Clinical trial: NCT02139397
Section: Alternatives
Subsections: 40 What Are The Benefits Of Participating In The Study?|48 What Other Options Are There?

41 42 Taking part in this study may or may not make your health better. While benefit is 43 possible, participation may not benefit you and your health could worsen during this study.  
44 45 We do know that the information from this study will help doctors learn more about DFMO
46 as a treatment for cancer. This information could help future cancer patients.  
47

1 2 Your other choices may include:
3 4 - Getting treatment or care for your cancer without being in a study 5 - Taking part in another study 6 - Getting no specific treatment 7 - You can receive bortezomib off-study without receiving DFMO
8 9 You should talk to your home treating oncologist about your choices before you decide if 10 you will take part in this study.  
11
Clinical trial: NCT02139397
Section: Confidentiality
Subsections: 4 **What Will Be Done With My Information?**|12 **Why Am I Being Asked To Give Permission For The Use And Disclosure Of**|21 **What Information Will Be Used And Shared For This Study?**|30 With Whom Will My Information **Be Shared (Disclosed)?**|9 **Can I Stop My Protected Health Information From Being Collected And**|21 What Happens If I Do Not Want You To Use And Share **My Health**|27 **When Will My Information Be Destroyed?**

5 Each subject in this trial will be identified by a unique identifier that will be used on all 6 report forms and any other material submitted to the NMTRC. Report Forms for this study 7 will be both paper and electronic. Electronic data will be stored in a secure data center.  
8 Your health information will be collected and entered in this password-secure database 9 along with the information from other people taking part in this study, and will only be 10 accessible to the people involved in conducting this research.  
11

13 *my information?*
14 Your health information will be used to evaluate the safety and tolerability of the study 15 drug, DFMO, in combination with another drug (bortezomib) as well as your tumor's 16 response to the study drug.  
17 18 To evaluate the study drug and your response, we need to see and use your health 19 information.  
20

22 To complete this research study, we will need to collect and share (disclose) information 23 about you. This information may include:
24 - Your date of birth, name, contact information, medical record number, and 25 insurance information.  
26 - Existing medical records and medical history. 27 - New health information collected for purposes of this study. 28 - Copies of medical records you have with other health care providers.  
29

31 - The Sponsor(s) of the research or its agents (monitors, auditors): Dr. Giselle 32 Sholler, the Neuroblastoma and Medulloblastoma Translational Research 33 Consortium (NMTRC), affiliates of the NMTRC, and the NMTRC010B study 34 committee 35 - The study doctor and his/her research staff 36 - Spectrum Health Hospitals staff or its agents 37 - KC Pharma (the maker of the study drug) 38 - The Western Institutional Review Board® (WIRB®)
39 - The Spectrum Health Institutional Review Board (IRB) and its staff 40 - The Food and Drug Administration (FDA) and other government agencies who 41 regulate this study 42 43 Once your protected health information has been shared (disclosed), it is possible that 44 anyone who receives that information may re-disclose it. Because some of these 45 individuals who receive your protected health information may not be required by law to 46 keep your information confidential, we cannot guarantee that your information will not be 1 released or made available to another party once it leaves your treating institution. 2 Therefore, we share your information only if necessary and we use all reasonable efforts 3 to request that those individuals who receive your information take steps to protect your 4 privacy.  
5

10 *shared?*
11 You can tell us to stop collecting your health information at any time. We will stop using 12 and sharing your information, except in very limited cases if needed to comply with law, 13 protect your safety, or make sure the research was done properly. If you have any 14 questions about this please ask.  
15 16 If you want us to stop using and sharing your health information, you must tell us in writing.  
17 Send your written request to:
18 19 [insert study doctor contact information]
20

22 *information?*
23 If you decide not to give permission for us to use and share your health information, you 24 will not be able to participate in this study. Your decision will in no way affect your medical 25 care or cause you to lose any benefits to which you are entitled.  
26

