Study of Anlotinib in Patients With Differentiated Thyroid Cancer(ALTER01032)

Study Overview
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Brief Summary
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The purpose of this study is to compare the effects and safety of Anlotinib with placebo in patients with Differentiated Thyroid Cancer.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Multicenter Clinical Trial to Compare the Efficacy and Safety of Anlotinib Versus Placebo in Patients With 131I-Refractory Differentiated Thyroid Cancer(ALTER01032)

Conditions
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Differentiated Thyroid Cancer

Intervention / Treatment
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* Drug: Anlotinib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated informed consent Histological documentation of Differentiated Thyroid Cancer ,With measurable disease (using RECIST1.1) ECOG PS:0-1,Life expectancy of more than 6 months Subjects must be 131I-refractory / resistant as defined by at least one of the following: Lesions that do not demonstrate iodine uptake on any radioiodine scan Cumulative activity of 131I of >600 mCi or 22 gigabequerels (GBq) Lesion that demonstrate iodine uptake on any radioiodine scan,but has progressed by RECIST 1.1 within 18 months of 131I therapy main organs function is normal Exclusion Criteria: Prior treatment with Anlotinib or VEGFR-targeted therapies(such as Vandetanib,Cabozantinib,Lenvatinib,Sunitinib,Sorafenib etc.) Subjects received radiotherapy external exposure or 131I within 3 months prior to the first dose of study drug or plan to be received any anti-cancer treatment during study Patients suffering from other malignancies currently or within 5 years, except for cured cervical carcinoma in situ, non-melanoma skin cancers and superficial bladder cancer [ Ta (non-invasive carcinoma), Tis (carcinoma in situ) and T1 (carcinoma invasion into lamina propria) ] CTCAE(4.0) Grade 1 or higher non-remission toxicity induced by any other previous treatments，excluding alopecia and Grade 2 or lower neurotoxicity induced by oxaliplatin Patients with factors that could affect oral medication (such as dysphagia etc.) Patients with pleural effusion or ascites, causing respiratory syndrome (CTCAE Grade 2 or higher dyspnea [Grade 2 dyspnea refers to Shortness of breath with a small amount of activities, affecting Instrumental activities of daily life]) Patients underwent major surgical treatment，open biopsy or significant traumatic injury within 28 days prior to assignment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anlotinib<br>Anlotinib QD po and it should be continued until disease progression or intolerable toxicity or patients withdrawal of consent.Subjects with confirmation of disease progression by independent imaging review, while receiving blinded study drug may request to receive open label Anlotinib and enter the Optional Open Label Anlotinib Treatment Period of the Extension Phase. Subjects who request to receive open label Anlotinib(at the time of confirmed progression) will be informed whether they received placebo or Anlotinib during the period of blinded study drug administration. Subjects who received Anlotinib will not be eligible for the open-label phase. | Drug: Anlotinib<br>* Anlotinib p.o. qd<br>|
| Placebo Comparator: Placebo<br>Placebo QD po and it should be continued until disease progression or intolerable toxicity or patients withdrawal of consent.Subjects with confirmation of disease progression by independent imaging review, while receiving blinded study drug may request to receive open label Anlotinib and enter the Optional Open Label Anlotinib Treatment Period of the Extension Phase. Subjects who request to receive open label Anlotinib(at the time of confirmed progression) will be informed whether they received placebo or Anlotinib during the period of blinded study drug administration. | Drug: Placebo<br>* Placebo p.o. qd<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | To compare the Progression-free Survival (PFS) of subjects with Differentiated Thyroid Cancer(DTC) with Anlotinib versus Placebo. | Date of randomization to the date of disease progression (measured every 6 weeks) or death (whichever occurs first) as determined by blinded independent imaging review(assessed up to 24 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | To compare Overall Response Rate (ORR) (Complete and Partial Responses, CR and PR) of subjects treated with Anlotinib versus Placebo. | Date of randomization to the date of disease progression (measured every 6 weeks) or death (assessed up to 24 months) |