Clinical trial: NCT01683994
Section: Alternatives
Subsections: What Other Choices Do I Have If I Do Not Take Part In This Study?

Instead of being in this study, you have these options:
- Getting treatment or care for your cancer without being in a 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. It does not treat the cancer directly. Instead, it tries to improve how you feel. Comfort care tries to keep you as active and comfortable as possible.  
Please talk to your doctor about these and other options.
Clinical trial: NCT01683994
Section: Confidentiality
Subsections: Will My Medical Information Be Kept Private?

Your privacy is very important to us and we will make every effort to protect it. Your information may be given out if required by law. However we will do our best to make sure that any information that is released will not identify you. There are organizations that may inspect your records. These organizations are required to make sure your information is kept private. Some of these organizations are:
- The study sponsor
- The Food and Drug Administration (FDA)
- The drug company supporting the study. - The local Institutional Review Board, IRB, is a group of people who review the research with the goal of protecting the people who participate in the study.
A description of this clinical trial will be available on http://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 study results. You can search this Web site at any time.
Clinical trial: NCT01683994
Section: Participant Responsibilities
Subsections: At Each Study Visit, We Ask That You Bring All Remaining Cabozantinib Tablets With You.|We Ask That You:

During Phase I of the study, 3 - 6 people will be enrolled and will take a 20 mg dose of cabozantinib once each day of each 21 day cycle. This is dose level 1. Based on how people tolerate the medication, the dose may be reduced for the next group of people enrolled or it may be increased. We will continue to enroll people until we find the highest dose that 6 people can take with only 0 or 1 experiencing intolerable side effects. We will then enroll 6 additional people to the study at that dose to obtain additional safety information about the combination therapy and to begin to find out how well the combination therapy works.  
In a second phase of the study we will enroll some patients who will be assigned to receive docetaxel only and some patients who will receive docetaxel and cabozantinib together. Patients will be randomly assigned (like flipping a coin) to receive one of the two regimens. You will have an equal chance of being assigned to one of the two regimens. Unless you experience serious side-effects or your disease progresses (gets worse), there is no limit to the number of cycles you may remain on the study regimen. Therapy may be stopped, however, for any of the reasons listed in the stopping therapy section below.

- avoid eating or drinking grapefruit and grapefruit products including grapefruit juice as well as Seville oranges and their products while enrolled on study as this may adversely interact with cabozantinib. Please read the product label as some products may contain grapefruit without your knowledge.  
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**  
NIH-2514-1 (07-09)  
NIH-2514-2 (10-84) P.A.: 09-25-0099 File in Section 4: Protocol Consent  
STUDY NUMBER: 12-C-0204 CONTINUATION: page 5 of 14 pages
- **discuss any planned dental procedures with the study team if you are taking or have**
taken in the past a type of drug called a bisphosphonate (e.g. alendronate, risedronate, pamidronate, etc.). Patients taking bisphosphonates and cabozantinib are at higher risk for a complication that may lead to the destruction or death of the jawbone.  
You may take antacids and other medications used to treat indigestion with the exception of cimetidine. Please let the study staff know, if you have been taking cimetidine. You may take an alternative medication for the duration of the study. Please discuss these options with the study doctor.
Clinical trial: NCT01683994
Section: Participant's Rights
Subsections: Research Subject'S Rights What Are The Costs Of Taking Part In This Study?

If you choose to take part in the study, the following will apply, in keeping with the NIH policy:
- The study agents, cabozantinib, docetaxel and prednisone will be provided by the NCI. You will receive study treatment at no charge to you. This may include surgery, medicines, laboratory testing, x-rays or scans done at the Clinical Center, National Institutes of Health (NIH), or arranged for you by the research team to be done outside the Clinical Center, NIH if the study related treatment is not available at the NIH.  
- There are limited funds available to cover the cost of some tests and procedures performed outside the Clinical Center, NIH. You may have to pay for these costs if they are not covered by your insurance company.  
- Medicines that are not part of the study treatment will not be provided or paid for by the Clinical Center, NIH.  
- Once you have completed taking part in the study, medical care will no longer be provided by the Clinical Center, NIH.
Clinical trial: NCT01683994
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Risks Or Discomforts Of Participation|Rare, And Serious In 100 People Receiving Xl184, 3 Or Fewer May Have:|Occasional, Some May Be Serious|Occasional, Some May Be Serious|Rare, And Serious|Prednisone Common, Some May Be Serious|Occasional, Some May Be Serious|Occasional, Some May Be Serious|Potential Benefits Of Participation Are There Benefits To Taking Part In This Study?

