Study Doctor: Dr. Rosa Cuenca
Sponsor: Light Sciences Corporation ("LSC")

This research study is designed to evaluate the safety and efficacy of an investigational drug called LS11 and an investigational device (LumaflexTM) that emits light.

The Lumaflex M device is referred to as a "light bar." Together the investigational drug and light bar are called the Lit/M System and the therapy is known as Light Infusion TechnologyTM, LSC's brand of photodynamic therapy. The goal of photodynamic therapy is to localize the "treatment effect" to just the target tumor which may minimize the side effects of the treatment. Neither part of the Lit/M System has been approved for marketing by the U.S. Food and Drug Administration (FDA). The Litx TM system is to be tested in patients with liver metastases from colorectal cancer that have failed previous chemotherapy.

Previous clinical studies were conducted by injecting LS11 into the veins of 96 patients with skin cancer, lung cancer, or cancers that were accessible to percutaneous light bar implantation. LS11 administered by itself has little or no activity; however, once the drug is exposed to light of a specific wavelength, it becomes activated, which may, in turn, cause the destruction of tumor tissue.

The present study is designed to study the safety and efficacy of the LitxTM system by delivering the light from the light bar (or bars) which will be implanted directly through the skin and into the metastasized liver lesions.

Information about the Lit/M system
LS11 has been used in prior investigational studies administered by injection into a vein. LS11 is a "light sensitive" drug which means that after administration LS11 can be activated by light from a light bar placed inside the tumor. In this study, the same dose of LS11 that was used previously will be administered intravenously. The light bars are small and flexible, and they will act as a light source to activate LS11. The light bar is connected to a power controller that will be used to deliver light for a period of about 2 hours and 45 minutes.

Description of the research study and procedures to be followed
Approximately 25 patients will participate in this research study at approximately 6 sites throughout the United States and Europe. A CT will be performed on the patients' tumor(s) during medical review by the study doctor to ensure that the size, shape and the location of the patients' tumor(s) are appropriate for the insertion of the light bar(s).

The study doctor will give the patients local anesthesia at the light source entry site. Then a 0.5 cm superficial incision will be done in the skin and the light source will be inserted. The size of the light source will be either 1.5 mm or 3 mm in diameter, and 10 mm or 25 mm in length, depending of the size of the tumor. No more than four light sources will be used at any single treatment.

The light sources may be used in a single lesion or in multiple lesions. On the day of the treatment, one or more of the light bars will be placed in the patients' tumor(s). A CT or an ultrasound may be used to monitor the placement of the light bar(s). Patients will then receive an intravenous injection of LS11.

One hour following the LS11 administration, the light bar(s) will begin to emit light. The light delivery period will be about 2 hours and 45 minutes. Patients will need to stay overnight at PCMH for observation. All these procedures are experimental. Additional tests (vital signs, cancer related symptoms, blood tests, and CT) will be carried out periodically throughout the research subject's participation in the study.

The study doctor may recommend that patients receive a standard chemotherapy 30 days after the Lit/M treatment. If patients agree to receive the chemotherapy as recommended, they will be asked to come back for another follow-up visit 30 days after receiving the chemotherapy. Vital signs, cancer-related symptoms, blood tests and CT would again be carried out during this visit.

If patients do not receive chemotherapy at the day 30 follow-up visit after the Lit/M treatment, they will also be asked to come back for another follow-up visit 60 days after the LitxTM treatment. Their participation in this study is expected to be approximately 60 days with or without the day 30 chemotherapy.

Risks and discomforts
All drugs have the potential to cause some side effects or other reactions. Since the study medication is experimental, when taken alone or in combination with other medications, there may be other risks that are unknown. All drugs have a potential risk of an allergic reaction, which if not treated promptly, could become life-threatening. However, all reasonable precautions will be taken to reduce these risks during the study.

Risks Associated with LS11
Although every effort will be made to ensure that during injection LS11 will not spill over from the vein to the surrounding tissue, there is a possibility of such incidence. The injection site must be protected from light for as long as needed to avoid any sun-burn like symptoms. The study doctor will determine the appropriate length of time for skin protection.

Because LS11 is light sensitive, it may cause burns to the patients' skin at the injection site or eyes. Appropriate precautions for protection from strong room light and sunlight will begin immediately after drug administration and continue for at least three days, unless the patients are otherwise instructed by the study doctor.

