Principal investigator: Gordon H. Downie, MD, PhD
Co-investigators: Carter Childs MD and Jon Moran MD
This study is a pre-study on 20 patients who qualify, to determine the ability of video-assisted thoracoscopy or flexible bronchoscopy to deliver the PDT laser light via a micro-lens to the lining of the chest cavity or the airway.
Metastatic pleural malignancy (cancer between the chest wall and the surface of the lung) and cancer in the airways affects people's lives in many ways. Patients with cancer in the airway or chest cavity coming from the lung or another organ, have many symptoms that dramatically decrease their quality of life.
These symptoms can either result from the cancer in the airway, chest cavity space itself or from fluid produced by the cancer. These symptoms can include shortness of breath, chest pain or discomfort, cough and fever. The purpose of this study is to determine whether Photodynamic Therapy (PDT) to treat the cancer lesions can be delivered through a thoracoscope or bronchoscope.
Details
In order to qualify for this study, subjects must be well enough to undergo thoracoscopy or bronchoscopy. PDT is a therapy that works by using a drug (a photosensitizer called Photofrin), red light from a laser, and oxygen.
Each of these three things on their own is harmless but when combined in the right quantities it may be used in the treatment of cancer. When the photosensitizer is put into the body's blood stream it is taken up more in the tumor cells than in the normal surrounding cells.
This means that when the red light is shone onto the tumor there is more cell death in the tumor than in the surrounding cells. However, the drug does go a little bit into the entire body, particularly the skin. Therefore subjects will need to stay out of sunlight for at least 6 weeks after treatment, and limit sun exposure for up to 90 days. The photosensitizer is given 48 hours before the treatment is scheduled to begin.
Thoracoscopy is a surgical procedure, done under general anesthesia in the operating room. A cut is made on the side of the chest wall and a scope is inserted through that cut into the chest cavity. After inspection of chest cavity space, the amount of disease will be determined. After determination of extent of disease, PDT will be given.
Bronchoscopy is a non-surgical procedure done under light sedation usually as an outpatient; the scope enters the airway from the nose and throat. The scope will allow inspection of the airway and after determination of extent of disease PDT will be given.
Subjects in this study will receive the Photofrin short intravenous infusion. Two days later they will undergo thoracoscopy or bronchoscopy as well as PDT. The amount of PDT depends on the cancerous lesion in the chest cavity or airway. Two to three days later they will undergo a follow up thoracoscopy or bronchoscopy to determine response to the treatment.
Plan and procedures
It will be necessary to determine the extent of research subjects' disease before and after receiving treatment. This will be done in the following manner: An investigating physician will perform an examination.
Subjects may have certain breathing tests performed. The usual tests will be a pulmonary function test, which measures both the ability of the airway to move air, and the relative size of the lungs. This is done at the hospital and. consists of blowing into a machine, which makes recordings of the patient's performance. The patient will have chest x-rays and also a special type of x-ray called a CAT scan performed on the chest. This test is a standard test for the evaluation of the subject's response to therapy.
Patients will come to the hospital or the physician's office to receive a Photofrin infusion. This should take about 10-20 minutes after which the patient can return home, however the skin will be very sensitive to sunlight for up to 90 days following this infusion.
Sunlight sensitivity could cause serious skin bums, even causing death, if direct exposure to sunlight is not avoided. After the injection of Photofrin, the skin and eyes will become photosensitive (sensitive to light). Photosensitivity reactions may occur in minutes, so immediately after receiving the Photofrin injection and for the first 30 days after the injection, there are certain precautions that research subjects must take in order to avoid a serious bum (sunburn, redness, and swelling).
These precautions include avoiding bright lights and direct sunlight. However, if the skin is exposed to direct sunlight, subjects will get severe sunburn, possibly requiring hospitalization. In order to avoid sunburn, subjects will be instructed to wait until sundown to go outside. If they must go outside during daylight hours, they must cover as much of my skin as possible by:
Wearing a wide-brimmed hat to protect the face
Wearing a long sleeved shirt to protect the arms
Wearing gloves to protect the hands
Wearing slacks to protect the legs
Wearing socks to protect the ankles
Wearing shoes to protect the feet
Carrying an umbrella if the sun is shining
Keeping drapes or blinds closed over windows
Clothing should be dark covered, tightly woven fabric, if possible. Patients should take these precautions even on cloudy days and while in a car. It is extremely important to wear gloves while driving to protect the hands. Patients should also wear dark sunglasses to protect the eyes from the light.
Also, for 90 days after the injection, patients should avoid bright examination lights like those in a dentist's office, operating room lights, light bulbs without a shade that are only a few inches away, and helmet-type hair dryers like those found in beauty salons. Hand-held hair dryers on a low setting are safe to use. Watching television, movie theaters and normal indoor lights are allowed.
Sunscreen will not protect the skin, no matter how high the SPF. Sunscreens protect against non-visible, not visible light to prevent sunburns. Photofrin is activated by visible light, and therefore will cause bums despite sunscreens.