28 We do not know when your information will no longer be used. Unless you tell us to stop 29 using and sharing your information, it will be kept for an indefinite length of time.  
30 31 **[If the HIPAA authorization form will be a document separate from the consent**
32 **form, appropriate signatures blocks need to be inserted here].**
33 34 **ADDITIONAL OPTIONAL TUMOR BIOLOGY CONSENT**
35 36 There are optional biology tests that you may agree to participate in if you wish. These 37 include urine and blood samples, extra bone marrow samples, and extra tumor samples. 38 These samples may be collected during routine procedures while you are in the study, 39 and will be used for research tests and studies that will not directly impact your treatment.  
40 These research tests and studies may benefit future children with neuroblastoma or other 41 tumors.  
42 43 If you agree to allow your samples to be used for these future research tests, your 44 samples will be stored in a safe and confidential laboratory area indefinitely. Neither your 45 name nor any other information that identifies you will be used to identify your sample 1 when they are stored in the lab. The samples will be identified only by a unique, de-2 identified code. Samples will be frozen and stored in a carefully controlled deep freezer.  
3 The samples that are stored for future research may only be used by Dr. Sholler and the 4 other investigators who are participating in this study or other NMTRC studies. No 5 information that identifies you will be used for any of these future research tests and 6 studies.  
7 8 You have the option to remove the samples from the laboratory at any time. In the future, 9 if you ask that your stored samples be destroyed, it is important to know that any research 10 that has already been done on the samples cannot be changed. No matter what you 11 decide to do, it will not affect the care that you will get.  
12 13 There is no way to predict exactly what research tests will be performed with the stored 14 samples. Because these tests are for research only, usually your study doctor or you 15 will not know the results. It is very unlikely that the research testing might find important 16 information about your current or future health. If this unlikely event happens, the 17 researchers may contact your primary treating oncologist about what the research test 18 results might mean. Only your primary treating oncologist will be notified and the 19 information will not become part of your medical record. Your primary treating oncologist 20 may discuss this unexpected finding with you, and may recommend that you see a 21 genetic counselor and/or repeat testing in a clinical (not research) laboratory if needed. 22 It is possible that your primary treating oncologist may decide that no action is needed.  
23 24 Future research tests will be looking at genetic information collected from the samples 25 you provide. A Federal law, called the Genetic Information Nondiscrimination Act 26 (GINA), generally makes it illegal for health insurance companies, group health plans, 27 and most employers to discriminate against you based on your genetic information. This 28 law generally will protect you in the following ways: Health insurance companies and 29 group health plans may not request your genetic information that we get from this 30 research. Health insurance companies and group health plans may not use your genetic 31 information when making decisions regarding your eligibility or premiums. Employers 32 with 15 or more employees may not use your genetic information that we get from this 33 research when making a decision to hire, promote, or fire you or when setting the terms 34 of your employment.  
35 36 GINA does not protect you against genetic discrimination by companies that sell life 37 insurance, disability insurance, or long-term care insurance. GINA does not prohibit 38 discrimination on the basis of an already manifest genetic disease or disorder.  
39 40 1. I agree that additional urine samples may be taken and sent to a laboratory working 41 with the NMTRC for additional tests.  
42  
  
45 46 2. I agree that additional blood samples may be taken and sent to a laboratory 47 working with the NMTRC for additional tests.  
48  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
1 \#2: Yes_____ No_____ ________ / _______  
  
  
  
 2 Initials Date 3 4 3. I agree that additional blood samples may be taken and sent to an NMTRC
5 laboratory for biological correlates and additional studies.  
6 7 \#3: Yes_____ No_____ ________ / _______ 8 Initials Date 9 10 4. I agree that extra bone marrow may be taken and sent to an NMTRC laboratory 11 for additional studies.  
12 13 \#4: Yes_____ No_____ ________ / _______
14 Initials Date 15 16 5. If I have a standard of care tumor extraction, extra tumor samples may be taken 17 and sent to an NMTRC laboratory for additional studies.  
18 19 \#5: Yes_____ No_____ ________ / _______
20 Initials Date 21 22 6. I agree to let researchers store material (e.g., leftover urine, blood, cells or genetic 23 material that is taken at the time of a procedure) for future use to learn about, 24 prevent, or treat cancer.  
25 26 \#6: Yes_____ No_____ ________ / _______
27 Initials Date 28 29
Clinical trial: NCT02139397
Section: Duration of Study Involvement
Subsections: 44 How Many People Will Take Part In The Study?

