rAd-p53 Gene Therapy for Advanced Oral and Maxillofacial Malignant 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 chemotherapy , or combination with surgery for treatment of advanced oral and maxillofacial malignant tumors.

Detailed Description
-----------------
Primary objectives of this study is to determine the efficacy profiles of rAd-p53 intra-tumor injection alone, with concurrent chemotherapy, or combination with surgery for treatment of advanced oral and maxillofacial malignant 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 chemotherapy,or surgery.

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

Conditions
-----------------
Advanced Oral and Maxillofacial Malignant Tumors

Intervention / Treatment
-----------------
* Drug: p53 gene with surgery
* Procedure: surgery
* Drug: p53 with chemotherapy
* Drug: p53 gene therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Advanced stages of Oral and Maxillofacial 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: surgery plus p53 gene<br>using p53 gene therapy before surgery | Drug: p53 gene with surgery<br>* pre-surgery p53 gene treatment: 10exp12 virus particles per 3 days for 5 times<br>* Other names: no other names;|
| Active Comparator: surgery alone<br>Surgery without pre-p53 gene therapy | Procedure: surgery<br>* remove tumor surgery<br>* Other names: no other names;|
| Experimental: p53 plus chemotherapy<br>p53 gene therapy with concurrent chemotherapy | Drug: p53 with chemotherapy<br>* p53 gene treatment: 10exp12 virus particles per 3 days for 10 times Chemotherapy: standard chemotherapy<br>* Other names: no other names;|
| Experimental: p53 gene therapy alone<br>Intra-tumor injectio of rAd-p53 gene with no concurrent treatment | Drug: p53 gene therapy<br>* p53 gene treatment: 10exp12 virus particles per 3 days for 10 times<br>* Other names: no other names;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall best 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
-----------------
p53 gene, Oral and Maxillofacial, gene therapy, malignant tumors