rAd-p53 Gene Therapy for Advanced Oral and Maxillofacial Malignant Tumors

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.

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.

• Drug: p53 gene with surgery
  pre-surgery p53 gene treatment: 10exp12 virus particles per 3 days for 5 times
  Other Name: no other names
• Procedure: surgery
  remove tumor surgery
  Other Name: no other names
• Drug: p53 with chemotherapy
  p53 gene treatment: 10exp12 virus particles per 3 days for 10 times Chemotherapy: standard chemotherapy
  Other Name: no other names
• Drug: p53 gene therapy
  p53 gene treatment: 10exp12 virus particles per 3 days for 10 times
  Other Name: no other names

• Experimental: surgery plus p53 gene
  using p53 gene therapy before surgery
  Intervention: Drug: p53 gene with surgery
• Active Comparator: surgery alone
  Surgery without pre-p53 gene therapy
  Intervention: Procedure: surgery
• Experimental: p53 plus chemotherapy
  p53 gene therapy with concurrent chemotherapy
  Intervention: Drug: p53 with chemotherapy
• Experimental: p53 gene therapy alone
  Intra-tumor injectio of rAd-p53 gene with no concurrent treatment
  Intervention: Drug: p53 gene therapy

Inclusion Criteria:

1. Advanced stages of Oral and Maxillofacial malignant tumors (stage III and VI)
2. At least one target tumor can be injected with study drug, the largest diameter greater than 2 cm
3. Histologically confirmed Oral and Maxillofacial malignant tumors
4. No prior chemotherapy, radiotherapy or biological tumor therapy in 2 weeks
5. Age: 18-85 years old
6. Expected to survive more 12 weeks
7. ECOG:0-2
8. 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
9. Subject provided signed informed consent

Exclusion Criteria:

1. Hypersensitive to study drug
2. Tumor(s) locate very close to important blood vessels and nerves, which affect injection
3. With a coagulation and bleeding disorder
4. 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
5. Local infection close to injection site or systemic infection
6. Pregnant or lactating
7. Principle investigator consider not suitable -