Clinical trial: NCT03287947
Section: Alternatives
Subsections: Will I Benefit From Participating In This Study?|Information From This Study May Help You And/Or Other People With Your Disease In The Future. What Other Choices Do I Have If I Do Not Take Part In This Study?

The benefits of nintedanib to treat advanced and/or metastatic appendiceal carcinoma are not fully known and it might be that you do not gain any benefit by participating in this research. With our current knowledge and understanding, nintedanib may have the potential to provide benefits to you or others like you, by slowing down the growth and spread of the tumor.

You may choose not to participate in this study and receive routine care, or any standard treatment as recommended by your study doctor, such as other chemotherapy, or participation in other clinical trials. Your study doctor can discuss the alternatives and the risks and benefits of these alternatives with you. Please ask any questions you may have and take as much time as you need to make your decision. If you choose not to take part in this study, that will not harm your relationship with your doctor or with CHS.
Clinical trial: NCT03287947
Section: Confidentiality
Subsections: Will My Medical Information Be Kept Private?

Organizations that may look at and/or copy your medical records for research, quality assurance, and data analysis include:  
- Carolinas HealthCare System (CHS) - Boehringer Ingelheim, the company that manufactures nintedanib - Government agencies, like the Food and Drug Administration (FDA) that are involved in keeping research safe for people
- Other persons/agencies as required by law or allowed by federal regulations
The records of this study will be kept private. In any sort of report we might publish, we will not include any information that will make it possible to identify a patient. Your record for this study may, however, be reviewed and/or photocopied, by Carolinas HealthCare System, or by representatives of the Food and Drug Administration or other government agencies. To that extent, confidentiality is not absolute. A description of this clinical trial will be available on www.ClinicalTrials.gov, as required by U.S. law. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time. To ensure that your information collected for this study will be kept private, your name will not be used whenever possible. A code will be used instead of your name. All of your study data will be kept in a secure location.
Clinical trial: NCT03287947
Section: Duration of Study Involvement
Subsections: After You Complete The Intervention (End Of Treatment):

Within 30 days of your last dose of study treatment, you will come in and meet with your study doctor and/or clinical study staff. At this visit, you will have a few procedures done which may include but not limited to a physical exam, check of the vital signs, check of your current medications and a blood draw.  
Following this visit, research staff will contact you every 6 months, until you complete 3 years of follow-up after you stop taking the study drug.
Clinical trial: NCT03287947
Section: Participant Responsibilities
Subsections: You Need To Tell Your Study Doctor Immediately If You Experience Any Side Effects While Taking Part In The Study.|Information On Birth Control (For Female Trial Participants)

Any medications (including over the counter and herbal supplements) that you are taking while taking nintedanib will be monitored by your study doctor or study staff. Some medications may affect the way nintedanib works. Please notify your study doctor or study staff immediately before you start taking any new medications.

As with any investigational drug, the effect of nintedanib on an unborn child is unknown. If you decide to take part in this trial and you are able to become pregnant, you must be willing to have a pregnancy test done before beginning your participation, and regularly at study visits and at the end of study treatment and beyond for at least 3 months after the last dose of nintedanib. Furthermore, you must avoid becoming pregnant while you take part in this trial. You cannot participate in this trial if you are pregnant, breastfeeding or plan to become pregnant during your trial participation.  
You must use a highly effective method of birth control. Some of the acceptable methods of contraception are listed below:
- an oral contraceptive (birth control pills) - an implantable or injectable contraceptive - an intrauterine device/system (IUDs / IUSs)
- transdermal patch
- double barrier method (two methods used at the same time) - bilateral tubal occlusion - vasectomized sexual partner (with appropriate post-vasectomy documentation of the absence of sperm in the ejaculate and provided that partner is the sole sexual partner of the participant
- complete sexual abstinence when this is in line with the preferred and usual lifestyle of the study participant. When there is complete sexual abstinence, the patient refrains from any sort of sexual activity that could involve the spill of an ejaculate, even if the spill does not occur
Your doctor will talk to you about the best method of birth control for you.  
If you are pregnant or think you could be pregnant, it is important for you to tell your doctor or research staff immediately. If you become pregnant during the trial, you will be removed from the trial and your health and your baby's health will be monitored throughout your pregnancy. Even if you are no longer in the trial, you will be contacted after your baby is born to find out about the baby's health. For MALE Trial Participants During study participation and for 3 months after your last study drug dose you should not father a child or donate sperm.
Clinical trial: NCT03287947
Section: Participant's Rights
Subsections: Getting Answers To Your Questions About Your Rights As A Research Subject

