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Differentiated Thyroid CancerPhase 3DTCNCT03602495

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

A Phase 3 study testing Donafenib in people with Differentiated Thyroid Cancer, run by Suzhou Zelgen Biopharmaceuticals Co.,Ltd at 1 site in China.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Differentiated Thyroid Cancer
What is being tested?
Donafenib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
204 participants
Where
1 siteChina
Study dates
29 Aug 2018to 15 Jul 2021
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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 ;
  • Hemoglobin greater than or equal to 9.0g/dL
  • Adequate blood coagulation function:International Normalized Ratio(INR)≤2.
  • Adequate liver function: Bilirubin less than or equal to 1.5 x the upper limit of normal(ULN) ;Alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 2.5 x the upper limit of normal (ULN),for liver metastasis ALT and AST less than or equal to 5.0 x the upper limit of normal (ULN);
  • serum creatinine less than or equal to 1.5 x the upper limit of normal (ULN);creatinine clearance less than 50ml/min
  • Eastern Cooperative Oncology Group (ECOG) performance score (PS) of 0~2；
  • Life expectancy ≥12 weeks;
  • All females must have a negative serum or urine pregnancy test. Females of childbearing potential and male subjects who are partners of women of childbearing potential must use or their partners must use a highly effective method of contraception;
  • Voluntary provision of written informed consent and the willingness and ability to comply with all aspects of the protocol.
  • Swallow oral drugs and keep them in the body.

Who cannot join

  • 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;
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  • 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);
  • All chemotherapy or radiation-related toxicities must have resolved to less than Grade 2 severity, except alopecia neurotoxicity;
  • HIV infectious,active infection of the HCV and HBV (HBV-DNA more than 1000 copise/ml，expect the chronic asymptomatic HBV carrier);
  • Epileptic seizure being drug treatment;
  • Using the strong - acting CYP3A4 inducer(phenytoin,carbamazepine,rifampicin,rifapentine,phenobarbital) within 7 days of the first dose of study drug;
  • using biological reaction regulator(g-csf granulocyte colony stimulating factor) within 21 days of the first dose of study drug;
  • The drug abuse,medicine,psychology and social disease which may be have an effect on study result;
  • Any malabsorption disease;
  • The disease which is unstable and harm to safty and research compliance of patient;
  • Take the other clinical research treatment in the study and within 4 weeks prior to randomization.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Peking Union Medical College Hospital

    Beijing, Beijing Municipality

Other trials in China

About this study

Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 3 Study of Donafenib in Patients With Radioiodine-Refractory Differentiated Thyroid Cancer

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.

Read the detailed description

Blinded Phase: Participants will receive blinded study drug (Donafenib/placebo) in 2:1 ratio until documentation of disease progression (confirmed by independent imaging review committee), development of unacceptable toxicity, or withdrawal of consent. After having completed the primary analysis, subjects treated with Donafenib who have not experienced disease progression may request to continue open label Donafenib at the same dose, according to the clinical judgment of the investigator. Participants who discontinue treatment for any reason other than disease progression will be followed in the Blinded Phase until disease progression or start of another anticancer treatment; these participants then enter the Open label Phase for survival follow-up.

Open label Phase: Participants in the placebo arm who have disease progression confirmed by IRC could request to enter the Optional Open Label Donafenib Treatment Period and receive Donafenib treatment. Participants will receive Donafenib treatment until disease progression, development of intolerable toxicity, or withdrawal of consent. Participants who had disease progression during the blinded Phase and did not enter the Optional Open Label Donafenib Treatment Period and all participants who discontinued Donafenib treatment in the Optional Open Label Donafenib Treatment Period will enter the follow-up period. Participants will be followed for survival, and all anticancer treatments will be recorded until the time of death.

Being tested
Donafenib, Placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DonafenibDrug

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

  • PlaceboDrug

    Matching placebo Bid orally, continuously.

Study groups in NCT03602495
Study groupRoleWhat they receive
DonafenibExperimentalParticipants 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.
Receives: Drug: Donafenib
PlaceboPlacebo comparatorParticipants 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.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (4)

  1. Overall Survival (OS)

    Overall survival measured from the date of randomization until date of death from any cause.

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

  2. 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).

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

  3. Disease Control Rate(DCR)

    DCR is defined as the percentage of subjects whose best response was not Progressive Disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) (= total number of Complete Response (CR) + total number of Partial Response (PR) + total number of Stable Disease (SD); CR, PR, or SD had to be maintained for at least 28 days from the first demonstration of that rating)

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

  4. Time To Disease Progression (TTP)

    TTP was defined as the time from date of randomization to disease progression radiological. Subjects without progression at the time of analysis were censored at their last date of tumor evaluation.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jul 2018
  2. Study start29 Aug 2018
  3. Primary completion28 Feb 2021
  4. Study completion15 Jul 2021

Why it stopped: Based on IDMC's recommendations during the interim analysis"the trial has reached the goal of early termination of the trial". the sponsor communicating with CDE, CDE agreed to unblind the trial and submit a NDA.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
204 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03602495
Sponsor's protocol ID
ZGDD3
Acronym
DTC
Status last verified
Nov 2021
First submitted
18 Jul 2018
Last updated
13 Dec 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 39924483

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Donafenib in people with Differentiated Thyroid Cancer, run by Suzhou Zelgen Biopharmaceuticals Co.,Ltd at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 13 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Based on IDMC's recommendations during the interim analysis"the trial has reached the goal of early termination of the trial". the sponsor communicating with CDE, CDE agreed to unblind the trial and submit a NDA.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) (time frame: Date of randomization to the date of disease progression or death (whichever occurred first) or up to approximately 3 years.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03602495, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2021.

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