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

February 28, 2019 updated by: Suzhou Zelgen Biopharmaceuticals Co.,Ltd

A Multicenter, Randomized, Open-Label,Phase 2 Trial of Donafenib in 131I-Refractory Differentiated Thyroid Cancer

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This phase 2 study of donafenib, an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases, is to assess efficacy and safety in patients with 131I-refractory/resistant differentiated thyroid cancer.The study is a randomised,multicentre,open-label study.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
48

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China
        • Peking Union Medical College Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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:

    1. 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.
    2. 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;
    3. 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:

    1. One or more measurable lesions that do not demonstrate iodine uptake on any radio-iodine scan
    2. 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.
    3. 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；
  • Life expectancy of at least 3 months;

  • Adequate bone marrow function:

    1. Absolute neutrophil count (ANC) greater than or equal to 1500/mm3;
    2. Platelets greater than or equal to 100,000/mm3 ;
    3. Hemoglobin greater than or equal to 9.0g/dL

  • Adequate blood coagulation function:

    1. Prothrombin time(PT)≤17s;
    2. Activated prothrombin time(APTT)≤47s;
    3. International Normalized Ratio(INR)≤2.

  • Adequate liver function:

    1. Bilirubin less than or equal to 1.5 x the upper limit of normal(ULN) ;
    2. Alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 2.5 x the upper limit of normal (ULN).
  • 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Donafenib1
This is the lower dose group. Donafenib 200mg bid
Drug: Donafenib 200mg
Donafenib is an oral multikinase inhibitor with antiproliferative and antiangiogenic effects.The arm is the lower dose one.
Other Names:
  • lower dose
ACTIVE_COMPARATOR: Donafenib2
This is the higher dose group. Donafenib 300mg bid
Drug: Donafenib 300mg
Donafenib is an oral multikinase inhibitor with antiproliferative and antiangiogenic effects.The arm is the higher dose one.
Other Names:
  • higher dose

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Objective Response Rate(ORR)
Time Frame: From randomization of the first subject until the last subject complete 24 months treatment
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Disease Control Rate(DCR)
Time Frame: From randomization of the first subject until the last subject complete 24 months treatment
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)
From randomization of the first subject until the last subject complete 24 months treatment
Overall Survival (OS)
Time Frame: From randomization of the first subject until the last subject complete 48 months treatment
OS is defined as the time from date of randomization to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact
From randomization of the first subject until the last subject complete 48 months treatment
Progression-free Survival (PFS)
Time Frame: From randomization of the first subject until the last subject complete 24 months treatment
PFS was defined as the time from date of randomization to disease progression radiological or death due to any cause, whichever occurs first. Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation.
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
Time Frame: From randomization of the first subject until the last subject complete 24 months treatment
Patients with adverse events/all patients *100%
From randomization of the first subject until the last subject complete 24 months treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Suzhou Zelgen Biopharmaceuticals Co.,Ltd

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2016

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 2, 2018

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 12, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 12, 2016

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 17, 2016

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 1, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 28, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RG01N-1271

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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