Phase 3 Trial of Litx™ Plus Chemotherapy vs. Chemotherapy Only Treating Colorectal Cancer Patients With Recurrent Liver Metastases

A Multicenter Multinational Phase 3 Randomized Study to Evaluate the Safety and Efficacy of Treating Colorectal Cancer Patients With Recurrent Liver Metastases Using the Litx™ System Plus Chemotherapy as Compared to Chemotherapy Only

The purpose of the study is to assess the overall survival and progression free survival of patients treated with Litx™ + chemotherapy versus chemotherapy alone in the treatment of Colorectal Cancer with recurrent liver metastases, and to demonstrate the safety of Litx™ therapy.

Litx™ consists of a light-activated drug, talaporfin sodium (LS11, Light Sciences Oncology, Bellevue, Washington), and a light generating device, composed of light-emitting diodes (LEDs), that is energized by a power controller and percutaneously placed in the target tumor tissue inside the body.

Randomized, stratified, two arm study:

• Litx™ and chemotherapy arm (FOLFOX4 or FOLFIRI)
• Chemotherapy only arm (FOLFOX4 or FOLFIRI)

For patients who have progressed on FOLFIRI, they will be treated with Litx™ plus FOLFOX4 versus FOLFOX4 alone; and for patients who have progressed on FOLFOX, they will be treated with Litx™ plus FOLFIRI versus FOLFIRI alone.

Stratification upon enrollment by chemotherapy and tumor sum of the longest diameter (SLD) (SLD < 4 cm or SLD ≥4 cm but ≤7.5 cm).

Inclusion Criteria:

• Patients with recurrent metastatic liver lesions from colorectal cancer who progressed on either FOLFOX or FOLFIRI
• Biopsy proven evidence of colorectal cancer
• At least one liver lesion that can be measured in one dimension at >10 mm with spiral CT scan (CT preferred but MRI allowed)
• ECOG Performance Status 0-2
• Life expectancy of at least 16 weeks
• At least 30 days must have elapsed since the completion of any prior antineoplastic therapy and the patient must have recovered from acute side effects before day 0
• Understanding and ability to sign written informed consent
• 18 years of age or more
• Adequate hematologic, liver and renal functions as evidenced by the following: WBC > 2.5 × 10^9/L ; Platelet Count > 100 × 10^9/L ; Hemoglobin > 90 g/L ; Neutrophils >1.5 × 10^9/L ; PT and PTT < 1.5 Control ; SGOT, SGPT < 5 × ULN ; GGT < 5 × ULN ; Alkaline phosphatase < 5 × ULN ; Bilirubin < 3 × ULN ; Creatinine < 1.5 × ULN

Exclusion Criteria:

• Patients who are candidates for complete surgical resection
• Patients who received bevacizumab (Avastin®) or cetuximab (Erbitux®) within 30 days of randomization. Use of bevacizumab or cetuximab is prohibited while participating in this study
• Patients who would require more than a total number of 12 light source applications over three Litx™ experimental treatments (no more than 4 light sources per treatment).
• Patients who have a single measurable tumor greater than 7.5 cm in any organ
• Target lesions irradiated within 3 months of randomization
• Patients with tumor involvement in greater than 50% of parenchyma of the liver
• Evidence of major vessel invasion of any organ
• Patients with any non-colorectal cancers except for adequately treated basal or squamous cell skin cancer, or adequately treated stage I or II cancer from which the patient has been disease-free for ≥ 3 years, or other cancer from which the patient has been disease-free for ≥ 5 years
• Known sensitivity to porphyrin-type drugs or known history of porphyria
• Pregnancy or breast-feeding patients. A negative pregnancy test (urine or serum) from women of childbearing age is required prior to enrollment. A fertile patient must use effective contraception during participation in the study
• Concurrent participation in another clinical trial involving experimental treatment
• Any concurrent disease or condition that in the opinion of the investigator impairs the patient's ability to complete the trial such as psychological, familial, sociological, geographical or medical conditions which in the Principal Investigator's opinion could compromise compliance with the objectives and procedures of this protocol or obscure interpretation of the trial's data.