45 46 In this study, approximately 38 to 62 subjects will participate from about 15 medical 47 centers across the United States. Approximately 5 of these subjects will be at the 48 [INSERT INSTITUTION NAME HERE].  
1
Clinical trial: NCT02139397
Section: Participant's Rights
Subsections: 11 **Consent And Assent Instructions:**

12 Consent: *Subjects 18 years and older must sign on the subject line below* 13 *For subjects under 18, consent is provided by the parent or guardian* 14 Assent: Is not required for subjects 12 *years and younger* 15 Verbal assent is required for subjects ages 13 *through 17 years using the* 16 *Assent section below* 17 18 19 20 Signature of Subject (18 years and older) Date 21 22 23 24 Name of Subject Printed 25 26 27 28 Signature of Parent or Guardian Date 29 (applicable for children)
30 31 (*If available)*
32 33 34 35 Name of Parent or Guardian Printed 36 37 38 39 Signature of Parent or Guardian Date 40 (applicable for children)
41 42 43 44 Name of Parent or Guardian Printed 45 46 **ASSENT SECTION:**
47 Statement of person conducting assent discussion:
48  
1 - I have explained all aspects of the research to the subject to the best of his or 2 her ability to understand.  
3 - I have answered all the questions of the subject relating to this research.  
4 - The subject agrees to be in the research.  
5 - I believe the subject's decision to enroll is voluntary. 6 - The study doctor and study staff agree to respect the subject's physical or 7 emotional dissent at any time during this research when that dissent pertains 8 to anything being done solely for the purpose of this research.  
9 10 11 12 Signature of Person Conducting Assent Discussion Date 13 14 Statement of Parent or Guardian:
15 16 My child appears to understand the research to the best of his or her ability and 17 has agreed to participate.  
18 19 20 21 Signature of Parent or Guardian Date 22 23 ---------------------------- **Use this witness section only if applicable -------------------------**
24 25 *If this consent form is read to the subject because the subject or the subject's parent or* 26 *guardian is unable to read the form, an impartial witness not affiliated with the research* 27 *or investigator must be present for the consent and sign the following statement:*
28 29 I confirm that the information in the consent form and any other written information was 30 accurately explained to, and apparently understood by, the subject or the subject's 31 parent or guardian. The subject or the subject's parent or guardian freely consented to 32 be in the research study.  
33 34 35 36 Signature of Impartial Witness Date 37 38 Note: This signature block cannot be used for translations into another language. A 39 translated consent form is necessary for enrolling subjects who do not speak English.  
40 41 **HIPAA AUTHORIZATION FORM FOR USE & DISCLOSURE OF HEALTH**
42 INFORMATION FOR RESEARCH PURPOSES **(TEMPLATE)**
43 44 The information we are asking to use and disclose (share) for this research study may 45 include your Protected Health Information (PHI). This information is protected by a 46 federal law called the Health Insurance Portability and Accountability Act (HIPAA). In
1 general, we cannot use or share your health information for research without your 2 permission.  
3
Clinical trial: NCT02139397
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: 9 **What Are The Risks And Discomforts Of The Study?**|18 Risks Of Blood Draws:|26 Risks Of Bone Marrow Aspiration:|5 Reproductive Risks:

10 11 You may have side effects while on the study. Everyone taking part in the study will be 12 carefully watched for any side effects. However, study doctors do not know all the side 13 effects that may happen. Side effects may be mild or very serious. Your health care team 14 may give you medicines to help lessen side effects. Many side effects go away soon 15 after you stop taking the study drug. In some cases, side effects can be serious, long 16 lasting, may never go away, or may even cause death. You should talk to your study 17 doctor about any side effects that you have while taking part in the study.  
18 19 **Risks of DFMO:**
20 21 The risks of DFMO are not completely known in the pediatric population. That is one 22 reason that this study is being done.  
23

19 20 Risks associated with drawing blood are slight, but some risks include: pain, excessive 21 bleeding, fainting or feeling lightheaded, bruising, infection (a slight risk any time the skin 22 is broken), and multiple punctures to locate veins.  
23 24 Blood will be drawn from a central line whenever possible to minimize these risks.  
25

27 28 During this study, a sample of bone marrow will be collected from your hip bone(s) for 29 testing (occasionally another bone is selected); this is usually done under anesthesia.  
30 Once you are under the anesthesia, a special needle will be inserted into the bone to 31 collect the marrow. Pressure may be felt as the needle is inserted into the bone. There 32 is a sharp sucking sensation as the marrow is aspirated, which lasts for only a few 1 moments. There may be some bleeding at the puncture site. You may experience 2 discomfort or pain. More serious risks, such as serious bleeding or infection, are very 3 rare.  
4

