A Study of REOLYSIN® in Combination With Paclitaxel and Carboplatin in Patients With Squamous Cell Carcinoma of the Lung

A Phase 2 Study of Intravenous Administration of REOLYSIN® (Reovirus Type 3 Dearing) in Combination With Paclitaxel and Carboplatin in Patients With Squamous Cell Carcinoma of the Lung

The purpose of this Phase 2 study is to investigate whether intravenous administration of REOLYSIN therapeutic reovirus in combination with paclitaxel and carboplatin is effective and safe in the treatment of squamous cell carinoma of the lung.

Lung cancer remains the most common cancer and cause of cancer-related mortality in the United States. In 2008, there was an estimated 215,000 new cases of lung cancer diagnosed and roughly 162,000 deaths from lung cancer (NCI 2009). The majority (85%) of patients with a diagnosis of lung cancer will have non-small cell lung cancer (NSCLC).

The combination of paclitaxel and carboplatin has become the most commonly prescribed chemotherapy regimen for the treatment of advanced NSCLC in the United States. Laboratory studies of combinations of REOLYSIN with a variety of chemotherapeutic agents has shown that the combination of REOLYSIN and paclitaxel was invariably synergistic, even in cells with drug resistance or limited sensitivity to the reovirus. Moreover, reovirus activity was dramatically increased in the presence of the taxane.

The 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 carinoma of the lung.

Response is a primary endpoint of this trial.

The safety of the treatment 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 chemotherapy combined with REOLYSIN for up to 8 cycles and may continue indefinitely on REOLYSIN monotherapy 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.

Inclusion Criteria:

• have histologically or cytologically confirmed metastatic stage IIIB (pleural effusion; IVA on revised IASLC staging) or stage IV, or recurrent squamous cell carcinoma of the lung.
• have measurable disease.
• be chemotherapy naïve for their metastatic or recurrent SCCLC, with some exceptions.
• have NO continuing acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedures.
• have an ECOG Performance Score of ≤ 2.
• have a life expectancy of at least 3 months.
• absolute neutrophil count (ANC) ≥ 1.5 x 10^9; Platelets ≥ 100 x10^9 (without platelet transfusion);Hemoglobin ≥ 9.0 g/dL (with or without RBC transfusion); Serum creatinine ≤ 1.5 x upper limit of normal (ULN); Bilirubin ≤ 1.5 x ULN; AST/ALT ≤ 2.5 x ULN.
• negative pregnancy test for females with childbearing potential.

Exclusion Criteria:

• receive concurrent therapy with any other investigational anticancer agent while on study.
• have a known past or current history of brain metastasis(es).
• be on immunosuppressive therapy or have known HIV infection or active hepatitis B or C.
• be a pregnant or breast-feeding woman.
• have clinically significant cardiac disease.
• have dementia or altered mental status that would prohibit informed consent.
• have any other acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the Principal Investigator, would make the patient inappropriate for this study.