This study has been reviewed by an Institutional Review Board (IRB). This Committee reviewed this study to help ensure that your rights and welfare are protected and that this study is carried out in an ethical manner.  
For questions about your rights as a research subject, contact:
- By **mail**:  
  
Please reference the following number when contacting the Study Subject Adviser: Pro00021617.
Clinical trial: NCT03287947
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Risks|What Are The Costs Of Taking Part In This Study?|What Happens If I Am Injured Because I Took Part In This Study?

You may have side effects while you are on this study. Everyone taking part in the study will be carefully watched for side effects, especially for your liver enzymes. However, doctors don't know all the side effects that may happen. Side effects can be mild or very serious. Your doctor may give you medicines to lessen side effects. In some cases, side effects can be serious in that they can be long lasting, may never go away, may result in hospitalization, or may result in death. The **very common** (occurring in more than 10% of patients treated with nintedanib) risks in adult patients are:
- diarrhea - nausea - vomiting
- increased liver function tests (blood tests that show that show that your liver is not working the way it should)
- tiredness
- decreased appetite
- pain- abdominal pain, muscle cramps, chest pain, back pain, tumor pain - skin problems such as: itching, rash, hair loss, dry skin, hand foot syndrome, nail disorder
- electrolyte imbalance (electrolytes are minerals in the blood)
- abnormal skin sensations - bleeding e.g. nose bleeding, coughing up small amounts of blood, rectal bleeding
- mouth ulceration The **common** (occurring in more than 1% and less than 10% of patients treated with nintedanib) risks in adult patients are:
- taste changes - constipation - fever - high blood pressure - decrease in weight - headache
- infections including those in the urine, chest and sinuses
- dry mouth
- flatulence (gas)
- dizziness  
- dehydration - insomnia - blood clots in vein (venous thromboembolism) or in arteries (arterial thromboembolism including myocardial infarct)
The **rare** (occurring in less than 1% of patients treated with nintedanib) risks in adult patients are:
- cough
- chills
- vertigo (a feeling that the room is spinning)
- low blood pressure
- eye disorders, such as eye dryness, eye redness, conjunctivitis, vison blurred
- allergic reaction to drug, like itching, rash
- skin swelling
- abnormal heart beats, fast or slow heart beats
- low blood sugar
- changes in kidney function
- perforation (holes in the bowels)
- bleeding into the brain
- low production of the thyroid hormone
- pancreatitis (swelling and inflammation of the pancreas)
- In a few patients, an increase of bilirubin and liver enzymes was observed. This was fully reversible and appeared to be associated with progression of the underlying cancer disease and concomitant development of liver metastases. Enzyme elevations generally returned to normal upon temporarily stopping treatment in the majority of patients, and usually did not happen again after continuation of treatment at a lower dose. Your liver enzyme levels will be monitored closely during the conduct of this study. Extra blood samples and ultrasound images may be taken in order to clarify the potential underlying reason for the increased liver enzymes. If the cause of liver function changes cannot be found, further tests may be performed. This may include taking additional blood samples for further analysis of safety parameters, the analysis of the types and amounts of hormones, and the presence of viruses. Please inform your study doctor if you notice yellowing of the skin or of the white part of your eyes, which are signs of an increased bilirubin level in your body.  
- Previous animal studies suggest that decreased immune function may also occur when being treated with nintedanib. These animal studies also suggested that nintedanib in combination with natural sunlight or artificial UV radiation may cause effects to the skin or the eye. However, so far, these adverse events have not been reported in clinical trials with humans.