6 7 DFMO was damaging to developing embryos in animal studies. Because the effects of 8 DFMO on an unborn child or nursing infant are not known you may not take part in this 9 study if you are pregnant or breastfeeding. Girls who can become pregnant (age 13 or 10 older or have started having menses) who enter the study must have a negative 11 pregnancy test prior to entry and during the study. Additionally, the effects of DFMO on 12 sperm are not known. If you are a girl who can become pregnant or a male able to father 13 children, you must use an acceptable method of birth control during the study to prevent 14 pregnancy.  
15 16 Both men and women should use one of the more effective birth control methods during 17 treatment and for six months after treatment is stopped. These methods include 18 19 - total abstinence (no sex),
20 - oral contraceptives ("the pill"),
21 - an intrauterine device (IUD), 22 - levonorgestrol implants (Norplant), or 23 - medroxyprogesterone acetate injections (Depo-provera shots).  
24 25 If one of these cannot be used, contraceptive foam with a condom is recommended. Talk 26 to your study doctor to decide what type of birth control is acceptable.  
27 28 A possible effect of this study is the possibility of sterility (inability to have children).  
29 30 If you suspect that you have become pregnant during this study, you must notify the 31 research team immediately. You will be withdrawn from the study if you become pregnant.  
32 33 For more information about risks and side effects, ask your study doctor.  
34 35 You will be informed as additional information is discovered about how the study drug 36 may affect the risk and/or your willingness to continue to participate in this study. Your 37 study doctor will inform you of all known risks; however, there may be physical, mental or 38 genetic adverse risks that are not known at this time.  
39
Clinical trial: NCT02139397
Section: Procedures
Subsections: 2 What Is Involved In The Study?|14 Tests To Be Performed Within 5 Days Of Starting Study:|22 Tests To Be Performed Within 21 Days Of Starting Study:|37 Tests To Be Performed For Research Related Purposes Only Include: 38 - Audiogram; A Hearing Test That Can Detect Hearing Loss That Is Not Noticed In|27 **Methods For Providing/Administering Study Drug**

3 4 Screening:
5 You will undergo a number of standard tests and research-related procedures before 6 being able to enroll in this study. You will need to have the following exams, tests and 7 procedures to find out if you can be in the study. The results of these studies may 8 show that you are not eligible to take part in this study. Most of these exams, tests 9 and procedures are part of regular neuroblastoma care and may be done even if you 10 do not join the study. Some procedures are being done only for research purposes as 11 part of this study. Those tests are also listed below. If you have had some of them 12 recently, they may not need to be repeated. This will be up to your study doctor.  
13

15 - Medical history 16 - Physical exam 17 - Vital signs (blood pressure, pulse, temperature) 18 - Blood tests 19 - Urine tests (including a pregnancy test for girls who can become pregnant {age 20 13 or greater, or has started menstruation})
21

23 - MRI or CT scan of the tumor(s) 24 - Any other imaging studies or tests deemed necessary for assessing your tumor 25 by your treating physician 26 - MIBG or PET scan. An MIBG scan involves injecting a radioisotope into the 27 blood on the first day, and then scanning the whole body on the second day to 28 see where the isotope was absorbed.  
29 - Bone marrow aspirations and examination (this involves using a needle to 30 extract a small amount of your bone marrow from both of your hips usually 31 under anesthesia; at the time of your procedure you will be asked to sign a 32 consent form for the anesthesia). We will ask you if we can collect a small 33 amount of additional bone marrow that will be used for special research testing 34 of neuroblastoma cells if they are present. (There is a separate consent for this 35 at the end of this form.)
36

