P53 Gene Combined With Radio- and Chemo-therapy in Treatment of Unresectable Locally Advanced Head and Neck Cancer

Study Overview
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Brief Summary
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The objectives of this study are to investigate the efficacy and safety of rAd-p53 gene combined with radio- and chemo-therapy vs. radio- and chemo- therapy only in treatment of unresectable, locally advanced head and neck cancer. This is a phase 2, open labeled, and active-controlled study.

Detailed Description
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To evaluate benefits of rAd-p53) gene therapy combined with radio- and chemo-therapy in treatment of unresectable, locally advanced head and neck cancer, total of 60 patients with above condition will be randomly assigned to two groups: the experiment group (EG) and the control group (CG). The EG received multi-point injections of rAd-p53 into tumor on day 1, 8 and 15 at a dose of 2 × 10^12 viral particles (VP) in a 21-days cycle. Both EG and CG were given radiotherapy at a total dose of 60 Gy and chemotherapy (Cisplatin 100 mg/m2 IV on days 1 plus paclitaxel 30 mg/m2 IV on day 1, 8 and 15). The patients will be treated until disease progression, withdrawal from study, or untolerated adverse events. study endpoints are efficacy (Progression-free survival, overall survival) and safety variables.

Official Title
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Recombinant Adenoviral Human p53 Gene Combined With Radio- and Chemo-therapy in Treatment of Unresectable, Locally Advanced Head and Neck Cancer - a Open-labeled Randomized Phase 2 Study

Conditions
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Advanced Head and Neck Cancer

Intervention / Treatment
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* Drug: rAd-p53
* Radiation: radiation
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histopathologically diagnosed head and neck cancer; unresectable, locally advanced; 18 years or older; with an Eastern Cooperative Oncology Group (ECOG) score of 0-2; with normal tests of hemogram, blood coagulation, liver and kidney function; 6.signed the informed consent form. Exclusion Criteria: Serious blood coagulation disorder, bleeding tendency, platelet < 6 * 1000000000/L; have serious heart, lung function abnormalities or severe diabetes patients; active infection; severe atherosclerosis; AIDS patients; serious thrombotic or embolic events within 6 months; renal insufficiency requiring hemodialysis or peritoneal dialysis; pregnant or lactating women; mental disorder or disease.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rAd-p53 plus radiation and chemotherapy<br>rAd-p53 tumor injection combined with radio- and chemo-therapy. | Drug: rAd-p53<br>* multi-point injections of rAd-p53 into tumor on day 1, 8 and 15 at a dose of 2 × 10^12 viral particles (VP) in a 21-days cycle.<br>* Other names: p53 gene therapy;Radiation: radiation<br>* radiation therapy will be given at a total dose of 60 Gy by 2.0 Gy/fraction, daily Monday-Friday for 6 weeks.<br>Drug: Cisplatin<br>* Cisplatin 100 mg/m2 IV on days 1 plus paclitaxel 30 mg/m2 IV on day 1, 8 and 15<br>* Other names: chemotherapy: cisplatin;|
| Active Comparator: radiation and chemotherapy<br>radiation combined with chemotherapy | Radiation: radiation<br>* radiation therapy will be given at a total dose of 60 Gy by 2.0 Gy/fraction, daily Monday-Friday for 6 weeks.<br>Drug: Cisplatin<br>* Cisplatin 100 mg/m2 IV on days 1 plus paclitaxel 30 mg/m2 IV on day 1, 8 and 15<br>* Other names: chemotherapy: cisplatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival | Patients will be followed up until progression or death, withdrawal from study, or until data cut-off after 3 years. | three years after starting treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Adverse events | from starting study treatment until 30 days after the last study treatment | 
| overall survival | Patients will be followed up until death, withdrawal from study, or until data cut-off after 3 years. | three years after starting study treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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p53, gene therapy, head and neck cancer