Phase 2 Study of REOLYSIN® in Combination With Paclitaxel and Carboplatin in Patients With Head and Neck Carcinoma

• Determine the objective response rate (complete response (CR) + partial response (PR)) of the treatment regimen in the study population [ Time Frame: For PR or CR, changes in tumor measurements must be confirmed 4 weeks after the criteria for response are first met. ] [ Designated as safety issue: No ]
  

• Evaluate the safety and tolerability of the treatment regimen in the study population. [ Time Frame: Within 30 days of last dose of REOLYSIN® ] [ Designated as safety issue: Yes ]
  
• Determine the disease control rate (CR, PR and stable disease (SD)), duration of response, time to disease progression and survival with the treatment regimen in the study population. [ Time Frame: For PR or CR, changes in tumor measurements must be confirmed 4 weeks after the criteria for response are first met. For SD, follow-up measurements must have met the SD criteria at least once after trial entry at a minimum interval of 12 weeks. ] [ Designated as safety issue: No ]
  

Biological: REOLYSIN®
3E10 TCID50, 1 hour intravenous infusion, administered on Days 1, 2, 3, 4 and 5 of a 21 day cycle
Drug: Carboplatin
5 AUC mg/mL min, 30 min intravenous infusion, given on Day 1 of a 21 day cycle
Drug: Paclitaxel
175 mg/m2, 3 hour intravenous infusion, given on Day 1 of a 21 day cycle

Squamous cell carcinoma of the head and neck is the sixth most common cancer in the world. More than 50% of patients diagnosed with advanced regional disease will relapse locally or at distant sites. Initial therapeutic options include irradiation, surgery and chemotherapy. The most commonly used agents are cisplatin and carboplatin, generally in combination with 5-FU or a taxane. Erbitux has recently been approved for use in first-line with radiation and in second-line as monotherapy. Only about a third of the patients will respond to first-line platinum-based therapy and the median overall survival is 6-9 months.

Preliminary assessment of a Phase 1 study being conducted in the UK investigating the combination of REOLYSIN®, carboplatin and paclitaxel suggested that patients with head and neck carcinomas may represent a group of patients in whom this treatment combination is active.

This Phase 2 study is designed to characterize the efficacy and safety of REOLYSIN® given intravenously in combination with paclitaxel and carboplatin every 3 weeks in patients with squamous cell carcinoma of the head and neck.

Response is a primary endpoint of this trial. Patients will be clinically evaluated after each course of treatment and radiologically every other cycle. A complete or partial response must be confirmed at least 4 weeks after the first assessment that documents such a response and every two cycles thereafter.

The safety of the paclitaxel, carboplatin and REOLYSIN® combination will be assessed by the evaluation of the type, frequency and severity of adverse events, changes in clinical laboratory tests, immunogenicity and physical examination.

Patients may continue to receive therapy under this protocol, provided they have not experienced either progressive disease or unacceptable drug-related toxicity that does not respond to either supportive care or dose reduction.