What side effects or risks can I expect from being in this study?  
If you choose to take part in this study, there is a risk that:
- You may lose time at work or home and spend more time in the hospital or doctor's office than usual
- You may be asked sensitive or private questions which you normally do not discuss
The medications used in this study may affect how different parts of your body work such as your liver, kidneys, heart, and blood. The study doctor will be testing your blood and will let you know if changes occur that may affect your health. The docetaxel which is used in this study also contains ethanol or alcohol which may cause you to feel drunk during or after treatment. It STUDY NUMBER: 12-C-0204 CONTINUATION: page 7 of 14 pages may be necessary to avoid driving, operating any machinery or performing any activities that are dangerous for one to two hours after the infusion of docetaxel. Some medications such as pain relievers or sleep aids may interact with the alcohol in docetaxel and may worsen these effects. There is also a risk that you could have side effects from the study drug(s)/study approach.  
Here are important points about side effects:
- The study doctors do not know who will or will not have side effects.  
- Some side effects may go away soon, some may last a long time, or some may never go away.  
- Some side effects may interfere with your ability to have children.  
- Some side effects may be serious and may even result in death.
Here are important points about how you and the study doctor can make side effects less of a problem:
- Tell the study doctor if you notice or feel anything different so they can see if you are having a side effect.  
- The study doctor may be able to treat some side effects.  
- The study doctor may adjust the study drugs to try to reduce side effects.  
The tables below show the most common and the most serious side effects that researchers know about. There might be other side effects that researchers do not yet know about. If important new side effects are found, the study doctor will discuss these with you.

- A tear or hole in internal organs that may require surgery
- Non-healing surgical site
- Damage to the jawbone which may cause loss of teeth
- Brain damage which may cause headache, seizure, blindness (also known as Reversible Posterior Leukoencephalopathy Syndrome)  
  
STUDY NUMBER: 12-C-0204 CONTINUATION: page 9 of 14 pages

In 100 people receiving Docetaxel, from 4 to 20 may have:
- Severe skin rash with blisters and peeling which can involve inside of mouth and other parts of the body
- Belly pain
- Bruising, bleeding
- Liver damage which may cause yellowing of eyes and skin
- Kidney damage which may require dialysis
- Blood clot which may cause swelling, pain, shortness of breath
- Abnormal heart rate
- Shortness of breath, wheezing
- Chest pain

In 100 people receiving Prednisone, from 4 to 20 may have:
- Cloudiness of the eye, visual disturbances
- Glaucoma
- Infection
- Non-healing wound
- Diabetes
- Damage to the bone which may cause joint pain and loss of motion
- Kidney stones
- Heartburn RARE, **AND SERIOUS**
In 100 people receiving Prednisone, 3 or fewer may have:
- Bleeding from sores in the stomach
- Broken bones

In 100 people receiving Docetaxel, 3 or fewer may have:
- Allergic reaction which may cause rash, low blood pressure, wheezing, shortness of breath, swelling of the face or throat
- Cancer of bone marrow (leukemia) caused by chemotherapy - Scarring of the lungs STUDY NUMBER: 12-C-0204 CONTINUATION: page 10 of 14 pages

In 100 people receiving Prednisone, more than 20 and up to 100 may have:
- In children and adolescents: decreased height
- Loss of bone tissue
- Mood swings - Skin changes, acne
- Swelling of the body, tiredness, bruising
- High blood pressure which may cause headaches, dizziness, blurred vision
- Pain in belly
- Increased appetite and weight gain
- Weight gain in the belly, face, back and shoulders