39 daily conversation 40 - Urine samples (additional samples are voluntary) 41 - Additional samples of your Bone marrow aspirations as noted above (additional 42 samples are voluntary)
43 - Additional samples of your blood (additional samples are voluntary)
44 45 As part of this study you will have an audiogram (hearing test) performed before you 46 start taking the study drug and again at the end of cycles 2, 6, and then yearly. An 1 audiogram may also be requested by the study doctor at any time to check for changes 2 in your hearing.  
3 4 **Study Treatment:**
5 If the exams, tests and procedures show that you can be in the study, and you choose 6 to take part, DFMO and bortezomib will be started in clinic on Day 1. You will take 7 DFMO orally, by mouth, twice a day. DFMO will be provided to you as a tablet. If you 8 are unable to swallow tablets you will need to crush them and mix with water or other 9 liquid to then drink. Bortezomib will be given to you intravenously (IV).  
10 11 You will be in clinic on this first day for approximately 3 to 5 hours. After this, you will 12 be given the DFMO to take home and you will take it each day as prescribed for as 13 long as you are in this study, unless you have side effects from the medicine or your 14 tumor worsens. You will return to clinic on days 4 and 8 to receive bortezomib again, 15 and will also return to clinic on day 15 for a physical exam during every cycle while in 16 this study. These visits will last about 2 hours.  
17 18 DFMO and bortezomib will be given to you in six individual cycles (courses) of therapy. 19 Each course of therapy lasts 21 days; this is what we call a "cycle". Each cycle will 20 occur immediately after the last. This means that since each cycle is 21 days long, 21 on day 22 you will be starting the next cycle.  
22 23 At the beginning of each new cycle you will have some of these tests repeated 24 including:
25 - Medical history 26 - Physical exam 27 - Vital signs (blood pressure, pulse, temperature)
28 - Blood tests 29 - Urine tests (including a pregnancy test for girls who can become pregnant) 30 - Any other imaging studies or tests deemed necessary for assessing your tumor 31 by your study doctor 32 33 Additionally at the end of every two cycles you will also have the following procedures 34 repeated:
35 - MRI or CT scan of the tumor(s)
36 - MIBG or PET scan. 37 - Bone marrow aspirations and examination (We will ask you if we can collect a 38 small amount of additional bone marrow that will be used for special research 39 testing of neuroblastoma cells if they are present. There is a separate consent 40 for this at the end of this form.)
41 42 If your cancer is responding and if you are not experiencing unacceptable side effects 43 from treatment, it will be up to your study doctor's discretion to continue treatment on 44 protocol beyond the six 21-day cycles of treatment described above (you may 45 continue this until you have progression, you no longer wish to continue, or your study 46 doctor decides it is not in your best interest). If you continue on drug past the six 21 47 day cycles, you will still be considered part of the study and you will still need to have 1 procedures done with every cycle as explained above. These follow ups include the 2 same tests and procedures as the preceding cycles did. We will also continue to 3 collect information from these tests and procedures and on your treatment and 4 outcomes.  
5 6 As a part of your treatment you may have a surgical operation to remove as much of 7 the tumor as possible. You will be asked by the pediatric surgeon to sign a separate 8 surgical consent form, which will review the risks of that surgical procedure. If the 9 tumor is obtained by surgery for routine (non-study) care, you will be asked if some of 10 the tumor can be saved for special research testing of cancer cells if they are present. 11 There is a separate consent for this at the end of this form.  
12 13 After you are finished taking DFMO, the study doctor will ask you to visit the office for 14 a follow-up visit about 30 days after your last dose of DFMO. During this follow up visit 15 you will have a physical exam, blood tests, urine tests, bone marrow test, and 16 radiologic evaluations (MIBG scan {if done at screening}, CT scans and/or MRI) to 17 assess the response of the tumor. You will then be followed to see how you are doing 18 every 3 months for one year, then yearly until 5 years after stopping the study drug. 19 We will do this follow up either by phone or e-mail.  
20 21 All required radiology scans (MIBG's, PET's and MRI/CT's), must be done at the study 22 institution, [INSERT INSTITUTION NAME] unless otherwise approved by the sponsor.  
23 If [INSERT INSTITUTION NAME] is not your home institution, all other care (excluding 24 the previously mentioned) can be done at your home institution at the discretion of 25 your study doctor.  
26

