Clinical trial: NCT02367859
Section: Alternatives
Subsections: Alternatives

Alternatives to taking part in this study include having surgery without receiving dabrafenib or trametinib, taking part in another study or not joining a clinical trial at all. Please speak to your study doctor about these and other alternatives.
Clinical trial: NCT02367859
Section: Confidentiality
Subsections: Confidentiality|Authorization To Use Your Health Information For Research Purposes|What Personal Information Will Be Obtained, Used Or Disclosed?|Who May Use Or Disclose The Information?|Who May Receive Or Use The Information?|When Will My Authorization Expire?|Will Access To My Medical Record Be Limited During The Study?

The results of this research study may be presented at scientific or medical meetings or published in scientific journals. Your identity and/or your personal health information will not be disclosed except as authorized by you or as required by law. However, there is always some risk that even de-identified information might be re-identified.  
  
  
  
  
Protocol Title: A Pilot Study of Dabrafenib and Trametinib for Patients with BRAF-mutated Ameloblastoma Patient information may be provided to Federal and other regulatory agencies as required. The Food and Drug Administration (FDA), for example, may inspect research records and learn your identity if this study falls within its jurisdiction. Depending on your medical needs, photographs of the inside of your eyes (retinas) may be taken, to check for, or help manage the visual side effects of the study drugs. These photographs will not visually identify you, other than in the manner than other medical records and scans identify you. These photographs will only be used for the purposes of this study. The purpose of this research study is to obtain data or information on the safety and effectiveness of dabrafenib and trametinib; the results will be provided to the sponsor and drug supplier Novartis, Inc; the Food and Drug Administration and other US federal agencies; and governmental agencies in other countries where the study drugs may be considered for approval.  
  
  
Protocol Title: A Pilot Study of Dabrafenib and Trametinib for Patients with BRAF-mutated Ameloblastoma

Because information about you and your health is personal and private, it generally cannot be used in this research study without your written authorization. If you sign this form, it will provide that authorization. The form is intended to inform you about how your health information will be used or disclosed in the study. Your information will only be used in accordance with this authorization form and the informed consent form and as required or allowed by law. Please read it carefully before signing it.

Your health information related to this study, may be used or disclosed in connection with this research study, including, but not limited to: your name and initials; address; phone number(s); date of birth; age; sex; race; ethnicity; Social Security Number; Medicare ID number; and medical record number (MRN). During the study, researchers will also obtain information about your medical history and medical diagnoses, including family medical history, current and past medications or therapies, physical examination results, laboratory test results (including blood, urine and pregnancy tests), results of procedures (such as CT or MRI scans) and medical reports (such as pathology reports). The researchers will also get information from your medical records.

The following parties are authorized to use and/or disclose your health information in connection with this research study:
The Protocol Director, Dr A Dimitrios Colevas  
The Stanford University Administrative Panel on Human Subjects in Medical Research and any other unit of Stanford University as necessary Colevas / IRB-32275 ICF 5 December 2018 (PA8)
Research Staff

The parties listed in the preceding paragraph may disclose your health information to the following persons and organizations for their use in connection with this research study:  
The Office for Human Research Protections in the US Department of Health and Human Services (HHS)
The Food and Drug Administration The National Institutes of Health (NIH) The US Centers for Medicare & Medicaid Services (CMS), the agency responsible for administration of the Medicare program Novartis and it's authorized agents  
  
  
  
  
  
Protocol Title: A Pilot Study of Dabrafenib and Trametinib for Patients with BRAF-mutated Ameloblastoma  
Governmental agencies in other countries where the study drugs may be considered for approval Colevas / IRB-32275 ICF 5 December 2018 (PA8)
Your information may be re-disclosed by the recipients described above, if they are not required by law to protect the privacy of the information.

Your authorization for the use and/or disclosure of your health information will end on January 1, 2064, or when the research project ends, whichever is earlier.

To maintain the integrity of this research study, you may not have access to any health information developed as part of this study until it is completed.  
At that point, you would have access to such health information if it was used to make a medical or billing decision about you (eg, if included in your official medical record).  
___________________________________________ Printed Name of Participant  
___________________________________________ ____________ Signature of Participant Date
___________________________________________ If *needed*: Printed Name of LAR  
___________________________________________ ____________
Signature of LAR Date
___________________________________________ LAR's Authority to Act for Participant
(eg, parent, guardian, or conservator) NOTE: If using the Short Form Consent process for informed consent in another language pursuant to an "Alteration of HIPAA Authorization," neither the participant nor their LAR should sign the HIPAA "Authorization To Use Your Health Information For Research Purposes" above.  
  