After the first 15-21 days, patients may do a test for photosensitivity by exposing a small area of skin - on the back of the hand - to sunlight. One way to do this is to cut a small hole (about 2 inches) in a paper bag that they can put the hand into. The patient can expose the unprotected skin to sunlight for 10 minutes. If redness, swelling, or blistering occurs within 24 hours of the exposure, the patient will need to continue taking the precautions for another two weeks. If no reaction occurs within 24 hours of exposure, the patient may gradually increase his outings into
sunlight. If patients have any questions about this self-test or confusion they should do not perform the test, call the study doctor or nurse to perform the test.
Photofrin can remains in the skin for up to 90 days following injection. For that reason, the patient should continue to watch for any reaction, and limit the amount of time the skin is exposed to sunlight 90 days following injection. The patient should NOT use his face to do the test for photosensitivity.
A reaction will look like sunburn. The skin will appear red and swollen. Just as with a sunburn, blisters may form. If a patient sees what appears to be sunburn, he should call his doctor at once to get information on how to treat it.
Hospitalized patients can receive the infusion during their stay.
Two days after the receiving the drug, patients will have thoracoscopy or bronchoscopy performed. A thoracoscopy consists of being taken to a procedure or operating room in the hospital. The patient will be given general anesthesia or light sedation to alleviate any pain and discomfort associated with the procedure. Under sterile conditions, small cuts will be made on my chest wall and thoracoscopy will be performed through those cuts. A thoracoscope is a lighted tube with a camera that will be used to visualize the chest cavity space during thoracoscopy. Biopsies of
the chest cavity lesions will be taken, if needed. After examination of the chest cavity space, the physician and surgeon will determine the extent of disease. A chest tube will be placed in my chest cavity to drain fluid. Any pain or discomfort following the procedure will be treated with pain medication given by mouth or into the blood directly. The patient will remain hospitalized for up to 12 days after the initial thoracoscopy.
A bronchoscopy consists of being taken to a procedure room in the hospital. Medications will be given through an IV tube into the blood that will achieve light sedation and discomfort control; the patient will not be made completely asleep. A bronchoscope is a small, flexible tube with a light and a camera lens on one end. It will be inserted through the patient's nose or mouth and guided into his airways.
The physician will asses the extent of disease in the airways, and may take photographs or biopsies if needed. After completion of the procedure, the bronchoscope is removed and the patient will be allowed to recover from the sedation. If the patient is an outpatient, he can expect to be allowed to go home within two hours of the completion of the bronchoscopy.
PDT causes damage to cancer cells within the first 48 hours and during this period the patient will remain in the hospital. Treatment outcomes will be assessed by daily physician visit, observing development of new symptoms and/or changes in existing symptoms, physical examination, pulse oximetry, serial complete blood count and changes in chest tube drainage.
After the initial thoracoscopy, or bronchoscopy, patients will return for follow up thoracoscopy or bronchoscopy. Again the amount of disease will be determined and response to the PDT to the single treated lesion will be evaluated by biopsy and photography. After thoracoscopy the patient will again have a chest tube drain in his chest cavity and will remain in the hospital for up to 10 days.
Potential risks and discomforts
All medical therapies carry some risk. The following may occur and the investigators will try to minimize the likelihood of their occurrence: Exposure to sunlight and bright lights will cause a sunburn-like reaction on the skin. In order to prevent this patients will need to avoid direct sunlight for approximately 12 weeks after the injection. If patients do go outside they must have clothing covering all exposed areas (head, hands feet etc). Photodynamic therapy, which includes the salvage procedure (removal of dead tissue), can also cause some small amount of bleeding in the chest cavity, which should resolve on its own. However, in very rare occasions it can cause life-threatening bleeding which may require surgery to correct.
Thoracoscopy carries the risk associated with general anesthesia. This may require additional medications administered and assisted ventilation by means of a ventilator. Further, thoracoscopy itself carries the risks of lung collapse and bleeding into the space around the lung, infection, and prolonged stay on the ventilator. The physician will explain this to the patient and the patient will be asked to sign a consent form for that procedure.
Bronchoscopy carries the risk associated with light sedation. This may require additional medications to be administered or assisted ventilation by means of a ventilator. Further, bronchoscopy carries the risks of coughing and sore throat, which .can be relieved by simple pain medications. It also carries the risk of airway tearing, which can lead to lung collapse requiring insertion of a chest tube for relief, or major bleeding which may require surgery to correct.
Unanticipated side effects may occur which have not been reported. If patients have any unusual symptoms, they will report them immediately to the nurse and physician. In an attempt to avoid side effects, the physician will examine the patient and obtain laboratory tests (blood tests, chest x-rays, scans, etc.) to determine the effects of the treatment.
If the patient develops side effects, a decision whether to continue the treatment or modify the treatment will be made. Modification may include stopping the further photodynamic therapy, radiation therapy or chemotherapy.
In an attempt to avoid side effects, the physician will examine the patient and obtain appropriate laboratory tests (blood tests, x-rays, CT scans, etc.) to determine the effects of the treatment and alter the drug doses if necessary.
Potential benefits
There may or may not be a direct medical benefit to the research subject. The information learned from this study may benefit other patients with lung cancer. Potential benefits from this study may include improvement in the research subject's breathing with less difficulty or discomfort.
Alternative courses of treatment
Standard treatment for this disease is chemotherapy with or without radiation, or occasionally surgery with or without radiation following surgery. The surgical treatment is a thoracoscopy for the purpose of pleurodesis (causes the lung to stick to the chest wall).
