Photodynamic Therapy for Pre-Malignant Head and Neck Tumors
Consent Form
University of Pennsylvania Health System
Principal Investigator: Harry Quon, MD (215) 614-0392
(24 hour 215-662-6059 – ask for the Radiation Oncologist on call)
Principal Investigator: Ara Chalian, MD (215) 349-5559
(24 hour 215-662-4000 – ask the Otolaryngologist on call)
Sub - Investigators: Robert Lustig, MD (215) 349-8429
(24 hour 215-662-6059 – ask for the Radiation Oncologist on call)
Stephen Hahn, MD (215)662-7296
(24 hour (215)662-6059 – ask for the Radiation Oncologist on call)
Gregory Weinstein, MD (215) 349-5390
(24 hour 215-662-4000 – ask for the Otolaryngologist on call)
Bert W. O’Malley, Jr., MD (215)349-5383
(24 hour 215-662-4000 – ask the Otolaryngologist on call)
Introduction
This is a clinical trial (a type of research study). Clinical trials include only patients who choose to
take part. Please take your time to decide if you want to join this study. Discuss it with your friends
and family. Before you make your decision, you should know and understand the treatment proposed
in this study, how it will be given, how the treatment may help you and how the treatment may harm
you. You have the right to know about the procedures used in this research study and the risks,
benefits and alternatives to the treatment in this study. If you choose to participate in this study, you
will be given a copy of this consent form to keep. You are being asked to participate in this study
because you have a precancerous lesion of the head and neck.
Why is this study being done?
Doctors at the University of Pennsylvania Medical Center are researching better ways of treating
premalignant (pre-cancerous) and in-situ (noninvasive) head and neck cancer. These lesions are
usually very superficial (do not invade deeply) and can be removed with surgery. However, even after
complete surgical removal, they often return or a new lesion may develop in a different area.
The purpose of this study is to test a new, investigational type of treatment, photodynamic therapy
(PDT) using a photosensitizing agent, 5-aminolevulinic acid (Levulan®). Photodynamic therapy is a
treatment in which a light-sensitive drug is given. It concentrates in the area where cancer cells or
precancerous cells are located. The drug is activated by laser light, which then kills your cancer cells
and precancerous cells. Researchers want to study the effects of PDT on your precancerous lesion and
find out if it will prevent it from coming back (recurring).
This is a Phase I study which means that the goal of this study if to find the safest and most tolerable
dose of laser light that may be used on premalignant and in-situ head and neck cancer. Therefore, you
may not receive exactly the same dose as other patients enrolled in the study. This study is a dose
escalation study in which the first several patients will receive a low dose of laser light given in one
treatment period. After these patients get PDT, they will be observed for side effects. If no significant
side effects are seen, the next group of patients will receive the same dose of light, but it will be
divided into 2 treatment sessions separated by a 2.5 minute break. If no significant side effects are
seen, the next group of patients will receive a slightly higher dose of light. Again, if no significant side
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effects are seen, the next group will receive the same light dose given in 2 treatment sessions.
Although all patients will receive the same dose of drug, the light dose will be increased step by step.
This study will evaluate different doses of the light treatment to see if they are effective in eliminating
precancerous lesions and in situ cancerous lesions of the head and neck. The study will also evaluate
the side effects of the drug, Levulan®, as well as the side effects of the laser light treatment. This
study will also compare the effects, both good and bad, of continuous light treatment with treatment
where the light is given in 2 sessions.
How many people will take part in the study?
About 24 patients will take part in this study at Virginia Mason Medical Center and the University of
Pennsylvania combined.
What is involved in the study?
If you agree to be evaluated for this research study, you will have certain tests and procedures (called
screening) to determine that you are not at increased risk for side effects and are eligible to receive
PDT with Levulan®. You must sign this consent form before having any of these screening tests.
Your doctor will record your medical history and perform a physical examination. About 3 tablespoons
of blood will be drawn from your vein for laboratory testing. If you are a female capable of bearing
children, you will undergo a blood test to see if you are pregnant. You will undergo
nasopharyngolaryngoscopy (a flexible scope is placed through your nose to examine your nose and
throat). If you have already had a biopsy of the abnormal areas, this tissue will be examined under the
microscope at the University of Pennsylvania Medical Center before you may be treated in the study.
If you have not already had a biopsy performed, you will undergo this before study entry to be sure the
areas of abnormality are either premalignant or noninvasive cancer.
Prior to the light exposure, you may be given medication into your veins to prevent pain and relax you,
or you may be given general anesthesia (you are given drugs to make you unconscious), depending on
what your doctor feels is best for you. You will also be given anti-nausea drugs. At the time of
treatment, you will be given by mouth a dose of Levulan® mixed in water. For the next 4-6 hours, you
will need to be in a dimmed light environment. You should not be exposed to any direct sunlight. If
you go outside, you will need to wear long sleeves, long pants, socks, a hat, gloves and sunglasses.