  
  
  
Protocol Title: A Pilot Study of Dabrafenib and Trametinib for Patients with BRAF-mutated Ameloblastoma
Clinical trial: NCT02367859
Section: Participant Responsibilities
Subsections: Participant Responsibilities

As a participant, your responsibilities include:  
Follow the instructions of the Protocol Director and study staff.  
Tell your doctor now if:
o You have had cancer in the past o You are being treated for high blood pressure. o You have had an irregular heartbeat; heart failure; shortness of breath; swelling in your legs; or tiredness  
Protocol Title: A Pilot Study of Dabrafenib and Trametinib for Patients with BRAF-mutated Ameloblastoma  
Colevas / IRB-32275 ICF 5 December 2018 (PA8)
Contact your Study Doctor or the Study Team immediately if you experience:
o Fever o Severe abdominal pain or sick to your stomach o Not wanting to eat
(loss of appetite)
o Blurry vision o Extreme tiredness o Fainting o Change in vision o Yellow eyes or skin o Itching o Easy bruising o Dark urine o Confusion Take the study drug as instructed.  
Keep your study appointments. If it is necessary to miss an appointment, please contact the Protocol Director or research study staff to reschedule as soon as you know you will miss the appointment.  
Tell the Protocol Director or research study staff about any side effects, doctor visits, or hospitalizations that you may have.  
Tell the Protocol Director or research staff if you believe you might be pregnant or gotten your partner pregnant.  
Keep the study drug in a safe place, away from children and for your use only.  
Ask questions as you think of them.  
Tell the Protocol Director or research staff if you change your mind about staying in the study.
Clinical trial: NCT02367859
Section: Participant's Rights
Subsections: Participant'S Rights|Experimental Subject'S Bill Of Rights

You should not feel obligated to agree to participate. Your questions should be answered clearly and to your satisfaction. If you decide not to participate, tell the Protocol Director. You will be told of any important new information that is learned during the course of this research study, which might affect your condition or your willingness to continue participation in this study.

As a research participant you have the following rights. These rights include but are not limited to the participant's right to:  
be informed of the nature and purpose of the experiment; be given an explanation of the procedures to be followed in the medical experiment, and any drug or device to be utilized; be given a description of any attendant discomforts and risks reasonably to be expected; be given an explanation of any benefits to the subject reasonably to be expected, if applicable; be given a disclosure of any appropriate alternatives, drugs or devices that might be advantageous to the subject, their relative risks and benefits; be informed of the avenues of medical treatment, if any available to the subject after the experiment if complications should arise; be given an opportunity to ask questions concerning the experiment or the procedures involved; be instructed that consent to participate in the medical experiment may be withdrawn at any time and the subject may discontinue participation without prejudice; be given a copy of the signed and dated consent form; and be given the opportunity to decide to consent or not to consent to a medical experiment without the intervention of any element of force, fraud, deceit, duress, coercion or undue influence on the subject's decision.  
Colevas / IRB-32275 ICF 5 December 2018 (PA8)  
  
| Approval Date: December 18, 2018 Expiration Date:   |
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Protocol Title: A Pilot Study of Dabrafenib and Trametinib for Patients with BRAF-mutated Ameloblastoma Signing your name means you agree to be in this study and that you will receive a copy of this signed and dated consent form. _______________________________________________ Printed Name of Participant  
_______________________________________________ ____________ Signature of Adult Participant Date If needed:  
_______________________________________________ Printed Name of Legally Authorized Representative (LAR)  
_______________________________________________ ____________ Signature of LAR Date  
_______________________________________________ LAR's Authority to Act for Participant (eg, parent, guardian, or conservator) _______________________________________________ ____________ Signature of Person Obtaining Consent Date  
| Printed Name of Person Obtaining Consent (POC)   |
|--------------------------------------------------|  
  
  
Protocol Title: A Pilot Study of Dabrafenib and Trametinib for Patients with BRAF-mutated Ameloblastoma The following witness line is to be signed only if the consent is provided as a summary form and accompanied by a short-form foreign language informed consent document.
Clinical trial: NCT02367859
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Risks:|If You Feel Discomfort At Any Time, Notify The Operator And You Can Discontinue The Exam At Any Time. Your Tissue / Data Samples For Research And Genetic Testing|Possible Risks, Discomforts And Inconveniences|Dabrafenib + Trametinib Combination Side Effects:|Common Dabrafenib + Trametinib Side Effects, Some May Be Serious|Common Dabrafenib + Trametinib Side Effects, Some May Be Serious|Common Dabrafenib + Trametinib Side Effects, Some May Be Serious|Common Dabrafenib + Trametinib Side Effects, Some May Be Serious|Dabrafenib Side Effects:|Very Common Dabrafenib Side Effects, Some May Be Serious In 100 People Receiving Dabrafenib, 10 Or More (≥ 10%; 1 Or More Of Every 10) May Have: Diarrhea Nausea Vomiting Decreased Appetite Skin Effects Including: O Rash O Thickening Of The Skin (Hyperkeratosis)|Very Common Dabrafenib Side Effects, Some May Be Serious|Common Dabrafenib Side Effects, Some May Be Serious|Uuncommon (Rare) Dabrafenib Side Effects, Some May Be Serious|Vvery Rare Dabrafenib Side Effects, Some May Be Serious|Oother Dabrafenib Side Effects, Some May Be Serious :|Trametinib Side Effects: Very Common Trametinib Side Effects, Some May Be Serious|Common Trametinib Side Effects, Some May Be Serious In 100 People Receiving Trametinib, Between 1 And 10 People (1 To 10%) May Have:|Vvery Rare Trametinib Side Effects, May Be Serious|Reproductive Risks