28 29 DFMO will be taken orally (by mouth) twice a day, once in the morning and once in the 30 evening every day that you are on the study. DFMO is a tablet that will be supplied to 31 you. If you cannot swallow tablets you will be given instructions on how to crush and take 32 the study drug. DFMO may not be mixed with orange or grapefruit juice. You will be given 33 a handout that will have the directions written out as well as a list of recommended juices 34 and foods to use when mixing the DFMO. This handout will also include instructions for 35 storing DFMO.  
36 37 Bortezomib will be given intravenously (by IV) once a day on days 1, 4, and 8 of each 21 38 day cycle.  
39 40 You will be asked to keep a daily diary of the study drug and dose you are taking; this 41 diary will be provided to you by the study doctor, and will need to be returned to the study 42 doctor at the end of each cycle.  
43 44 Throughout the study, you will be asked to report any difficulties or side effects that you 45 experience, regardless of whether or not you feel they are related to, or caused by, the 46 study medication. It is very important for you to discuss any difficulties or side effects with 47 your study doctor.  
48 1 If you have any significant side effects or problems, you should promptly contact your 2 home treating oncologist. Your home treating oncologist will then decide if you should 3 come in to the hospital. In addition you will need to contact your study doctor. Your study 4 doctor will determine what you should do about your study drug doses. Doses may be 5 reduced, delayed or omitted if you have toxicities or side effects. If your condition worsens 6 during the study, your study doctor may remove you from the study.  
7 8 While you are on this study, there are certain medications and treatments that you will not 9 be allowed to take. Those include any other cancer killing agents or chemotherapy, any 10 other investigational (study) drugs, immunotherapy, hormonal therapy, and targeted 11 therapies. Please discuss all medications that you are currently taking or wish to take 12 with your study doctor.  
13 14 **PROCEDURES AND ASSESSMENTS FOR THIS STUDY**
15  
| Pre                                                   | Cycles 1   | Cycles 2-6   | Subsequ ent   | Follow Up   |     |     |     |                |    |    |    |
|-------------------------------------------------------|------------|--------------|---------------|-------------|-----|-----|-----|----------------|----|----|----|
| Day                                                   | Day        | Day          | Day           | Day         | Day | Day | Day | Cycles         |    |    |    |
| 1                                                     | 4          | 8            | 15            | 1           | 4   | 8   | 15  | End  of  Cycle |    |    |    |
| Informed consent                                      | X          |              |               |             |     |     |     |                |    |    |    |
| Prior therapy  review                                 | X          | X            |               |             |     |     |     |                |    |    |    |
| Physical  examination and                             | X          | X            | X             | X           | X   | X   | X   | X              | X  |    |    |
| history Lansky Score                                  | X          | X            | X             | X           |     |     |     |                |    |    |    |
| Vital signs                                           | X          | X            | X             | X           | X   | X   | X   | X              | X  | X  |    |
| Blood tests                                           | X          | Xa           | X             | X           | X   | X   | X   | X              | X  |    |    |
| Pregnancy test if  indicated                          | X          | Xa           | X             | X           |     |     |     |                |    |    |    |
| CT or MRI Scan                                        | X          | Xb           | Xb            | Xb          |     |     |     |                |    |    |    |
| MIBG or PET                                           | X          | Xb           | Xb            | Xb          |     |     |     |                |    |    |    |
| Review of  Current                                    | X          | X            | X             | X           | X   | X   | X   | X              | X  | X  | X  |
| Medications Administration of  DFMOc                  | X          |             |              |            |    |    |    |               |   |   |    |
| Administration of  Bortezomibd                        | X          | X            | X             | X           | X   | X   | Xd  |                |    |    |    |
| Dispense (and                                         | X          | X            | Xe            |             |     |     |     |                |    |    |    |
| collect) drug  dosing diary Adverse Event  monitoring | X          | X            | X             | X           | X   | X   | X   | X              | X  | X  |    |
| Progression free  Survival                            | X          |              |               |             |     |     |     |                |    |    |    |  
| Urine Tests               | X                                                             | X   | X   | X   | X   |
|---------------------------|---------------------------------------------------------------|-----|-----|-----|-----|
| Audiogram  (hearing test) | X                                                             | Xf  | Xf  | Xf  |     |
| Bone Marrow^              | X                                                             | Xb  | Xb  | Xb  |     |
| Optional Blood  Samples^  | X                                                             | X   | X   |     |     |
| Optional Urine  Samples^  | X                                                             | X   | X   |     |     |
| a                         |                                                               |     |     |     |     |
| 1                         | If not already done in the 5 days prior to first dose of drug |     |     |     |     |  
a 1 *If not already done in the 5 days prior to first dose of drug* b 2 At end of cycles 2, 4, and 6, then every 2 cycles and as clinically indicated c 3 *DFMO given twice daily every day on study unless a hold is indicated* d 4 *Bortezomib given on Days 1, 4, and 8 of each cycle unless a hold is indicated* e 5 *If early withdrawal or not previously collected* f 6 *At the ends of cycles 2, 6 and then yearly or as indicated* 7 *^Separate consent at end for additional samples* 8
Clinical trial: NCT02139397
Section: Purpose of Research
Subsections: 2 Why Is This Research Study Being Conducted?

