Trail Evaluating Apatinib With IMRT for Inoperable or Iodine Refractory Thyroid Cancer

Study Overview
=================
Brief Summary
-----------------
To determine the efficacy and safety of intensity modulated radiation therapy combined with apatinib for inoperable or iodine refractory thyroid cancer.

Official Title
-----------------
Intensity Modulated Radiation Therapy Combined With Apatinib for Inoperable or Iodine Refractory Thyroid Cancer: A Phase II Single-arm Study

Conditions
-----------------
Thyroid Cancer

Intervention / Treatment
-----------------
* Drug: Apatinib
* Radiation: Intensity modulated radiation therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Ability to understand character and individual consequences of the clinical trial. Willing to sign the written informed consent; Informed consent must be signed before the enrollment in the trial; Aged ≥ 18 years old; Pathologically confirmed inoperable or iodine refractory thyroid cancer, or postoperative residual disease detected by imaging studies, or progression disease within 12 months before enrollment. (all with measurable disease ≥10mm according to RECIST 1.1); ECOG0-2; Adequate laboratory values within 14 dyas of enrollment to study defined as follows: N ≥ 1500/mm^3; PLT ≥ 80,000/mm^3; HB≥90g/L;total bilirubin < 1.25ULN; AST/ALT < 2.5 ULN or < 5 ULN with metastasis; SCr ≤1ULN; CCR > 50ml/min; The survival period is expected to be greater than 3 months; Willing to accept adequate contraception for patients with childbearing potential. Exclusion Criteria: Take chemotherapeutic chemotherapy (the use of low-dose chemotherapy for radiosensitization was allowed) or thalidomide and its derivative treatments; Take VEGFR-TKI within 1 month, such as vandetanib, cabozantinib, lenvatinib, sunitinib and sorafenib; Allergic to apainib; Uncontrolled high blood pressure and heart disease; Patients with gastrointestinal bleeding risk; Coagulation disorders(INR>1.5×ULNAPTT>1.5×ULN); Uroprotein positive (Uroprotein≥2+ or 24-hour urinary protein quantity >1.0g); Pregnant or lactating women.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apatinib with IMRT<br>Participants will receive apatinib (0.5g, daily) for two cycles followed by intensity modulated radiation therapy (Primary site and lymph nodes: 66 Gy/33F, metastatic site: 40-60Gy/20-30F) | Drug: Apatinib<br>* Apatinib will be used as induction therapy in experimental arm.<br>Radiation: Intensity modulated radiation therapy<br>* Intensity modulated radiation therapy will be used for patients with progression disease during induction therapy or after induction therapy.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | The time from date of randomization until date of first documented disease progression or death from any cause | 3-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Short-term treatment response rate | Number of participants responded to the therapy according to RECIST 1.1 | Three months after completion of the therapy | 
| Overall survival | Overall survival is calculated from randomization to death from any cause. | 3-year | 
| Time to Response | Time to first response to the therapy according to RECIST 1.1 | From the initial treatment to first response, up to 3 years | 
| Duration of Response | Time from the first response to the therapy to disease progression | From first response to disease progression, up to 3 years | 
| Number of participants with treatment-related adverse events as assessed by NCI CTCAE v4.03 | Incidence of acute and late toxicity | Time interval from start to 3 months after completion of the therapy | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Thyroid Cancer, Apatinib, Intensity modulated radiation therapy