Magnetic fields do not cause harmful effects at the levels used in the MRI machine. However, the MR scanner uses a very strong magnet that will attract some metals and affect some electronic devices. If you have a cardiac pacemaker or any other biomedical device in or on your body, it is very important that you tell the operator/investigator immediately. As metallic objects may experience a strong attraction to the magnet, it is also very important that you notify the operator of any metal objects (especially surgical clips), devices, or implants that are in or on your body before entering the magnet room.  
All such objects must be removed (if possible) before entering the magnet room. In some cases, having those devices means you should not have an MRI scan performed. In addition, watches and credit cards should also be removed as these could be damaged. You will be provided a way to secure these items. If you have any history of head or eye injury involving metal fragments, if you have ever worked in a metal shop, or if you could be pregnant, you should notify the operator/investigator.

Research using tissues, such as from your tumor, is an important way to try to understand human disease. Sometimes, research may include the testing and study of genes, also known as DNA. This type of testing is also called "genetic analysis" or called "pharmacogenomic research." You are been given this information because the Study Doctors want to include a sample of your tumor in a research project and because they want to save the samples for future research. This research may include trying to make cells from your tumor grow in the laboratory for further study.  
There are several things you should know before participating in this study and allowing your tissues to be studied. This subject is complicated, and there are many considerations. Ask for more information if you do not understand any part of this information. Genes are in every cell of your body. Your genes were inherited from your biological parents and carry instructions for the body to grow, develop, and survive. Genes are made of a substance called DNA. Most genes and DNA are identical among human beings, but there are small variations between different people. These small genetic differences are why people have their own unique characteristics, such hair color, eye color, height, and other characteristics. Some traits affected by genetics are not visible, such why different people have different responses, including side effects, to the same drug, or are more likely to get certain diseases or conditions. The proteins in your body were determined by your genes, and control how your body works. Differences in genes and therefore proteins can affect the way a disease develops, the way drugs act against the disease, or the way your body uses the drugs.  
  
Protocol Title: A Pilot Study of Dabrafenib and Trametinib for Patients with BRAF-mutated Ameloblastoma The purpose of this type of research is to understand the cause of disease, such as cancer, or the body's response to the treatments (such as safety findings or drug level patterns). In this study, the genetic research is being done to help identify individuals who will benefit more from using the study drug when their cancer returns around the same location or occurs in distant organs. to find out if the study medications (or other drugs) are effective against your cancer, why they were or weren't effective, and if there are any characteristics of the cancer that predicted whether or not the drugs would be effective. Agreeing to provide this tumor biopsy sample is optional, and not required to participate in this study. The data from your sample for this genetic research project will be used for research purposes only. The sample and data generated from them will be held by the study team and other researchers for many years. These samples, and the data generated from them, may be shared with other researchers or entered into databases, provided confidentiality is upheld (you are not identified), and they are used only for research on the topics described in this document. The information in these databases may be kept forever, however, information that could directly identify you will not be included in these databases. Information from analyses of your coded samples and your coded medical information will be put into one of the National Institutes of Health (NIH) databases, such as the "database of Genotypes and Phenotypes" (dbGaP at http://www.ncbi.nlm.nih.gov/gap), along with information from the other research participants and will be used for future research. These databases will be accessible by the Internet. Only anonymous information from the analyses will be put in a completely public database, available to anyone on the Internet. No traditionally-used identifying information about you, such as your name; address; telephone number; or Social Security Number, will be put into the public database.  
While the public database will not contain information that is traditionally used to identify you, people may develop ways in the future that would allow someone to link your genetic or medical information in our databases back to you. For example, someone could compare information in our databases with information from you (or a blood relative) in another database and be able to identify you (or your blood relative). It also is possible that there could be violations to the security of the computer systems used to store the codes linking your genetic and medical information to you. However, your privacy is very important to us and we will use safety measures to protect it. Despite all of the safety measures that we will use, we cannot guarantee that your identity will never become known. Although you will be told the results of study tests that are part of your regular medical care, the genetic testing described here will not be used for decisions about your medical care, and there may be no results from this genetic research for  
  
  
  
Protocol Title: A Pilot Study of Dabrafenib and Trametinib for Patients with BRAF-mutated Ameloblastoma many years, therefore the results of the genetic testing may not be given to you, your doctor, or any other staff at the study center.

There are risks, discomforts, and inconveniences associated with any research study. These deserve careful thought. You should talk with the Protocol Director if you have any questions. You may have side effects from the medication or procedures used in this study and they will vary from person to person. Everyone taking part in this study will be watched carefully for any side effects. Stanford University, the study doctor and other doctors do not know all of the side effects that could occur and there may be unknown side effects that could occur. You should talk to your study doctor about any side effects that you have while taking part in this study.

