A phase 2 trial of surgery with perioperative INGN 201 (Ad5CMV-p53) gene therapy followed by chemoradiotherapy for advanced, resectable squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx: Report of the southwest oncology group

Objective: To assess the feasibility of treating patients with high-risk stage III and IV squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx with perioperative adenovirus-p53 (INGN 201) gene therapy along with surgery and chemoradiotherapy. Design and Setting: A phase 2 study in a multi-institutional setting within the Southwest Oncology Group. Patients: Thirteen individuals who met the following entry criteria: newly diagnosed, previously untreated squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx; selected stage III or IV disease without distant metastases; and surgically resectable disease. Interventions: Surgery, perioperative INGN 201 gene therapy, and postoperative chemoradiotherapy. Main Outcome Measures: Overall patient status, tumor status, adverse effects, accrual rate, and percentage of patients successfully receiving the required doses of INGN 201. Results: All 13 patients received surgery and perioperative INGN 201 injections in the primary tumor bed and the ipsilateral neck. In addition, 3 patients received injections in the contralateral neck. Three patients did not receive chemoradiotherapy. One patient had a grade 2 fistula of the oral cavity. Of the 10 patients with evaluable data, 2 experienced grade 4 adverse events, 1 owing to hypokalemia, hyponatremia, vomiting, leukopenia, and neutropenia and 1 owing to increased aspartate aminotransferase and alanine aminotransferase levels. Seven other patients experienced grade 3 adverse events. The estimate of 1-year progression-free survival is 92%. Conclusions: This trial demonstrated the feasibility of handling and delivering a very complex gene vector safely in multiple cooperative group institutions without significant incident. Intraoperative INGN 201 gene therapy is technically feasible, but it has many logistical problems when performed in a multi-institutional setting. Regulatory requirements might have hindered accrual in this multi-institutional setting. Disease control seems to be promising; however, no definitive conclusion can be made with this small sample size. Trial Registration: clinicaltrials.gov Identifier: NCT00017173.