3 4 The purpose of this research study is to evaluate an investigational drug (DFMO) in 5 combination with bortezomib, for relapsed and refractory neuroblastoma. DFMO is an 6 investigational drug because it has not been approved by the U.S. Food and Drug 7 Administration (FDA). Bortezomib, although a drug approved by the FDA for other 8 cancers, is investigational for treatment of neuroblastoma in this study. This study will 9 look at the safety and tolerability of DFMO in combination with bortezomib as well as the 10 tumors response to this study drug.  
11 12 DFMO was shown to be effective in inhibiting tumor growth in adult colon cancers. DFMO
13 has been tested in multiple adult clinical trials and one pediatric trial. Laboratory testing 14 in neuroblastoma suggests that this drug may be effective in treating this disease.  
15 16 Subjects signing this consent form will be given a new formulation of DFMO that has not 17 previously been used in children. This new formulation contains the same active 18 ingredient as the previous formulation; however it is made by a different manufacturer 19 and so it is possible that the DFMO may be absorbed differently by the body.  
20 21 The first portion of this study is a Phase I trial. A phase I trial is a trial that is in the first 22 stage of testing in human subjects. The purpose of a Phase I study is to test for safety 23 and to find the highest dose of the drug that subjects can tolerate (optimal dosing). 24 Optimal dosing of DFMO in combination with bortezomib in pediatric patients is not known 25 at this time. This is the first time DFMO has been given with bortezomib to children. Read 26 the sections on risks and benefits carefully and be sure you understand them.  
27 28 This study will be using increasing doses that will continue until unacceptable toxicities 29 are identified. If there are toxicities in one group of subjects, that dose may be repeated.  
30 There will be a hold in enrollment after each 3 subjects (each cohort) are enrolled in order 31 to monitor that dose for safety and toxicities.  
32 33 All children will receive the same dose of bortezomib.  
34 35 Because of the way subjects are enrolled, there is a possibility that even if you qualify for 36 this study, there may not be a space available for you to start on study.  
37 38 You may receive a different dose of DFMO than other subjects depending on when you 39 start on study. We cannot guarantee the dose that you will be given until you start on the 40 study. Both you and the study doctor will know what dose you receive. The dose you 41 receive may be so low that it has no effect or so high that you have side effects you cannot 42 tolerate.  
43
Clinical trial: NCT02139397
Section: Voluntary Participation
Subsections: 30 Statement Of Consent

31 32 I have been given and have read the information in this consent form (or it has been read 33 to me).  
34 35 All of my/my child's questions about the study and my/my child's participation in it have 36 been answered. Should I/my child have any further questions about the research, I may 37 contact the person conducting the study at the address and telephone number given 38 below:
39 40 [Study Contact Name]
41 [Address]
42 [City, State Zip code] 43 [Phone Number(s)]
44 45 My/my child's participation is voluntary and I/my child may refuse to participate or 46 withdraw at any time without penalty or prejudice to my/my child's present and/or future 47 care.  
1 2 I agree to participate/allow my child to participate in this study and I understand that I will 3 receive a signed copy of this form.  
4 5 I authorize the release of my/my child's medical information for research or regulatory 6 purposes to the sponsor, The Neuroblastoma and Medulloblastoma Translational 7 Research Consortium, Spectrum Health Hospitals and its affiliates, KC Pharma and its 8 affiliates, the FDA, other federal (U.S.) agencies, governmental agencies in other countries, and WIRB® 9 .  
10
Clinical trial: NCT02139397
Section: Withdrawal from Study
Subsections: 44 Can You Withdraw Or Be Withdrawn From This Study?