Approximately 3000 study participants have received the combination of dabrafenib and trametinib dimethyl sulfoxide "trametinib" at varying doses in other studies. The side effects listed below are primarily based on a total number of 559 patients studied in two phase 3 trials (MEK115306 and MEK116513). Tell your study doctor if you get any of these, or other, side effects.  
VERY COMMON DABRAFENIB **+ TRAMETINIB SIDE EFFECTS, SOME MAY BE SERIOUS** In 100 people receiving the combination of dabrafenib+trametinib, 10 or more (≥ 10%; 1 or more of every 10) may have:
Fever, which may sometimes be associated with low blood pressure (hypotension),
dehydration; dizziness; and/or fainting.  
Bleeding (hemorrhage). The majority of events reported were mild bleeding events which did not require intervention; however, major bleeding events, defined as symptomatic bleeding in a critical area or organ, and/or fatal bleeding in the brain have been reported.  
Chills Decreased appetite Headache Dizziness Cough Abdominal pain Constipation Diarrhea Nausea Vomiting

In 100 people receiving the combination of dabrafenib+trametinib, between 1 and 10 people (1 to 10%) may have:
A type of skin cancer called squamous cell carcinoma (SCC)
Thickening of the palms and soles, which may be tender or painful with a burning feeling (hand-foot skin reaction)
Skin effects including:
o Thickening of the skin (hyperkeratosis)
o Skin cracking o Warts (papilloma)
o Wart-like growths (seborrheic keratosis) o Skin lesions o Acne-like rash o Scaly patches (actinic keratosis)
o Redness o Rash with pus-filled lesions o Inflammation of the fatty layer under the skin (panniculitis), which can cause red, painful lumps Skin infection (cellulitis)
Dry Mouth Dehydration Night sweats Muscle spasms  
Colevas / IRB-32275 ICF 5 December 2018 (PA8)

In 100 people receiving the combination of dabrafenib+trametinib, between 1 and 10 people (1 to 10%) may have:
Bladder infection Nail problems including pain infection and swelling of the cuticles (paronychia) Low number of platelets (thrombocytopenia), which may cause bleeding and bruising A decrease in white blood cell count (neutropenia) which may affect your ability to fight infection A decrease in red blood cells which may cause tiredness, shortness of breath or dizziness (anemia)
Low blood sodium level often associated with dehydration (hyponatremia) Low phosphate level which may cause muscle weakness (hypophosphatemia) High blood sugar (hyperglycemia)
Decrease in the number of white blood cells found in the blood (leukopenia)
Eye problems such as blurry vision or vision changes Low blood pressure Swelling in an arm or leg as a result of fluid build-up (lymphedema) Facial swelling Shortness of breath (dyspnea)
Redness, swelling or pain in the mouth (stomatitis)
Hair loss Sweating more than usual Kidney failure Swelling of and/or redness and/or pain of the lining inside the mouth or nose or sometimes around the eyes (mucosal inflammation)
Flu-like illness Inflammation of one or more hair follicles (folliculitis)
Increased blood level of protein from the muscle (blood creatine phosphokinase increased)
Abnormal liver tests (blood gamma-glutamyl transferase increased, blood alkaline phosphatase increased) which may mean that your liver is not working normally.  
o This is usually mild and reversible, but it may be serious or life-threatening. o Your study doctor will check liver tests regularly while you receive study treatment.  
Tell your study doctor or study nurse if you have itching, yellowing of the eyes or skin, dark urine, pain or discomfort in the right upper area of your stomach.  
Decreased heart rate (bradycardia) Changes in how well the heart pumps blood (ejection fraction decreased). This may cause an irregular heartbeat; heart failure; shortness of breath; swelling in your legs; or tiredness.  
o Tell your study doctor if you get any of these symptoms. Your study doctor will run tests to check your heart is working properly before and during treatment. It is also important to tell your study doctor about any pre-existing heart conditions.

In 100 people receiving the combination of dabrafenib+trametinib, between 1 and 10 people (1 to 10%) may have:
A type of skin cancer called squamous cell carcinoma (SCC)
Thickening of the palms and soles, which may be tender or painful with a burning feeling (hand-foot skin reaction)
Skin effects including:
o Thickening of the skin (hyperkeratosis)
o Skin cracking o Warts (papilloma)
o Wart-like growths (seborrheic keratosis) o Skin lesions o Acne-like rash o Scaly patches (actinic keratosis)
o Redness o Rash with pus-filled lesions o Inflammation of the fatty layer under the skin (panniculitis), which can cause red, painful lumps Skin infection (cellulitis)
Dry Mouth Dehydration Night sweats Muscle spasms  
Colevas / IRB-32275 ICF 5 December 2018 (PA8)