You and/or your health plan/insurance will need to pay for all routine care procedures. You may have to pay for these costs if they are not covered by your insurance company. If you choose to take part in the study, you will receive the study treatment, nintedanib, at no charge to you. Medicines that are not part of the study treatment will not be provided or paid for by LCI. You will not receive payment for taking part in this study. For more information on clinical trials and insurance coverage, you can visit the National Cancer Institute's web site at http://cancer.gov/clinicaltrials/understanding/insurance-coverage You can print a copy of the "Clinical Trials and Insurance Coverage" information from this web site. Another way to get the information is to call and ask them to send you a free copy. You may wish to discuss coverage with your insurance company before agreeing to participate in this research study.

If you become ill or are hurt while you are in the study, you will get the medical care that you need right away. In the event that you are harmed as a result of your participation in this study, inform your doctor immediately so you can access medical treatment. You and/or your health plan will be charged for this treatment in the usual manner. The study will not pay for standard medical treatment. The drug manufacturing company (Boehringer Ingelheim) will not provide any compensation for injury that occurred during the course of this research trial with nintedanib.  
You still have the right to make a claim through the legal system even if you sign this form, accept medical care, or accept payment for medical expenses.
Clinical trial: NCT03287947
Section: Procedures
Subsections: How The Study Works Before You Begin The Study (Pre-Treatment/Screening/Prior To 1St Dose Of Study Drug):|Specimen Collection For The Purposes Of Research:|During The Study (Intervention):

In order to participate in this study, you will need to:
- Review, sign, and date this informed consent document and - Provide authorization for the release of your medical records for research purposes.  
In order to check if you are eligible to participate, the following will be done:
- Information will be collected from your medical record about your demographics (i.e. age, race, etc.), medical history, your current disease, any treatments received before, and any medications you are taking. All of your medical history (oncological and relevant nononcological) findings that occurred prior to your signing this document will be documented.  
- If you are a woman who can have children, a urine or blood pregnancy test will be done.  
The test results must be negative in order to be in the study. You must also not be breastfeeding to participate in the study.  
- Office visit to conduct a physical exam and collect your height, weight, and vital signs (like temperature, pulse rate, respiratory rate, blood pressure).  
- Review of medications and supplements that you are currently taking
- Collect about two tablespoons of blood for laboratory tests to check your blood counts and determine how well your kidneys, liver, and other organs function.  
- Urinalysis (examination of the urine)
- Scans of your chest, abdomen and pelvis will be done using an x-ray machine that uses a computer to take pictures or computerized tomography (CT) scan.

If you agree to participate in this study, blood and ascites fluid may be collected and stored for future research. Ascites is a kind of fluid that may accumulate in the stomach. If your symptoms indicate a removal of the fluid, a procedure called a paracentesis will take place in order to remove it. A portion of this fluid (at least about 2 teaspoons) will be collected and stored for future analysis. At the same time you have blood drawn for routine labs, we will draw 1 tube of blood (about 2 tablespoons) for future research. If the future analysis is not performed, your blood and/or ascites samples(s) will be destroyed.  
If you need to undergo repeated paracentesis, we would collect fluid each time for testing, and a portion of this will be stored. If you qualify for the study and agree to participate, you will be enrolled and we will make arrangements to supply you with the study drug. The first dose of study drug should be taken on the day of your enrollment visit on Cycle 1 Day 1.

