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.

Study Overview

• Status: Unknown
• Conditions: Advanced Malignant Thyroid Tumors
• Intervention / Treatment: Drug: p53 gene therapy; Drug: rAd-p53 gene; Procedure: surgery; Radiation: p53 gene therapy with radioactive iodine

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.

• Study Type: Interventional
• Enrollment (Anticipated): 600
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610002
      • Recruiting
      • West China Hospital, Sichuan University
      • Contact: Jingqiang Zhu, PhD, MD; Phone Number: 86-28-81812477; Email: zjq-wkys@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall Response Rate	3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Progress-free survival	3 years

Collaborators and Investigators

• Sponsor: Shenzhen SiBiono GeneTech Co.,Ltd
• Investigators: Principal Investigator: Jingqiang Zhu, MD,PhD, Department Of Thyroid and breast Surgery, West China hospital, Sichuan University

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (ANTICIPATED): August 1, 2012
• Study Completion (ANTICIPATED): August 1, 2012

Study Registration Dates

• First Submitted: May 12, 2009
• First Submitted That Met QC Criteria: May 13, 2009
• First Posted (ESTIMATE): May 14, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): April 9, 2012
• Last Update Submitted That Met QC Criteria: April 6, 2012
• Last Verified: February 1, 2010

More Information

Terms related to this study

• Keywords: gene therapy; thyroid; p53 gene; malignant tumors
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Thyroid Diseases; Thyroid Neoplasms
• Other Study ID Numbers: rAd-p53-003