In 100 people receiving the combination of dabrafenib+trametinib, between 1 and 10 people (1 to 10%) may have:
Bladder infection Nail problems including pain infection and swelling of the cuticles (paronychia) Low number of platelets (thrombocytopenia), which may cause bleeding and bruising A decrease in white blood cell count (neutropenia) which may affect your ability to fight infection A decrease in red blood cells which may cause tiredness, shortness of breath or dizziness (anemia)
Low blood sodium level often associated with dehydration (hyponatremia) Low phosphate level which may cause muscle weakness (hypophosphatemia) High blood sugar (hyperglycemia)
Decrease in the number of white blood cells found in the blood (leukopenia)
Eye problems such as blurry vision or vision changes Low blood pressure Swelling in an arm or leg as a result of fluid build-up (lymphedema) Facial swelling Shortness of breath (dyspnea)
Redness, swelling or pain in the mouth (stomatitis)
Hair loss Sweating more than usual Kidney failure Swelling of and/or redness and/or pain of the lining inside the mouth or nose or sometimes around the eyes (mucosal inflammation)
Flu-like illness Inflammation of one or more hair follicles (folliculitis)
Increased blood level of protein from the muscle (blood creatine phosphokinase increased)
Abnormal liver tests (blood gamma-glutamyl transferase increased, blood alkaline phosphatase increased) which may mean that your liver is not working normally.  
o This is usually mild and reversible, but it may be serious or life-threatening. o Your study doctor will check liver tests regularly while you receive study treatment.  
Tell your study doctor or study nurse if you have itching, yellowing of the eyes or skin, dark urine, pain or discomfort in the right upper area of your stomach.  
Decreased heart rate (bradycardia) Changes in how well the heart pumps blood (ejection fraction decreased). This may cause an irregular heartbeat; heart failure; shortness of breath; swelling in your legs; or tiredness.  
o Tell your study doctor if you get any of these symptoms. Your study doctor will run tests to check your heart is working properly before and during treatment. It is also important to tell your study doctor about any pre-existing heart conditions.

Approximately 9600 cancer patients have been treated with dabrafenib alone or in combination with trametinib. Based on data from ongoing and completed studies, as well as post-marketing reports, the following are possible risks while taking dabrafenib.

between 1 and 10 people (0.1 to 1%) may have:
Allergic reaction New melanomas Skin tags (acrochordon)
Problems with your eyes including:
Retinal detachment Inflammation of the eye (uveitis)
Swelling around the eyes (periorbital edema)
Separation of light sensitive layer of the eye (the retina) from its supporting layers
(retinal pigment epithelial detachment, chorioretinopathy) which can result in blurry vision.  
These types of vision problems often improve, however there is a slight risk that they may not improve and could lead to blindness Heart failure (cardiac failure, left ventricular dysfunction) which means the heart is not able to pump blood properly or it has difficulty filling with blood. It can cause weakness and tiredness, swelling, and shortness of breath.  
Inflammation of the pancreas, a gland that controls blood sugar levels and helps digest food Inflammation of the kidney (may appear as side pain or blood in the urine) (nephritis)
Acute kidney failure Breakdown of muscle, which can lead to symptoms including muscle pain and kidney damage (rhabdomyolysis)
Inflammation of the lung tissue (Pneumonitis or Interstitial lung disease) - may present with symptoms such as shortness of breath, changes in chest CT scan Tell your study doctor about any pre-existing lung problems that you have.  
Tell your study doctor if you have any new or worsening symptoms of lung or breathing problems, including:
shortness of breath cough If your study doctor thinks you have signs or symptoms of impaired lung function, he/she may order more test(s) to further evaluate your lung function Colevas / IRB-32275 ICF 5 December 2018 (PA8)

In 100 people receiving dabrafenib, 10 or more (≥ 10%; 1 or more of every 10) may have:
o Warts (papilloma)
Thickening of the palms and soles, which may be tender or painful with a burning feeling (hand-foot skin reaction, palmar-plantar erythrodysaesthesia syndrome)
Hair loss (alopecia)
Tiredness (fatigue)
Headache Fever (pyrexia), which may sometimes be associated with low blood pressure, dehydration. dizziness and/or fainting Pain or stiffness of joint(s) (arthralgia) Muscle pain (myalgia) Pain in your arms and/or legs Chills Cough Weakness (asthenia)

In 100 people receiving dabrafenib, between 1 and 10 people (1 to 10%) may have:
Low phosphorous level which may cause muscle weakness (hypophosphatemia)
Constipation Flu-like illness Cutaneous squamous cell carcinoma (SCC) of the skin (a type of skin cancer) /
keratoacanthoma / Bowen's disease)
Inflammation of the throat and nasal passage (nasopharyngitis)
High blood sugar (hyperglycemia, may cause increased thirst and frequent urination)
Skin effects including noncancerous skin growths, such as:
o Skin lesions o Skin tags or wart-like growths (acrochordon, seborrhoeic keratosis) o Dry skin o Redness of the skin (erythema)
o Itchy skin (pruritis) o Scaly skin (actinic keratosis)