In 100 people receiving Docetaxel, from 4 to 20 may have:
- Severe skin rash with blisters and peeling which can involve inside of mouth and other parts of the body
- Belly pain
- Bruising, bleeding
- Liver damage which may cause yellowing of eyes and skin
- Kidney damage which may require dialysis
- Blood clot which may cause swelling, pain, shortness of breath
- Abnormal heart rate
- Shortness of breath, wheezing
- Chest pain

In 100 people receiving Prednisone, from 4 to 20 may have:
- Cloudiness of the eye, visual disturbances
- Glaucoma
- Infection
- Non-healing wound
- Diabetes
- Damage to the bone which may cause joint pain and loss of motion
- Kidney stones
- Heartburn RARE, **AND SERIOUS**
In 100 people receiving Prednisone, 3 or fewer may have:
- Bleeding from sores in the stomach
- Broken bones

We do not know if you will receive personal, medical benefit from taking part in this study. These potential benefits could include shrinking of your tumor or lessening of your symptoms, such as pain, that are caused by the cancer. Because there is not much information about the drug's effect on your cancer, we do not know if you will benefit from taking part in this study, although the knowledge gained from this study may help others in the future who have cancer.  
STUDY NUMBER: 12-C-0204 CONTINUATION: page 11 of 14 pages
Clinical trial: NCT01683994
Section: Procedures
Subsections: Before You Begin The Study:|During The Study:

You will need to have the following exams, tests or procedures to find out if you can be in 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. However, there are some extra exams, tests and procedures that you will need to have if you take part in this study. If you have had some of them recently, they may not need to be repeated. These tests include:
- 12-lead electrocardiogram (ECG)  
- Blood and urine tests
- CT scan (chest, abdomen and pelvis) and a bone scan You will need to supply a complete list of your current medications to the study doctor. This includes over-the-counter medications and herbal supplements. Some medications may interact adversely with cabozantinib and it is important that your study doctor and prescribing physician be aware of any potential risks so that they can prescribe alternative medications as necessary. If you do not already do so, please consider carrying a list of your medications at all times.  
STUDY NUMBER: 12-C-0204 CONTINUATION: page 3 of 14 pages

If the results show that you can be in the study, and you choose to take part, then you will need the following tests and procedures:  
- Dental examination (if you have used or are using a type of medication called a  
  
bisphosphonate ) - before you receive study drug
You will need the following tests and procedures that are part of regular cancer care.  
These tests will be done day 1 of each cycle.  
- Blood tests
- Examination by a doctor These tests will be done on day 1 of each cycle
- Urine tests
- ECG
You will also need these tests and procedures that are part of regular cancer care. They are being done more often because you are in this study.  
- Bone scan and CT scan every 3 cycles You will need blood and urine tests for research to see how the drug is affecting your body and for other research studies. These tests will be done:  
- After you have enrolled but before you receive any study drug
- Before you receive the study drug on the following days: Day 1 of cycles 1, 2, 3, and 5
- After you receive the study drug at seven timepoints up to 24 hours after the first dose on day 1 on cycles 1 and 2, if you are enrolled to phase I or assigned to receive cabozantinib during phase II
You will be provided with a wallet-sized information card ("Information on Possible Drug Interactions") that names your study agent and outlines the specific risk of adverse interactions with other drugs or substances. Should you require any new medications while on study, please consult with your study doctor if possible, and present the card to the prescriber (doctor, pharmacist, physician's assistant, or nurse practitioner). Please check with your doctor/prescriber or pharmacist before using any new over-the-counter medications or herbal supplements. You will need to be admitted to the hospital for the first 2 days of cycle 1 and 2 so that we may collect blood samples from you. After that, you will receive the medications in this study as an outpatient.  
STUDY NUMBER: 12-C-0204 CONTINUATION: page 4 of 14 pages You will be given docetaxel through an IV catheter (a plastic tube usually inserted in a vein on your arm) on day 1 of each cycle. Each docetaxel infusion will take about 1 hour. You will also be asked to take prednisone by mouth twice each day of each 21 day cycle. You should take prednisone at around the same time every day with the doses approximately 12 hours apart, give or take two hours. Prednisone should, if possible, be taken with food or milk to reduce stomach irritation. If you vomit or miss a dose of prednisone, that is, if more than 14 hours have passed since the previous dose, you should not make up that dose. Instead, you should resume taking the drug at the next scheduled dose. You will also take an assigned dose of cabozantinib by mouth in combination with the agents described above. The study team will tell you when you should take this dose. Cabozantinib should be taken on an empty stomach (no food should be eaten 2 hours before taking cabozantinib and1 hour after taking cabozantinib) and the pills should not be chewed or crushed. If you miss a dose or vomit, do not make up that dose even if you think you saw it come out. Instead, you should resume taking the drug at the next scheduled dose. In Phase I of the study, you will be given docetaxel in combination with cabozantinib. If you are enrolled to Phase II of the study, you may or may not receive cabozantinib.
Clinical trial: NCT01683994
Section: Purpose of Research
Subsections: Why Is This Study Being Done?

