose of study drug;
• Active infection more than Grade 2 (any infection requiring treatment);

Sponsors & Collaborators

• Suzhou Zelgen Biopharmaceuticals Co.,Ltd: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

Location

Related Publications (1)

• 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

MeSH Terms

Interventions

donafenib

Study Officials

• Lin Yan Song, MD

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

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: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2018
• First Posted: July 26, 2018
• Study Start: August 29, 2018
• Primary Completion: February 28, 2021
• Study Completion: July 15, 2021
• Last Updated: December 13, 2021

Record last verified: 2021-11

Locations

CN (1)