In *1000* people receiving dabrafenib, between 1 and 10 people (0.1 to 1%) may have:
Inflammation of the pancreas (pancreatitis), a gland that controls blood sugar levels and helps digest food Inflammation of the eye (uveitis), which can infrequently result in blindness. Tell your doctor about any changes in your vision Allergic reaction to dabrafenib which may appear as rash, blisters or fever New melanomas Kidney failure Inflammation of the fatty layer under the skin, which can cause red, painful lumps
(panniculitis)  
Protocol Title: A Pilot Study of Dabrafenib and Trametinib for Patients with BRAF-mutated Ameloblastoma

In *10000* people receiving dabrafenib, between 1 and 10 people (0.1 to 1%) may have::
In a study of patients with melanoma brain metastases there have been reports of side effects in the brain (some of them fatal), including bleeding into the brain and seizures. These events may also be seen in patients with melanoma brain metastases who are not receiving dabrafenib.  
Inflammation of the kidney (may appear as side pain or blood in the urine) (nephritis)

In a study of patients with melanoma brain metastases there have been reports of side effects in the brain (some of them fatal), including bleeding into the brain and seizures. These events may also be seen in patients with melanoma brain metastases who are not receiving dabrafenib.

In 100 people receiving trametinib, 10 or more (≥ 10%; 1 or more of every 10) may have:
Skin rash or acne-like rash:
o Contact your study doctor or study nurse if you are affected, as it is important that this is treated to avoid more severe symptoms Diarrhea o Contact your study doctor or study nurse if you are affected, as it is important that this is treated to avoid dehydration Bleeding (hemorrhage)
o The majority of events reported were mild bleeding events which did not require intervention. Major bleeding events in a critical area or organ, and fatal bleeding in the brain, have also been reported.  
Feeling sick (nausea)
Feeling tired (fatigue)
Swelling of the hands/feet (peripheral edema)
Increase of blood pressure o Tell your study doctor if you have hypertension or are on medications to treat high blood pressure Vomiting Constipation Stomach pain Shortness of breath Cough Dry or itching skin Fever Dry mouth Unusual hair loss or hair thinning COMMON TRAMETINIB SIDE EFFECTS**, SOME MAY BE SERIOUS**
In 100 people receiving trametinib, between 1 and 10 people (1 to 10%) may have:  
Protocol Title: A Pilot Study of Dabrafenib and Trametinib for Patients with BRAF-mutated Ameloblastoma

Visual problems, such as blurry vision, and decreased vision:
o Tell your study doctor about any changes in your vision; your study doctor will send you for eye exam and treatment may need to be interrupted. A blood sample will also be collected if you have vision problem to evaluate the amount of drug in your blood.  
o It is important that you do not drive a car or work with machinery if you are experiencing any visual changes.  
o These symptoms go away in most cases.  
Facial swelling Swelling around the eyes (periorbital edema) Dehydration (low levels of water or fluid)
Swelling of and/or redness and/or pain of the lining inside the mouth or nose
(mucosal inflammation)
Redness, swelling, or pain in the mouth (stomatitis) Irregular heartbeat, shortness of breath, swelling in the legs, and/or tiredness, which may indicate changes in how your heart pumps blood (left ventricular ejection fraction decreased or left ventricular dysfunction).  
o Tell your study doctor if you get any of these symptoms. Your study doctor will run tests to check your heart is working properly before and during treatment. It is also important to tell your study doctor about any pre-existing heart conditions Swelling in the arms or legs as a result of fluid build-up (lymphedema) Decreased red blood cells (anemia)
Increased blood level of a protein from muscle (CPK increased)
Nose bleeding (epistaxis) Redness, chapping, or cracking of the skin Redness, tenderness and possibly painful hands and feet (hand and foot syndrome)
Rash with pus-filled lesions Weakness Inflammation of hair follicles in the skin (folliculitis)
Infection of the skin (cellulitis)
Nail bed changes, nail pain, infection, and swelling of the cuticles (nail disorders, paronychia)
Shortness of breath or changes in chest CT scan, which may indicate inflammation of the lung (pneumonitis)
o Tell your study doctor about any pre-existing lung problems that you have o If you have signs or symptoms of impaired lung function, your study doctor may order more test(s) to further evaluate your lung function.  
Elevated liver enzymes which may suggest damage to the liver o Your study doctor will check liver enzymes regularly while you receive study treatment. Tell your study doctor right away if you experience itching, yellow eyes and/or skin, dark urine, pain, or discomfort in the right upper area of the belly (tummy, stomach).  
Heart rate decreased (bradycardia)  
  
  
  