Cabozantinib is an agent that slows down the growth of blood vessels that feed tumors. Although it has been approved by the Food and Drug Administration to treat medullary thyroid cancer, it has not been approved for prostate cancer and its use in this study is experimental. Early studies have also shown that prostate tumors respond to cabozantinib. However when cabozantinib was taken alone, it did not shrink prostate tumors better than standard FDA approved therapies. In this study we will be investigating how cabozantinib works in combination with the FDA approved standard chemotherapy regimen of docetaxel and prednisone in people who have been diagnosed with metastatic (distantly spread) prostate cancer.  
PATIENT IDENTIFICATION **CONSENT TO PARTICIPATE IN A CLINICAL**  
RESEARCH STUDY - Adult Patient or - Parent, for Minor Patient  
NIH-2514-1 (07-09) P.A.: 09-25-0099  
File in Section 4: Protocol Consent (1)  
STUDY NUMBER: 12-C-0204 CONTINUATION: page 2 of 14 pages First we will try to establish safe doses for these drugs when they are taken together. We also hope to understand whether cabozantinib given together with docetaxel works better to treat distantly spread prostate cancer than when docetaxel is given alone.
Clinical trial: NCT01683994
Section: Withdrawal from Study
Subsections: When You Are Finished **Taking The Study Drugs (Treatment)**|Stopping Therapy

After you have taken your last dose of cabozantinib, we will conduct an end of study assessment. At this time, you will have a brief examination, your blood and urine will be tested and you will have an ECG. This assessment can be done any time within 30 days after you have completed treatment. After you finish study treatment, your local doctor will provide your cancer care.

Your participation in this study will continue until either you or your study team decides that this medication is not beneficial to you. Your participation is voluntary; so you may stop receiving the study drugs at any time, but we ask that you speak to your study team before stopping. Your doctor may decide to stop your therapy for the following reasons:
- if he/she believes that it is in your best interest  
- if your disease progresses during treatment
- if you have side effects from the treatment that your doctor thinks are too severe
- if new information shows that another treatment would be better for you
- if you are unable to comply with the protocol requirements
- if you are unable to tolerate the lowest dose of cabozantinib (20 mg once every other day) - if your treatment has been delayed for more than 2 weeks and it is not clear that you have been benefiting from cabozantinib
In this case, you will be informed of the reason therapy is being stopped. If you decide at any time to withdraw your consent to participate in the trial, we will not collect any additional medical information about you. However, according to FDA guidelines, information collected on you up to that point may still be provided to Exelixis or designated representatives. If you withdraw your consent and leave the trial, any samples of yours that have been obtained for the study and stored at the NCI can be destroyed upon request. However, any samples and data generated from the samples that have already been distributed to other researchers or placed in the research databases cannot be recalled and destroyed.  
STUDY NUMBER: 12-C-0204 CONTINUATION: page 6 of 14 pages Birth Control Because the effects of cabozantinib in combination with docetaxel and prednisone on the developing human fetus are unknown, men participating in this study must agree to practice an effective form of birth control before starting study treatment, during study treatment, and for 4 months after you finish study treatment. If you think that your partner is pregnant, you should tell your study doctor or nurse at once.  
Effective forms of birth control include:
- abstinence - intrauterine device (IUD) - hormonal [birth control pills, injections, or implants]
- tubal ligation
- vasectomy
You should recognize that no method of birth control besides abstinence provides 100% protection from pregnancy.