p53 Gene Therapy for Head and Neck Malignant Tumors in Advanced Stage

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 , with concurrent radiotherapy, or combination with surgery for treatment of head and neck malignant tumors in advanced stage .

Detailed Description
-----------------
Primary objectives of this study is to determine the efficacy profiles of rAd-p53 intra-tumor injection alone, with concurrent chemotherapy, with concurrent radiotherapy, or combination with surgery for treatment of head and neck malignant tumors in advanced stage (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, radiotherapy or surgery.

Official Title
-----------------
Open-Label, Multi-Center, Randomized, Active-Controlled, Phase 4 Study of rAd-p53 Gene Therapy Combined With Chemotherapy and Radiotherapy in Treament of Head and Neck Cancer in Advanced Stage

Conditions
-----------------
Neoplasms

Intervention / Treatment
-----------------
* Drug: chemotherapy plus p53
* Drug: chemotherapy
* Radiation: radiotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Advanced stages of head and neck 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 head and neck 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: 65 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: chemo plus p53<br>chemotherapy plus p53 | Drug: chemotherapy plus p53<br>* chemotherapy plus p53<br>|
| Active Comparator: chemo only<br>chemotherapy group | Drug: chemotherapy<br>* chemotherapy<br>|
| Active Comparator: radio<br>radiotherapy | Radiation: radiotherapy<br>* radiotherapy<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy |  | 3 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
p53 gene, head and neck malignent tumors, gene therapy