Protocol Title: A Pilot Study of Dabrafenib and Trametinib for Patients with BRAF-mutated Ameloblastoma  
UUNCOMMON (RARE) TRAMETINIB SIDE EFFECTS**, SOME MAY BE SERIOUS**
In *1000* people receiving trametinib, between 1 and 10 people (0.1 to 1%) may have:
Symptoms like fever, rash, abnormal liver enzymes and visual changes, which may indicate a hypersensitivity / allergic reaction Symptoms like shortness of breath, extreme tiredness, and swelling in ankles & legs, which may indicate that your heart is pumping less efficiently (cardiac failure)
Symptoms such as shortness of breath, changes in chest CT scan, which may indicate that inflammation in the lungs (interstitial lung disease)
o Tell your study doctor about any pre-existing lung problems that you have o If you have signs or symptoms of impaired lung function, your study doctor may order more test(s) to further evaluate your lung function.  
Visual problems (different from above) including:
o Retinal detachment o Separation of the light-sensitive membrane in the back of the eye (the retina) from its supporting layers (retinal pigment epithelial detachment, chorioretinopathy) which can result in blurry vision o Symptoms like headache, nausea and vomiting, or vision problems, which may indicate swelling of the optic nerve (papilloedema)
o Blockage or bleeding of the vein draining the eye, which in severe cases can lead to vision loss (retinal vein occlusion):
o While these types of visual problems often improve, there is a risk that they may not improve.  
o Detailed eye examination is required at the start of the study. If retinal vein occlusion (see above) is identified, you will not be able to participate in this study.  
Colevas / IRB-32275 ICF 5 December 2018 (PA8)

In *10000* people receiving trametinib, between 1 and 10 people (0.1 to 1%) may have::
Symptoms including muscle pain and kidney damage, which may indicate breakdown of muscle tissue (rhabdomyolysis)
In some cases, side effects can be serious, long-lasting, may never go away, and may lead to death. Cases of sudden death have occurred in patients with advanced cancer. Certain problems can be dangerous if not treated quickly; call your study doctor right away if you:
**Feel very tired or faint**
**Feel pain or sick in your stomach and not want to eat**  
**Bruise easily or develop itching**
**Have yellow eyes or skin, or dark urine** **Become confused**
If you experience certain serious problems (such as an allergic reaction, swelling, difficulty breathing, a bad skin rash, liver or kidney damage, or changes in your heart  
  
  
  
  
  
Protocol Title: A Pilot Study of Dabrafenib and Trametinib for Patients with BRAF-mutated Ameloblastoma beat), you may be asked to return to the clinic for more assessments, which may include more blood tests. Your study doctor will explain these tests to you if they are needed. You may also need to stop taking the study drug after talking with your study doctor. You may feel discomfort from some of the procedures during this study. When you give blood or have a cannula inserted in your arm, you may feel faint, or experience mild pain, bruising, irritation or redness at the site, or blockage of veins. In rare cases, you may get an infection or damage to nerves at the site. A cannula is a small tube that stays in your arm so that you will not need a lot of needle sticks when blood is drawn. Study staff will remove the cannula before you leave the clinic.  
When you have your heart monitored, you may have itching or get bruising of the skin where the machine patches are placed. During some of the tests that may be performed on you (MUGA scans, CT scans, or bone scans), you will be exposed to varying amounts of radiation. Please discuss with your study doctor the amount of radiation for each scan if you have questions. During the CT scans, and MRI, you will get dye that will be injected into one of your veins. There is a risk of allergic reaction to the dye. This reaction may be mild (such as a skin rash or hives) to severe (such as breathing difficulties and shock). There is also a risk that the injection of dyes may cause pain, swelling, bruising, irritation or redness at the site, infection at the site of the needle puncture, or feeling faint. Your study doctor will take steps to prevent this from happening, and may recommend medications that may help with these particular side effects.

For **FEMALE** patients: You should not take part in this study if you are pregnant, as problems with the developing fetus may occur based on studies in animals. Mothers should not breastfeed a baby while on this study and for 4 weeks following the last dose of study drug. You should not become pregnant while you are in this study because dabrafenib may affect an unborn baby. If you are a woman who can get pregnant, you will need to have a blood pregnancy test done within 14 days prior to randomization. Women who can get pregnant must agree to use effective contraception for 14 days prior to enrollment, throughout the treatment period and for 6 months after the last dose of study treatment. Check with the study doctor about what kind of birth control methods to use. Women of childbearing potential should be advised that dabrafenib may decrease the efficacy of hormonal contraceptives and an alternative method of contraception, such as barrier methods, should be used. Check with your study doctor about what kind of birth control methods you should use and how long to use them for.  
  
Protocol Title: A Pilot Study of Dabrafenib and Trametinib for Patients with BRAF-mutated Ameloblastoma A double-barrier method includes a condom with spermicide, a diaphragm with spermicide, or a diaphragm and male condom. Another option is to only have intercourse with a partner who has had a vasectomy (surgical sterilization). If you get pregnant during this study, call the study doctor right away. You will not be able to continue in this study if you become pregnant. You may be asked questions later about the pregnancy and the baby. For **MALE** patients: Based on studies in animals, dabrafenib may cause damage to the tissue that makes sperm. This may cause sperm to be abnormal in shape and size and could lead to infertility, which may be irreversible.
Clinical trial: NCT02367859
Section: Procedures
Subsections: Procedures

If you choose to participate, the Protocol Director and his research study staff will take a sample of blood to confirm your eligibility for this study. Once you have signed this informed consent document, the research team will perform the following procedures.
Clinical trial: NCT02367859
Section: Purpose of Research
Subsections: Purpose Of Research|What Is The Purpose Of This Research Study And How Will My Health Information Be Utilized In The Study?