You will undergo PDT in the operating room at the University of Pennsylvania Medical Center. The
doctors will decide whether you will receive conscious sedation or general anesthesia. The doctors will
apply the laser light to your precancerous lesion or tumor. During the light exposure, you will wear
special goggles to protect your eyes and your skin will be covered to prevent activation of any drug
that has accumulated there. You will be in the operating room for approximately one hour. After the
procedure, you will go to the recovery room for observation. Your doctors may let you go home later
that day, or they may admit you overnight to the hospital for additional observation. This decision will
be based upon your condition and how your body responds to the treatment.
Once your treatment is complete, you will need to remain in a dimmed light environment for 48 hours.
During this time, you should avoid direct sunlight as mentioned above, but indoors, all lights should be
dimmed. You need to avoid direct sunlight and bright lights because Levulan® makes your skin
sensitive to light, and exposure to direct sunlight and bright lights can cause burning, itching and
swelling of the skin.
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Following treatment, on the first day after, 3-5 days after, 13-15 days after, 1 month after, and every 3
months for the first 2 years after treatment, you will be asked to come in to see the doctor to have the
treatment area checked and to see if you have had any side effects from the treatment. At each of these
visits, you will also have some blood tests. About 3 tablespoons of blood will be drawn to measure
your blood counts, the minerals in your blood, your liver function, and your kidney function.
Depending on the location of the treated area, you may also undergo nasopharyngolaryngoscopy at
your 1 month follow-up appointment. After this, you will be asked to come in to see the doctor once a
year to have your treatment area checked. Your doctor will decide if you should have any other testing
(blood tests or x-ray tests) at that time.
The table below outlines when each follow-up visit will occur and what will take place at each visit.
Screening/
Eligibility
Day
0
Day
1
Day
3-5
Day
13-15
Day 30
Physical Examination
CBC
Chemistry*
PT, PTT
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
CXR
Nasopharyngolaryngoscopy
Tissue Biopsy or
Pathology Review
Levulan® Administration**
PDT***
Evaluation of Treatment
Area and Symptoms
+
+
Every 3
Months
For 24
Months
+
+
+
Annually
+
○
+
+
+
+
+
+
+
+
+
How long will you be in the study?
Follow up visits with your doctor will be scheduled for one day after, 3-5 days after, 13-15 days after,
one month after your treatment, then every three months for two years, and then annually for the rest of
your life.
The researcher may decide to take you off this study if it is in your medical best interest, your
condition worsens, or if new information becomes available and this information suggests the
treatment will be ineffective or unsafe for you.
You may decide to stop participating at any time. However, if you do decide to withdraw from the
study, we encourage you to talk to the researcher and your regular doctor first.
If your tumor or precancerous lesion comes back or grows larger 3 months or longer after you have
PDT, you may undergo PDT a second time. In order to be treated a second time, you will undergo all
the screening tests again as described above.
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What are the risks of the study?
While on the study, you are at risk for these side effects. You should discuss these with the researcher
and/or your regular doctor. There also may be other side effects that we cannot predict. Drugs may be
given to make side effects less serious and uncomfortable. Many side effects go away shortly after
treatment, but in some cases side effects can be serious or long lasting or permanent.
What are the risks of blood drawing?
The risks of blood drawing include pain (common), bruising or bleeding (occasionally), and infection,
possible fainting, and, nerve damage (rarely).
What are the risks of nasopharyngolarnygoscopy?
Your doctor will apply a numbing medication inside your nostrils so you should not feel any pain from
the tube in your nose. Some people find the tube is uncomfortable, however. The numbing medicine
wears off in an hour, and you should not eat or drink anything until it has worn off.
What risks are associated with Photodynamic Therapy?
Likely but Temporary (occurring in 80 – 100% of all patients)
Skin sensitivity to light (can include severe burning of the skin including itching and swelling)
Pain in area of treatment both during and after treatment
Less Likely but Temporary (occurring in 20-60% of all patients)
Fibrosis (thickening) of soft tissue in area of treatment
Nausea and Vomiting
Elevated Liver Enzymes
Least Likely (occurring in 0-5%)
An ulcer can form at the site of treatment which may be slow to heal (Temporary)
Effects on voice quality (can be Permanent)
Depending on the specific area treated, you may also experience difficulty swallowing and eating
which would be temporary. If your treated area involves your airway, you might also have difficulty
breathing from the breakdown of tissue, so your doctor will keep you in the hospital overnight to
observe you. You may also be given medication and extra oxygen to breathe if your doctor decides it
would be best for you.
It is possible that patients given the light dose in 2 sessions may be more likely to have side effects, but
the types of side effects are expected to be the same for both groups.
Reproductive Risks
There could be serious harm from Levulan® to unborn children or children who are breast-feeding,
and it could also jeopardize the health of the mother. In addition, it is possible that harmful side effects
from treatment with PDT and Levulan® that are not known yet could occur to both the mother and
unborn or breast-feeding child. For this reason, if you are pregnant, you will inform the study doctor
and understand that you will not be included in the study.
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If you are a woman of childbearing potential, you will be given a pregnancy test before the study. You
must use appropriate contraceptive methods starting at least 14 days prior to the start of the study and
for at least 6 months afterwards. Appropriate contraceptive methods include abstinence or the
following double-barrier methods: diaphragm and condom, intrauterine device and condom, sponge
and condom, or spermicide and condom. If you become pregnant while on this study, you must notify
one of the study doctors immediately so that your treatment alternatives can be discussed.
You (both men and women) must use adequate birth control measures to prevent pregnancy while
participating in this study. If you are unwilling to use adequate birth control measures to prevent
pregnancy, you may not participate in this study.
What are the benefits to taking part in the study?
If you take part in this study, there may or may not be direct medical benefit to you. We hope the
information learned from this study will benefit other patients with precancerous lesions of the head
and neck cancer in the future.
What other options are there?
You may choose to not participate in this study. Other treatments that could be considered for your
condition may include the following: 1) external radiation therapy only; 2) surgery only; 3) surgery
combined with external radiation therapy; or, 4) no treatment at all. With the latter choice, your lesion
could continue to grow and could progress to cancer over the course of several years. However, there
is a significant chance your lesion may not progress to cancer even if you do nothing.
Your doctor can tell you more about your condition and the possible benefits of the different available
treatments. Please talk to your regular doctor about these and other options.
What about confidentiality?
All information collected in this study will be kept strictly confidential, except as may be required by
law. You further understand that the investigator, DUSA pharmaceuticals, representatives of the
University of Pennsylvania, Virginia Mason University and government regulatory agencies such as
the Food and Drug Administration, will have access to data that identifies you by name. You will not
be identified by name in any reports or publications resulting from the study.
What are the costs of participating?
The study drug, Levulan®, is being provided free of charge by DUSA Pharmaceuticals. The light
treatment will performed at no cost to you.
Routine blood tests and exams will be done to evaluate the effects of treatment. There may also be
additional testing and procedures required by this study for research purposes. These additional tests
may increase your medical bills although the impact will be dependent on your insurance company. If
injury occurs as a result of this research, treatment will be available. The use of medication to help
control side effects could result in added costs. This institution is not financially responsible for the
treatment of side effects caused by the study treatment. You will not be reimbursed for medical care
other than what your insurance carrier may cover. You will not be paid for your participation in this
research study.
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Photodynamic Therapy for Pre-Malignant Head and Neck Tumors
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What if new information is discovered?
You will be told of any significant new findings developed during the course of this study that may
relate to your willingness to continue your participation.
What are your rights as a participant?
Your participation in this study is voluntary. You may refuse to participate or may discontinue
participation at any time during the entire duration of the study without penalty or loss of benefits to
which you are otherwise entitled. If you terminate your participation, no prejudice will be shown
toward you for medical care or participation in future research studies. In addition, your participation
may be terminated by the investigator or the sponsor without regard to your consent if it is in your best
interest, you need additional medication, violate the study plan, or experience a study-related injury.
Any time your participation is terminated you will be asked to follow-up with your doctors and to
undergo the routine procedures outlined above (history, physical examination, blood tests) for your
safety. There are other reasons why you may not be permitted to participate in this study. The study
doctor or his/her staff will discuss these with you.
Injury/complications
You understand that in the event of any physical injury resulting from research procedures, medical
treatment will be provided without cost to you, but financial compensation is not otherwise available
from the University of Pennsylvania. You or your third party payer, if any, may be billed for medical
expenses associated with this study if they are deemed medically necessary and such expenses would
have been incurred independent of the study, or if your third party payer agrees in advance to pay for
such expenses.
Whom do you call if you have questions or problems?
For questions about the study or a research-related injury, contact the researchers Dr. Harry Quon at
(215)614-0392, Dr. Stephen Hahn at (215)662-7296, Dr. Robert Lustig at (215)349-8429, Dr. Ara
Chalian at (215) 345-5559, Dr. Bert O’Malley, Jr. at (215)349-538, or Dr. Gregory Weinstein at
(215)349-5390.
For questions about your rights as a research participant, contact the Director of Regulatory Affairs at
the University of Pennsylvania Institutional Review Board by telephoning (215) 898-2614.
You have read the above and understand this consent form. Your questions have been answered. You
voluntarily consent to participate.
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Photodynamic Therapy for Pre-Malignant Head and Neck Tumors
Consent Form
Name of Patient
Signature of Patient
Date
Name of Person Obtaining Consent
Signature of Person Obtaining Consent
Date
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