During the treatment period, each 28 day period of time is considered a "cycle." The cycles are repeated every 28 days and you are expected to complete at least 2 cycles, unless a study treatment delay is needed due to side effects. You will be removed from this study if your disease worsens during or after these 2 months. After this period, you may continue to participate in the study **only** if your disease is stable (about the same) or you are responding to the study treatment. Study treatment will be given to you to take home. You will take two 100mg nintedanib capsules by mouth in the morning and two 100mg capsules in the evening (approximately every 12 hours) with food and a full glass of water (8 oz.). If side effects or complications from study treatment occur, your study doctor may tell you to temporarily stop taking the study drug or to adjust the dose. In addition to taking nintedanib twice daily, you must also do the following:
- Swallow the capsule whole. Capsules should not be broken or crushed. - Keep the capsules in their original bottle.  
- If you miss a dose, you should not replace the missed dose but proceed to the next scheduled dose when it is due.  
- If vomiting occurs after taking a dose, an extra dose should not be taken.  
- Do not take any new prescription or herbal medication without first speaking with your study doctor or the clinical study staff.  
You will meet with your study doctor and/or clinical study staff every four weeks on Day 1 of each cycle for as long as you are being treated on the study. During these visits, you will have a physical exam, ECOG performance status (we will ask you how you are doing in terms of your ability to take care of yourself, your daily and physical activities) and we will take some blood (about 2 tablespoons) for research purposes and to check your blood counts, kidney and liver function. We will also check your vital signs and weight and ask about any side effects you may have experienced. We may ask that you have additional office visits and/or laboratory testing if you have symptoms or side effects. In addition to the visits on Day 1 of each cycle as referenced above, we will ask you to have your blood pressure taken and report to the study team member during a phone call for the first three weeks of Cycles 1 and 2. You may have your blood pressure taken at home if you have a blood pressure machine or you may go to another clinic of your choice (i.e. local pharmacy) for a blood pressure reading. There are multiple drugs (prescription and over the counter medications and dietary/herbal supplements including what are sometimes called "complementary" or "alternative" medicines) that may interact with nintedanib. Your study doctor or study staff will review all of the medications and supplements you are currently taking before starting you on this investigational drug. You should not take any new medications or dietary supplements without discussing with your study doctor or study staff first. A CT scan of your chest, abdomen, and pelvis (or acceptable alternative testing) will be planned at the completion of cycle 2 of receiving the study drug. You will continue to receive the study drug until your cancer gets worse, until side effects become unbearable even if they are being medically treated, or until you are too ill to continue. You also have the option to voluntarily discontinue study treatment and withdraw from the study at any time. If neither of the above mentioned scenario happens and you continue to receive the study drug, a CT scan (or acceptable alternative testing) will be necessary at the completion of every 2 cycles (e.g. cycles 4, 6, 8). In order to document the current status of your disease (which could be a response, stable disease, or progressive disease) we will make all efforts to obtain scans and assess your tumor every 8 weeks
(+/- 2 weeks). If you decide to discontinue therapy, every effort will be made to obtain any future scan results unless your disease worsens or you start new treatment. Your study doctor may also choose to withdraw you from the study for any reason, including if you are unable to adhere to the study schedules and requirements.
Clinical trial: NCT03287947
Section: Purpose of Research
Subsections: Why Is This Study Being Done?

Cancer of the appendix is a rare disease, so there is limited data regarding its treatment. The study drug, nintedanib, is approved by the U.S. Food and Drug Administration (FDA) for treating a medical condition called an idiopathic pulmonary fibrosis, a progressive condition which may lead to death. Nintedanib has shown antitumor activity in clinical trials of lung and ovarian cancer, and has been studied in advanced colorectal cancer; however, nintedanib is not currently FDA approved for the treatment of appendix cancer. Given the similarities between appendiceal and colorectal cancer, and potentially ovarian cancer, and the limited information about the best way of treating metastatic appendiceal carcinomas, further investigation with nintedanib is needed.
Clinical trial: NCT03287947
Section: Withdrawal from Study
Subsections: What If I Want To Quit The Study Later On?

Your participation in this study is completely voluntary. You should feel under no pressure to be in the study. If you decide not to be in the study, that will not in any way harm your relations with your doctors or with Carolinas HealthCare System. You are free to stop being in the study if you change your mind after entering it. This would not harm your relations with your doctors or Carolinas HealthCare System. Information contributed to the study will remain in the study even if you choose to withdraw. If you choose to withdraw from the study, please notify the study doctor in writing at the address on page 1 of this consent form. Your study doctor may choose to involuntarily withdraw you from the study for any reason, including if you are unable to adhere to the study schedule or requirements. We will tell you about new medical findings that may affect your willingness to continue in the study.