rAd-p53 Gene Therapy for Advanced Malignant Thyroid Tumors

Study Overview
=================
Brief Summary
-----------------
This is multicenter, open-label, randomized, active-controled, phase IV study of local direct intra-tumor injection of rAd-p53 monotherapy, with concurrent radioactive iodine , or combination with surgery for treatment of advanced malignant thyroid tumors.

Detailed Description
-----------------
Primary objectives of this study is to determine the efficacy profiles of rAd-p53 intra-tumor injection alone, with with concurrent radioactive iodine, or combination with surgery for treatment of advanced malignant thyroid tumors(stage III or IV) including target lesion complete response rate (LCR) and overall target lesion response rate (OLR), response duration (RD), and progress-free survival (PFS). The secondary objectives of this study is to investigate overall response rate (OPCR) and overall complete response rate (OCR), overall survival (OS), ECOG, and safety of rAd-p53 monotherapy and combined with radioactive iodine,or surgery.

Official Title
-----------------
Open-Label, Multi-Center, Randomized, Active-Controlled, Phase 4 Study of rAd-p53 Gene Mono-Therapy, With Concurrent Radioactive Iodine , or Combination With Surgery in Subjects With Advanced Malignant Thyroid Tumors

Conditions
-----------------
Advanced Malignant Thyroid Tumors

Intervention / Treatment
-----------------
* Drug: rAd-p53 gene
* Procedure: surgery
* Drug: p53 gene therapy
* Radiation: p53 gene therapy with radioactive iodine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Advanced stages of thyroid malignant tumors (stage III and VI) At least one target tumor can be injected with study drug, the largest diameter greater than 2 cm Histologically confirmed Oral and Maxillofacial malignant tumors No prior chemotherapy, radiotherapy or biological tumor therapy in 2 weeks Age: 18-85 years old Expected to survive more 12 weeks ECOG:0-2 Neutrophils≥1.5×109/L,Platelet≥ 80×109/L, Hb≥80g/L, bilitubin≤2mg/dl,ALT and AST ≤2×institutional upper limit of normal, Cr ≤1.5×institutional upper limit of normal,coagulation tests (PTT and INR) within normal range Subject provided signed informed consent - Exclusion Criteria: Hypersensitive to study drug Tumor(s) locate very close to important blood vessels and nerves, which affect injection With a coagulation and bleeding disorder With uncontrolled, intercurrent illness including but limited to symptomatic neurological illness, symptomatic congestive heart failure, unstable angina pectoris, significant pulmonary disease or hypoxia, or psychiatric illness Local infection close to injection site or systemic infection Pregnant or lactating Principle investigator consider not suitable

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Five times of p53 gene intratumoral injection are given before surgery,then radical surgery will be conducted. | Drug: rAd-p53 gene<br>* pre-surgery p53 gene treatment: 10exp12 virus particles per 3 days for 5 times<br>|
| Active Comparator: 2<br>surgery | Procedure: surgery<br>* removal of thyroid tumor<br>|
| Experimental: 3<br>p53 gene therapy | Drug: p53 gene therapy<br>* p53 gene treatment: 10exp12 virus particles per 3 days for 10 times<br>|
| Active Comparator: 4<br>p53 gene therapy plus radioactive iodine | Radiation: p53 gene therapy with radioactive iodine<br>* p53 gene therapy with concurrent radioactive iodine pre-surgery p53 gene treatment: 10exp12 virus particles per 3 days for 10 times<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progress-free survival |  | 3 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
thyroid, p53 gene, gene therapy, malignant tumors