45 46 Participation in this study is voluntary. You are not obligated to participate in this 47 research. You are free to withdraw your consent at any time. Your withdrawal, or refusal  
1 to participate, will not affect your current or future medical care in any way. Your decision 2 will not result in any penalty or loss of benefits to which you are entitled.  
3 4 It is important to tell the study doctor if you are thinking about stopping so any risks from 5 the study drug can be evaluated by your study doctor. Another reason to tell your study 6 doctor that you are thinking about stopping is to discuss what follow-up care and testing 7 could be most helpful for you.  
8 9 You will be told of any significant new findings that develop during the study that may 10 affect your willingness to participate in the study. You may be asked to sign a new 11 consent form to continue in the study.  
12 13 Your study doctor or the sponsor may decide to take you out of the study at any time 14 without your consent if any of the following occur or for other reasons:
15 16 - You do not meet the criteria to take part in the study. 17 - The side effects of the study drug are too harmful for you. 18 - You need a treatment that is not allowed on this study. 19 - Your tumor worsens. 20 - You become pregnant. 21 - The study doctor believes it is in your best interest. 22 - New information becomes available that would suggest that continuing in this study 23 would not be in your best interest.  
24 - You do not consent to continue in the study after being told of changes in the 25 research that may affect you.  
26 - The study is stopped. 27 - Or for any other reason.  
28 29 The Neuroblastoma and Medulloblastoma Translational Research Consortium, Spectrum 30 Health Hospitals, KC Pharma (the maker of DFMO), Western Institutional Review Board, 31 or the FDA has the right to stop this study at any time. They may stop the study without 32 your agreement based on medical information available to them.  
33 34 What About Confidentiality?  
35 36 We will do our best to make sure that your personal medical information will be kept 37 private. However, we cannot guarantee total privacy. Your personal information may be 38 given out if required by law.  
39 40 If information from this study is published or presented at scientific meetings, your name 41 and other personal information will not be used.  
42 43 Each subject in this trial will be identified by a unique identifier that will be used on all 44 report forms and any other material submitted to the NMTRC. Report Forms for this study 45 will be both paper and electronic. Electronic data will be stored in a secure data center.  
46 Your medical records are available to those caring for you at this hospital. Other people 1 or groups who may see or copy your medical record because you are participating in this 2 study include:
3 4 - The Neuroblastoma and Medulloblastoma Translational Research Consortium 5 (NMTRC), affiliates of the NMTRC, and the NMTRC010B study committee 6 - Spectrum Health Hospitals and its affiliates 7 - KC Pharma and their affiliates 8 - The U.S. Food and Drug Administration
- The Western Institutional Review Board® (WIRB® 9 )
10 - The Spectrum Health Institutional Review Board 11 - Department of Health and Human Services (DHHS) agencies 12 13 Otherwise your name and other medical information that identifies you will not be released 14 without your written permission, unless required by law. If results of this study are 15 published, your identity will remain confidential.  
16 17 A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as 18 required by U.S. Law. This Web site will not include information that can identify you. At 19 most, the Web site will include a summary of the results. You can search this Web site 20 at any time.  
21 22 Please refer to the separate authorization (HIPAA) form that explains more specifically 23 how your personal health information will be used.  
24 25 What Happens If You Are Injured?  
26 27 Participating in research may result in an injury or illness. Medical treatment related to 28 an injury or illness will be available at your treating institution, but such treatment may not 29 be free of charge. No funding has been set aside to pay for the costs of treating an injury 30 or illness that results from this study. Your medical insurance may pay for such treatment, 31 but you may ultimately be billed for payment.  
32 33 Ask the study doctor for more information about this. We also encourage you to 34 determine your health insurer's policy about paying for treatment in a research study.  
35 36 By signing this consent form, you are not giving up any legal rights.  
37 38 [INSERT INSTITUTIONAL LANGUAGE HERE]
39 40 Contact Information 41 42 Contact [Study Contact Name] at [Phone Number(s)] for any of the following reasons:
43 - if you have any questions about your participation in this study, 44 - if at any time you feel you have had a research-related injury, illness or a reaction 45 to the study drug, or 46 - if you have questions, concerns or complaints about the research.  
47
1 If you have questions about your rights as a research subject or if you have questions, 2 concerns, input or complaints about the research, you may contact:
3 Western Institutional Review Board® (WIRB® 4 )
5 1019 39th Avenue SE Suite 120 6 Puyallup, Washington 98374-2115 7 Telephone: 1-800-562-4789 or 360-252-2500 8 E-mail: Help@wirb.com 9 10 WIRB is a group of people who perform independent review of research.  
11 12 WIRB will not be able to answer some study-specific questions, such as questions about 13 appointment times. However, you may contact WIRB if the research staff cannot be 14 reached or if you wish to talk to someone other than the research staff.  
15