Study participants will be asked to wear protective clothing on the entire body. Commercial sunscreens are not effective at protecting patients from the external light when LS11 is in their blood. They will be instructed on how to protect themselves from external light exposure during the entire study period.

Due to the nature of its sensitivity to light, once injected with LS11, patients should not undergo any surgical operation that may use strong lights during the treatment. In the event of emergency surgical procedures, adequate procedures should be undertaken to minimize exposure of the skin and other exposed tissues to operating room lighting.

Patients should protect the skin from direct sunlight or very bright indoor lighting (e.g. fluorescent lighting or tungsten discharge lamps) for 2 weeks after LS11 administration. Exposure to sunlight should be increased gradually and cautiously according to the study doctor's instructions. When outside, patients should wear hats, long-sleeve shirts, long pants or long skirt, gloves, socks, and sunglasses.

Patients should avoid any dental or eye examination for one month after the procedure to protect themselves from the strong light used during these kinds of examinations.

The most common side effects after taking LS11 reported in other studies include itching, pain and burning, face edema/swelling, hot flush, redness of the skin, blistering, diarrhea, difficulty swallowing, nausea/vomiting, constipation, heart burn, coughing, phlegm, shortness of breath, sore throat, nasal obstruction, fever, feeling "out-of-sorts", pain, headache, toothache, earache, hoarse voice, insomnia, chest discomfort, stiffness.

The most common changes in laboratory assessment of the blood attributed to LS 11 reported in other studies include both increases and decreases in the number of white blood cells, decreased red blood cells, decreased hemoglobin, an increase or decrease in the number of platelets in your blood that help with clotting, an increase in creatinine, and an increase in blood urea. The following changes were noted in the urine: changes in color (green), urinary sugar, increased urinary protein, and blood in the urine.

Patients are advised not to use a pulse oximeter (a device that measures the amount of oxygen in the blood) during the treatment for it may cause severe burn to the skin surface in contact with the pulse oximeter device.

Risks associated with the light bars
Potential complications of insertion of the light bars are bleeding at the site of implantation, breakage of the light source while it is implanted, sepsis (infection of the blood or tissues), unwanted movement of the light bars, exit site infection, fistula (an abnormal passage or tunnel from one surface to another), collapse or bleeding of the lungs, hematoma (bruise), cuts or tears of blood vessels or internal organs, fever, low blood pressure, intolerance reaction to the implanted light bar, or photodynamic injury of normal tissues (damage to normal vessels or organs near the light bar).

Reproductive risks
There may be risks to an embryo, fetus, or nursing infant and effects on semen are currently unknown. If a patient suspects that she may be pregnant or if the patient is a male and suspects his partner may be pregnant during the trial, they should contact the study doctor immediately.

Risks of a blood draw
When blood is drawn for study-related testing, patients may experience some pain, bruising, dizziness, or (rarely) infection from drawing the blood. Approximately 5 teaspoons of blood will be drawn at each blood draw.

Risks of CT
CT scanning uses x-rays to create images of tissue below the skin. X-rays are known to be carcinogenic (producing cancer cells) but the risk of cancer from x-rays is very slight. The amount of x-ray exposure that most people receive in a lifetime is not known to produce any illness. The amount of x-ray exposure involved in this study will be the same as for subjects with the participant's disease who do not participate in this study.

Risks of MRI
MRI scanning uses a strong magnet and radiowaves to make images of the body interior. The scanning procedure is very much like an x-ray CT scan. Patients will be asked to lie on a long narrow couch for a certain amount of time while the machine gathers data.

If patients have any history of head or eye injury involving metal fragments, if they have ever worked in a metal shop, if you have some type of implanted electrical device (such as a cardiac pacemaker), if they are wearing metal braces on their teeth, or [for women] if they could be pregnant, they should not have an MRI scan.

Allergies to CT contrast agents
Certain patients are at higher risk for experiencing a reaction to the CT contrast agents. Patients may be at higher risk for adverse effects of contrast if they have already had a moderate or severe "allergic-like" reaction to contrast material which required treatment; have severe allergies or asthma; have severe or incapacitating heart disease; have multiple myeloma, sickle cell disease, polycythemia, or pheochromocytoma; have severe kidney disease, particularly caused by diabetes;
are diabetic and taking Glucophage (methformin HCI) oral hypoglycemic.

Significant new findings
Study participants will be told promptly if new information becomes available that may affect their willingness to continue participating in this study. If new information becomes available, they may be asked to sign a replacement consent form with the new information added.