rAd-p53 Gene Therapy for Advanced Malignant Thyroid Tumors

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

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.

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.

Inclusion Criteria:

1. Advanced stages of thyroid 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