You are invited to participate in a research study of a type of cancer found in the bones supporting your teeth (mandible and maxilla) called ameloblastoma. Ameloblastoma may also be known as "cystosarcoma;" "adamantine epithelioma;" and "adamantinoma." Ameloblastoma is a rare tumor of dental origin. We hope to learn how well pills called dabrafenib and trametinib dimethyl sulfoxide ("trametinib") work for the treatment of these types of tumors. You were selected as a possible participant in this study because you have been diagnosed with an ameloblastoma and your tumor has a mutation in a gene called BRAF. There is strong evidence in other diseases, especially melanoma, that the combination of dabrafenib and trametinib is effective in treating tumors with BRAF mutations, and preliminary evidence in ameloblastoma that the same is true. Your normal medical care for ameloblastoma may include surgical removal of the tumor. Surgery is the standard treatment for these tumors if they are removable, and current therapies have had limited clinical benefit, with partial response being the best reported. It is unclear how much of the mandible and maxilla needs to be removed during surgery to prevent recurrence. Surgery is typically characterized as 2 options: conservative vs radical. Conservative surgery has a high rate of recurrence of the cancer (60 to 90%), and radical surgery tries to ensure that as much tumor as possible is removed, meaning that more tissue surrounding the tumor is removed ("wide margins" or borders), which may result in functional impediments to speech or swallowing, or be potentially-disfiguring. The part of this study that is research (not part of your regular care) are the use of dabrafenib. Dabrafenib and trametinib will be provided at no cost to you.

The results from this research study are expected to be presented at scientific or medical meetings or published in scientific journals. If this treatment proves to demonstrate clinical benefit, physicians may adopt dabrafenib in the future as part of the standard treatment for ameloblastoma. You will not be personally identified in the publications, although representatives of the sponsor and FDA and other international regulatory agencies may need to know who you are.
Clinical trial: NCT02367859
Section: Voluntary Participation
Subsections: Voluntary Participation

Your participation in this study is entirely voluntary. Your decision not to participate will not have any negative effect on you or your medical care. You can decide to participate now, but withdraw your consent later and stop being in the study without any loss of benefits or medical care to which you are entitled. You will be informed of any significant new information about this study or the study drug dabrafenib that might affect your willingness to participate in this research study.
Clinical trial: NCT02367859
Section: Withdrawal from Study
Subsections: If You Decide To Terminate Your Participation In This Study, You Should Notify Dr. A. Dimitrios Colevas At (650) 724-9707.|Withdrawal From Study|If You Decide To Withdraw Your Consent To Participate In This Study, You Should Notify Dr. A. Dimitrios Colevas At (650) 724-9707.|If I Sign, Can I Revoke It Or Withdraw From The Research Later?

This research study is looking for about 5 research participants with BRAF-mutated ameloblastoma. Stanford University expects to enroll all 5 research study participants.  
  
  
  
Protocol Title: A Pilot Study of Dabrafenib and Trametinib for Patients with BRAF-mutated Ameloblastoma

If you first agree to participate and then you change your mind, you are free to withdraw your consent and discontinue your participation at any time. Your decision will not affect your ability to receive medical care for your disease and you will not lose any benefits to which you would otherwise be entitled.

If you withdraw from the study, or the study medication is stopped for any reason, it is important to tell the study doctor so any potential risks from the study drug can be evaluated by your doctor. Another reason to tell your doctor that you are thinking about stopping is to discuss what follow-up care and testing might be most helpful for you. If you decide to stop being in this study or if your study doctor withdraws you from taking part in this study, your study doctor will ask you to come back for a final study visit. The Protocol Director may also withdraw you from the study and the study medication may be stopped without your consent for one or more of the following reasons:  
Failure to follow the instructions of the Protocol Director and study staff.  
The Protocol Director decides that continuing your participation could be harmful to you.  
  
  
Protocol Title: A Pilot Study of Dabrafenib and Trametinib for Patients with BRAF-mutated Ameloblastoma  
Pregnancy.  
Colevas / IRB-32275 ICF 5 December 2018 (PA8)
You need treatment not allowed in the study.  
Your cancer worsens.  
The study is cancelled. Other administrative reasons.  
Unanticipated circumstances.

If you decide to participate, you are free to withdraw your authorization regarding the use and disclosure of your health information (and to discontinue any other participation in the study) at any time. After any revocation, your health information will no longer be used or disclosed in the study, except to the extent that the law allows us to continue using your information (eg, necessary to maintain integrity of research). If you wish to revoke your authorization for the research use or disclosure of your health information in this study, you must write to:
Dr A Dimitrios Colevas, MC 5826 875 Blake Wilbur Drive, 2328 Stanford, California 94305  
  
  
  
Protocol Title: A Pilot Study of Dabrafenib and Trametinib for Patients with BRAF-mutated Ameloblastoma