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Donafenib in 131I-Refractory Differentiated Thyroid Cancer

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ClinicalTrials.gov Identifier: NCT03602495
Recruitment Status : Recruiting
First Posted : July 26, 2018
Last Update Posted : October 22, 2019
Sponsor:
Information provided by (Responsible Party):
Suzhou Zelgen Biopharmaceuticals Co.,Ltd

Tracking Information
First Submitted Date  ICMJE July 18, 2018
First Posted Date  ICMJE July 26, 2018
Last Update Posted Date October 22, 2019
Actual Study Start Date  ICMJE June 26, 2018
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 18, 2018)
Progression-free Survival [ 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 18, 2018)
  • Overall Survival [ 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
  • 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).
  • 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)
  • Time To Disease Progression (TTP) [ Time Frame: From randomization of the first subject until the last subject complete 24 months treatment ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Donafenib in 131I-Refractory Differentiated Thyroid Cancer
Official Title  ICMJE A Multicenter, Randomized, Double-Blind,Placebo-controlled,Phase 3 Trial of Donafenib in 131IRefractory Differentiated Thyroid Cancer
Brief Summary Donafenib for advanced 131I-refractory/resistant differentiated thyroid cancer(DTC).
Detailed Description This phase 3 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,double-blind,placebo-controlled,study.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Differentiated Thyroid Cancer
Intervention  ICMJE
  • Drug: Donafenib
    after continuing to intolerance or progress in double blind treatment period,for progress but tolerance into open therapy period for Donafenib evaluated by investigator
    Other Name: treatment drug
  • Drug: Placebo
    after continuing to intolerance or progress in double blind treatment period,for progress but tolerance into open therapy period for Donafenib evaluated by investigator
    Other Name: Placebo for Donafenib
Study Arms  ICMJE
  • Experimental: Donafenib
    Donafenib 300mg bid for each 28 days cycle.
    Intervention: Drug: Donafenib
  • Placebo Comparator: Placebo
    Placebo 300mg bid for each 28 days cycle.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 18, 2018)
204
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2021
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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,poorly differentiated carcinoma ;
  • 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.
  • 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 1.5cm 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 locoregional 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 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)
  • 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 :

    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
    4. Adequate blood coagulation function:International Normalized Ratio(INR)≤2.
    5. 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);
    6. serum creatinine less than or equal to 1.5 x the upper limit of normal (ULN);creatinine clearance less than 50ml/min
  • Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0~2;
  • Life expectancy of at least 3 months;
  • 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

Exclusion Criteria:

  • Other pathologic subtypes of the thyroid,undifferentiated carcinoma,medullary carcinoma,lymphoma and sarcoma 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 30 days prior to the first dose of study drug 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);
  • 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 of the first dose of study drug;
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Lin Yan Song, MD 13671116837 linys@pumch.cn
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03602495
Other Study ID Numbers  ICMJE ZGDD3
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Suzhou Zelgen Biopharmaceuticals Co.,Ltd
Study Sponsor  ICMJE Suzhou Zelgen Biopharmaceuticals Co.,Ltd
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Lin Yan Song, MD Peking Union Medical College Hospital
PRS Account Suzhou Zelgen Biopharmaceuticals Co.,Ltd
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP