Clinical trial: NCT01835626
Section: Alternatives
Subsections: Are There Benefits To Taking Part In The Study?|What Other Choices Do I Have If I Do Not Take Part In This Study?

Taking part in this study may or may not make your health better. While doctors hope that vismodegib and radiation will be more useful against your cancer compared to the usual treatment, there is no proof of this. We do know that the information from this study will help doctors learn more about vismodegib and radiationas a treatment for cancer. This information could help future cancer patients.

Your other choices may include:  
Getting treatment or care for your cancer without being in a study - alternative treatment options such as vismodegib or radiation therapy alone. Both are available off-study.  
Taking part in another study Getting comfort care, also called palliative care - this type of care helps reduce pain, tiredness, appetite problems and other problems caused by the cancer; comfort care does not treat the cancer directly, it works to improve how you feel and keep you as active and comfortable as possible Getting no treatment
Your physician will discuss these other options with you. Please talk to your doctor about your choices before deciding if you will take part in this study.
Clinical trial: NCT01835626
Section: Confidentiality
Subsections: Will My Medical Information Be Kept Private?

We will do our best to make sure that the personal information in your medical record is kept private. However, we cannot guarantee total privacy. Your personal information may be given out if required by law. If information from this study is published or presented at scientific meetings, your name and other personal information will not be used.  
Organizations that may look at and/or copy your medical records for research, quality assurance, and data analysis include:
Genentech/Roche Pharmaceuticals and their authorized representatives UCSF Committee on Human Research The National Cancer Institute (NCI) and other government agencies, e.g., the Food and Drug Administration (FDA), involved in overseeing research UCSF Helen Diller Family Comprehensive Cancer Center The University of California Collaborator sites: Memorial Sloan Kettering
Participation in research may involve a loss of privacy, but information about you will be handled as confidentially as possible. A medical record will be created because of your participation in this study. Your consent form and some of your research test results will be included in this record. Therefore, your other doctors may become aware of your participation. Hospital regulations require that all health care providers treat information in medical records confidentially.
Clinical trial: NCT01835626
Section: Duration of Study Involvement
Subsections: How Many People Will Take Part In This Study?|Before You Begin The Main Part Of The Study...|Follow-Up Visits|How Long Will I Be In The Study?

Up to 24 people may participate in the study. About 20 people will take part in this study at UCSF, San Francisco General Hospital, and the San Francisco VA Medical Center.

You will need to have the following exams, tests or procedures to find out if you can be in the main part of the study. These exams, tests or procedures are part of regular cancer care and may be done even if you do not join the study. You will also have some procedures that are only being done because you are in the study. These are called research procedures and are noted in the list of procedures below. If you have had some of them recently, they may not need to be repeated. This will be up to your study doctor. The total time needed to complete all screening tests and procedures is approximately 8 hours.

The study team will ask you to return to the clinic at 3, 6, and 12 months (+/- 2 weeks) after the end of study visit. Each visit will take about 4 hours. You will have the following procedures.  
Physical examination including weight Vital signs Performance Status  
  
Evaluation of adverse events Concomitant medications Blood (about 2 teaspoons) will be drawn for routine safety tests Urine or blood pregnancy test - if a woman of childbearing age - 3 and 6 month visits only Imaging (CT or MRI) of head and neck for tumor assessment - only at 6 month visit Imaging (CT) of chest or chest x-ray - if clinically indicated, only at 6 month visit If you have visible tumors on your body, your study doctor will take measurements of the tumors The following procedures will be done for research:
Skindex-16 survey If you have visible tumors on your body, photographs will be taken of the lesion.
After 1 year, the study team would like to keep track of your medical condition for 1 more year. We would like to do this by calling or reviewing your medical record every 3 months to see how you are doing. Keeping in touch with you and checking on your condition helps us look at the long-term effects of the study.  
Study location: All study procedures will be done at the Helen Diller Family Comprehensive Cancer Center at UCSF or San Francisco General Hospital.

You will receive vismodegib for up to 21 weeks (approximately 5.5 months) and radiation therapy for seven weeks during week 15-21 of vismodegib therapy. You will continue to receive study treatment as long as your disease does not progress or you do not have severe side effects, you experience any bad side effects, you decide to withdraw your consent to participate in this study, or the study is closed. After you are finished taking the treatment, the study doctor will ask you to visit the office for follow-up exams within 8-12 weeks and then 3, 6, and 12 months (+/- 2 weeks) later. After one year, to follow up on your health status, we would like to call or review your medical records every 3 months for up to 1 more year to see how you are doing. Keeping in touch with you and checking on your condition helps us look at the long-term effects of the study. Even if your disease has progressed, the study team would like to continue to monitor your health outcomes. Please let the study doctor know if you do not want to participate in this portion of the study.
Clinical trial: NCT01835626
Section: Participant's Rights
Subsections: What Are My Rights If I Take Part In This Study?

Taking part in this study is your choice. You may choose either to take part or not to take part in the study. If you decide to take part in this study, you may leave the study at any time. No matter what decision you make, there will be no penalty to you and you will not lose any of your regular benefits. Leaving the study will not affect your medical care. You can still get your medical care from our institution. We will tell you about new information or changes in the study that may affect your health or your willingness to continue in the study. In the case of injury resulting from this study, you do not lose any of your legal rights to seek payment by signing this form.
Clinical trial: NCT01835626
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: What Side Effects Or Risks Can I Expect From Being In The Study?|Risks And Side Effects Related To Vismodegib Likely (Seen In More Than 10% Of Patients) Muscle Spasms|Less Likely (Seen In 1%-10% Of Patients)|Risks And Side Effects Related To Radiation Likely|Less Likely, But Serious Effects|Risks Related To Study Procedures|Chest X-Ray Risks: See Radiation Risks Above.|What Happens If I Am Injured Because I Took Part In This Study?

You may have side effects while on the study. Everyone taking part in the study will be watched carefully for any side effects. However, doctors don't know all the side effects that may happen. Side effects may be mild or very serious. Your health care team may give you medicines to help lessen side effects. Many side effects go away soon after you stop taking vismodegib and radiation. In some cases, side effects can be serious, long lasting, or may never go away.  
There also is a risk of death.  
Handling vismodegib and having contact with any urine, feces or vomit from patients receiving vismodegib may pose some risk to you and your caregivers. To avoid exposure to vismodegib and any associated risks, you and your family members/caregivers will be educated by a member of the study team on how to safely handle, properly dispose of, and clean products that may be contaminated with vismodegib.  
You should talk to your study doctor about any side effects that you experience while taking part in the study.

Hair loss Taste changes, lack of taste function Weight loss Fatigue or tiredness Nausea or the urge to vomit Diarrhea Loss of appetite Constipation Vomiting Joint aches Bloated feeling (dyspepsia) Second primary malignancies Squamous cell carcinoma Abdominal/upper abdominal pain

Monthly missed periods in females who can become pregnant Low levels of sodium in the blood (may cause nausea, lethargy, muscle spasms, or seizures)
Low potassium levels (may cause irregular heartbeat and breakdown of muscles)
Higher than normal blood level of urea or other nitrogen-containing compounds in the blood (may cause loss of appetite, lethargy, and mental slowness)
Lack of energy (asthenia) Dehydration Pain in extremities Loss of eyelashes/eyebrows (madarosis) Abnormal hair growth Death/sudden death/cardiac death Bone fracture Venous thromboembolic events Fainting (syncope)

Sores in the mouth and/or throat which can be painful and make it very difficult to chew and or swallow foods Mouth dryness Changes in taste and/or smell that may be permanent Thick saliva Hoarseness Tanning or redness and/or irritation of the skin in the head and neck area being treated with radiation Ear pain and/or pressure Fatigue Weight loss Permanent hair loss in the area treated with radiation Loss of teeth, or cavities in the teeth, if strict dental care is not followed and/or hypersensitivity of teeth

Decrease in function of the thyroid gland that may require you to take thyroid replacement medicine to prevent you from feeling tired or sleepy Serious damage to the spinal cord, nerves in the neck, jawbone, voice box, skin, or other parts of the head and neck that may require a major operation to correct and, rarely, can even be life threatening Temporary pain or scarring around nerves in the shoulder that could cause numbness and/or weakness Breathing problems Difficulty with swallowing and eating for which you might need a long term or permanent feeding tube; possibility of inhaling food and/or liquids into the lungs - which could also result in pneumonia.  
Serious ear infections and/or hearing loss Damage to the spinal cord leading to permanent weakness and/or symptoms like a
"stroke" Permanent hair loss (of the face/chin/neck) Hepatic enzyme increased Blood creatinine phosphokinase increased Aspartate aminotransferase increased Blood alkaline phosphatase increased Pain on one's side between ribs and hip (flank pain) Pain in muscles and bones (musculoskeletal pain) Back pain Muscle pain Musculoskeletal chest pain

Surgery and Radiation risk: If your basal cell carcinoma is advanced, if the disease is left untreated or recurs in the same location after surgery or radiotherapy, it may advance further into surrounding areas such as sensory organs (ears, nose and eyes), bone, or other tissues such as the brain. Depending on the location of the lesion, some cases of advanced BCC can be disfiguring, and treatment with surgery or radiation can lead to the loss of sensory organs and functions such as eyesight or hearing. However these consequences are from the disease or from the surgery/radiation not from vismodegib.  
Study drug combination risks: The side effects of the combination of vismodegib and radiation are not yet known. Combining vismodegib with radiation to the head and neck can increase the effectiveness of radiation therapy on your cancer, but may increase the side effects of the radiation on normal tissue in the treatment area. You will be monitored closely for side effects and your doctor may change your medications if it appears that this combination is causing serious side effects. You should tell your doctor about any side effects you experience while on this study. When additional information about side effects is known, you will be notified of any further study drug related effects.  
Blood Drawing (venipuncture) risks: Drawing blood may cause temporary discomfort from the needle stick, bruising, and infection.  
Radiation (X-ray) risks: As a result of participating in this study, you will receive a significant amount of radiation. The amount is similar to that received in many standard x-ray procedures, but is far more than you would receive from natural daily exposure or in the normal course of treatment, and carries at least a theoretical risk. If you are especially concerned with radiation exposure, you should discuss this with the researchers.

CT scan risks: CT scans involve the risks of radiation (see above). In addition, if contrast material (iodine dye) is used, there is a slight risk of developing an allergic reaction, from mild (itching, rash) to severe (difficulty breathing, shock, or rarely, death). The contrast material may also cause kidney problems, especially if you are dehydrated or have poor kidney function. The study doctors will ask you about any allergies or related conditions before the procedure. If you have any of these problems, you may not be allowed to have a CT scan.  
Having a CT scan may mean some added discomfort for you. In particular, you may be bothered by feelings of claustrophobia when placed inside the CT scanner, or by lying in one position for a long time. If contrast material is used, you may feel discomfort when it is injected. You may feel warm and flushed and get a metallic taste in your mouth. Rarely, the contrast material may cause nausea, vomiting or a headache.  
PET/CT scan risks: The PET/CT scan exposes your body to radiation, see radiation risk above. The radiation levels come from a tracer which is a radioactive chemical injected into a vein in your arm. The tracer lets the doctor see how your cells are functioning and the radiation levels are very low. You may have an allergic reaction to the chemical used in the scan. For some patients, having to lie still on the scanning table for the length of the procedure may cause some discomfort or pain. After the scan your arm may be a little bit sore or have some redness where the IV was placed in your arm. The radioactive solution does not remain in your system for a long period of time. However, you should wait 2 hours before holding an infant or getting close to a pregnant woman to avoid exposing them to radiation. You should drink fluids after the scan to help remove the solution from your system.  
MRI risks: Because the MRI machine acts like a large magnet, it could move iron-containing objects in the MRI room during your examination, which in the process could possibly harm you. Precautions have been taken to prevent such an event from happening; loose metal objects, like pocket knives or key chains, are not allowed in the MRI room. If you have a piece of metal in your body, such as a fragment in your eye, aneurysm clips, ear implants, spinal nerve ICF 02/22/2017 Protocol 11/07/2016 PAGE 9 OF 14 CC\#122011 Sue S. Yom, MD, and Roy Grekin, MD  
  
stimulators, or a pacemaker, you will not be allowed into the MRI room and cannot have an MRI.  
Having an MRI may mean some added discomfort for you. In particular, you may be bothered by feelings of claustrophobia and by the loud banging noise during the study. Temporary hearing loss has been reported from this loud noise. This is why you will be asked to wear ear plugs. At times during the test, you may be asked to not swallow for a while, which can be uncomfortable. Because the risks to a fetus from MRI are unknown, pregnant women must not participate in this study.  
Contrast agent (gadolinium) risks: A few side effects of gadolinium injection such as mild headache, nausea, and local pain may occur. Rarely (less than 1% of the time) low blood pressure and lightheadedness occurs. This can be treated immediately with intravenous fluids.  
Very rarely (less than one in one thousand), patients are allergic to gadolinium. These effects are most commonly hives and itchy eyes, but more severe reactions have been seen which result in shortness of breath.  
Patients with severe kidney disease sometimes have a bad reaction to gadolinium contrast. The condition is called nephrogenic systemic fibrosis (NSF). It can cause skin to tighten or scar and can damage internal organs. Sometimes it can be life-threatening. There are no reports of NSF in patients with normal kidney function. Before you have a MRI scan requiring an injection of gadolinium contrast, you will have a blood test in order to check the function of your kidneys. Based on your medical history and the results of the test, a doctor will decide whether it is safe for you to undergo the MRI scans.  
Tumor biopsy risks: The general risks associated with this procedure are pain, discomfort, infection, bleeding and injury to organs nearby.  
Reproductive risks: You should not become pregnant or father a baby while on this study because the drugs in this study can affect an unborn baby.  
Women should not breastfeed a baby while on this study, or for 24 months after completing therapy. It is important to understand that you need to use birth control while on this study. Women of childbearing age are required to use two forms of acceptable contraception (including one acceptable barrier method with spermicide) during treatment with vismodegib and for 24 months after completing therapy.  
Men must agree not to donate sperm and are required use condoms at all times, even after a vasectomy, during sexual intercourse with pregnant partners or female partners of childbearing age during treatment with vismodegib and for 3 months after the last dose. Vismodegib is present in semen. It is not known if the amount of vismodegib in semen can cause embryo-fetal harm. Check with your study doctor about what kind of birth control methods to use and how long to use them. Some methods might not be approved for use in this study.  
Unknown Risks: The experimental treatments may have side effects that no one knows about yet. The researchers will let you know if they learn anything that might make you change your mind about participating in the study.  
Blood Donation: Do not donate blood or blood products while on this study and for 24 months after the last dose of vismodegib.  
For more information about risks and side effects, ask your study doctor.

It is important that you tell your study doctor Sue S. Yom, MD or Roy Grekin, MD if you feel that you have been injured because of taking part in this study. You can tell her in person or call her
.  
Treatment and Compensation for Injury: If you are injured as a result of being in this study, the University of California will provide necessary medical treatment. The costs of the treatment may be billed to you or your insurer just like any other medical costs, or covered by the University of California or Genentech, depending on a number of factors. The University and the study sponsor do not normally provide any other form of compensation for injury. For further information about this, you may call the office of the Committee on Human Research at 415476-1814.
Clinical trial: NCT01835626
Section: Procedures
Subsections: What Will Happen If I Take Part In This Research Study? Study Treatment|Skindex-16 Survey During The Main Part Of The Study...|When You Are Finished Receiving Vismodegib And Radiation Therapy… End Of Treatment Visit

Vismodegib will be taken daily, once a day on an empty stomach either 1 hour before or 2 hours after meals for 12 weeks, then for 1-14. days as required until the start of radiation therapy. You should take the study drug at approximately the same time each day. You will be given a supply of vismodegib on Week 1, Day 1 to last until your next study visit. You will be asked to keep a record of each dose of vismodegib you take. After 12 weeks, you will be evaluated again to make sure you are still eligible to participate in the study. If you are eligible to continue, you will continue taking vismodeib daily as before for another 7 weeks while you receive radiation therapy.  
  
Radiation therapy will be started after you have finished taking vismodegib for 12 weeks. You will receive radiation once a day, Monday through Friday, for 7 weeks. Each radiation treatment may take up to 30 minutes.

If the exams, tests and procedures show that you can be in the main part of the study, and you choose to take part, then you will need the following tests and procedures. Each visit will take less than 1 hour. You will start taking vismodegib on week 1, day 1 and continue to take it once a day. You will be given your supply once you have completed all of the screening tests.

You will have an End of treatment visit within 8 -12 weeks of the last dose of vismodegib and radiation therapy. The visit will take about 4 hour(s) and the following tests and procedures will occur:  
Physical examination including weight Vital signs Performance status Evaluation of adverse events Concomitant medications Blood (about 2 teaspoons) will be drawn for routine safety tests Urine or blood pregnancy test - if a woman of childbearing age Imaging (CT or MRI) of head and neck for tumor assessment Imaging (CT) of chest or chest x-ray - if clinically indicated If you have visible tumors on your body, your study doctor will take measurements of the tumors
The following procedures will be done for research:
Skindex-16 survey If you have visible tumors on your body, photographs will be taken of the lesion.
Clinical trial: NCT01835626
Section: Purpose of Research
Subsections: Why Is This Study Being Done?

Chemotherapy, radiation therapy, and surgery are standard treatments for basal cell carcinoma at most institutions. The purpose of this study is to determine whether adding vismodegib to radiation (chemoradiotherapy) is safe and tolerable. The purpose of this study is to assess the safety and tolerability of combined radiation therapy and vismodegib. This combination may increase the chances of the tumors being destroyed or unable to spread to other parts of the body in people with locally advanced basal cell carcinoma of the head and neck.  
Vismodegib has been approved by the US Food and Drug Administration (FDA) for the treatment of basal cell carcinoma. It may delay the growth of tumor cells. In previous studies of vismodegib in humans with basal cell carcinoma, vismodegib has shown an anti-tumor effect. The combination of vismodegib and radiation therpay is considered experimental; that means this combination has not been approved by the FDA.  
Genentech, a member of the Roche group, is providing funding to UCSF to conduct the study.  
Genenetch, the manufacturer of study drug, will also provide the study drug at no cost to study participants.
Clinical trial: NCT01835626
Section: Voluntary Participation
Subsections: Consent

You have been given copies of this consent form and the Experimental Subject's Bill of Rights to keep. You will be asked to sign a separate form authorizing access, use, creation, or disclosure of health information about you.  
PARTICIPATION IN RESEARCH IS VOLUNTARY. You have the right to decline to participate or to withdraw at any point in this study without penalty or loss of benefits to which you are otherwise entitled.  
If you wish to participate in this study, you should sign below.
Clinical trial: NCT01835626
Section: Withdrawal from Study
Subsections: Can I Stop Being In The Study?

Yes. You can decide to stop at any time. Tell the study doctor if you are thinking about stopping or decide to stop, they will tell you how to stop safely. It is important to tell the study doctor if you are thinking about stopping so any risks from the vismodegib and radiation therapy can be checked by your doctor. Another reason to tell your doctor that you are thinking about stopping is to talk about what follow-up care and testing could be most helpful for your cancer treatment. The study doctor may stop you from taking part in this study at any time if they believe it is in your best interest, if you do not follow the study rules, or if the study is stopped.