Clinical trial: NCT01064466
Section: Alternatives
Subsections: What Is The Usual Approach To My Small Cell Lung **Cancer?**|What Are My Other Choices **If I Do Not Take Part In This Study?**

You are being asked to take part in this research study because you have had lung tissue biopsy for your small cell lung cancer. People who are not in a research study may be treated with chemotherapy drugs after lung tissue biopsy. There are three FDA-approved drugs (Etoposide Injection plus Topotecan Capsule) that are commonly used. For patients who receive the usual approach for this cancer about 70 out of 100 may be alive and free of cancer at one year.

If you decide not to take part in this study, you have other choices. For example:
- you may choose to have the usual approach described above - you may choose to take part in a different study if one is available
- or you could decide not to be treated for cancer
Clinical trial: NCT01064466
Section: Confidentiality
Subsections: Who Will See My Medical Information?|How Will Information About Me Be Kept Private?

Your privacy is very important to us and the researchers will make every effort to protect it. Your information may be given out if required by law. For example, certain states require doctors to report to health boards if they find a disease like tuberculosis. However, the researchers will do their best to make sure that any information that is released will not identify you. Some of your health information, and/or information about your specimen, from this study will be kept in a central database for research. Your name or contact information will not be put in the database.  
There are organizations that may inspect your records. These organizations are required to make sure your information is kept private, unless required by law to provide information. Some of these organizations are:  
- The Medicine Invention Design, Inc. and other drug companies supporting this study.  
- The Institutional Review Board, IRB, is a group of people who review the research with the goal of protecting the people who take part in the study.  
- The Food and Drug Administration in the U.S. and similar agencies in other countries involved in the study.

Your privacy is very important to the researchers, and they will make every effort to protect it. Here are just a few of the steps they will take: 1) When your sample is sent to the researchers, no information identifying you (such as your name) will be sent. Samples will be identified by a unique code only.  
2) The list that links the unique code to your name will be kept separate from your sample and health information. Any Biobank and MIDINC Clinical Research Multiple Group staff with access to the list must sign an agreement to keep your identity confidential.  
3) Researchers to whom the MIDINC Clinical Research Multiple Group sends your sample and information will not know who you are. They must also sign an agreement that they will not try to find out who you are.  
4) Information that identifies you will not be given to anyone, unless required by law. 5) If research results are published, your name and other personal information will not be used.
Clinical trial: NCT01064466
Section: Duration of Study Involvement
Subsections: How Long Will I Be In **This Study?**

You will receive the study drugs for six months if you are in Group 1 and in Group 2. After you finish the study drugs, you will be asked to see your study doctor for follow-up examinations for 2 years. Your study doctor would like to continue to watch you for side effects and follow your condition for the rest of your life.
Clinical trial: NCT01064466
Section: Participant's Rights
Subsections: 21 Cfr § 50.20 -- General Requirements For Informed Consent.|21 Cfr § 50.25 -- Elements Of Informed Consent.|21 Cfr§50.27 Documentation Of Informed Consent.|What Are My Rights In This Study?

Except as provided in §50.23 and §50.24, no investigator may involve a human being as a subject in research covered by these regulations unless the investigator has obtained the legally effective informed consent of the subject or the subject's legally authorized representative. An investigator shall seek such consent only under circumstances that provide the prospective subject or the representative sufficient opportunity to consider whether or not to participate and that minimize the possibility of coercion or undue influence. The information that is given to the subject or the representative shall be in language understandable to the subject or the representative. No informed consent, whether oral or written, may include any exculpatory language through which the subject or the representative is made to waive or appear to waive any of the subject's legal rights, or releases or appears to release the investigator, the sponsor, the institution, or its agents from liability for negligence.

(a) Basic elements of informed consent. In seeking informed consent, the following information shall be provided to each subject:
(1) A statement that the study involves research, an explanation of the purposes of the research and the expected duration of the subject's participation, a description of the procedures to be followed, and identification of any procedures which are experimental.  
(2) A description of any reasonably foreseeable risks or discomforts to the subject. (3) A description of any benefits to the subject or to others which may reasonably be expected from the research.  
(4) A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject.  
(5) A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained and that notes the possibility that the Food and Drug Administration may inspect the records.  
(6) For research involving more than minimal risk, an explanation as to whether any compensation and an explanation as to whether any medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be obtained.  
(7) An explanation of whom to contact for answers to pertinent questions about the research and research subjects' rights, and whom to contact in the event of a research-related injury to the subject.  
(8) A statement that participation is voluntary, that refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and that the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled.  
(b) Additional elements of informed consent. When appropriate, one or more of the following elements of information shall also be provided to each subject:
(1) A statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant) which are currently unforeseeable.  
(2) Anticipated circumstances under which the subject's participation may be terminated by the investigator without regard to the subject's consent.  
(3) Any additional costs to the subject that may result from participation in the research. (4) The consequences of a subject's decision to withdraw from the research and procedures for orderly termination of participation by the subject.  
(5) A statement that significant new findings developed during the course of the research which may relate to the subject's willingness to continue participation will be provided to the subject.  
(6) The approximate number of subjects involved in the study.  
(c) When seeking informed consent for applicable clinical trials, as defined in 42 U.S.C.  
282(j)(1)(A), the following statement shall be provided to each clinical trial subject in informed consent documents and processes. This will notify the clinical trial subject that clinical trial information has been or will be submitted for inclusion in the clinical trial registry databank under paragraph (j) of section 402 of the Public Health Service Act. The statement is: "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 the results. You can search this Web site at any time."
(d) The informed consent requirements in these regulations are not intended to preempt any applicable Federal, State, or local laws which require additional information to be disclosed for informed consent to be legally effective.  
(e) Nothing in these regulations is intended to limit the authority of a physician to provide emergency medical care to the extent the physician is permitted to do so under applicable Federal, State, or local law.

(a) Except as provided in §56.109(c), informed consent shall be documented by the use of a written consent form approved by the IRB and signed and dated by the subject or the subject's legally authorized representative at the time of consent. A copy shall be given to the person signing the form.  
(b) Except as provided in §56.109(c), the consent form may be either of the following: (1) A written consent document that embodies the elements of informed consent required by
§50.25. This form may be read to the subject or the subject's legally authorized representative, but, in any event, the investigator shall give either the subject or the representative adequate opportunity to read it before it is signed.  
(2) A short form written consent document stating that the elements of informed consent required by §50.25 have been presented orally to the subject or the subject's legally authorized representative. When this method is used, there shall be a witness to the oral presentation. Also, the IRB shall approve a written summary of what is to be said to the subject or the representative. Only the short form itself is to be signed by the subject or the representative. However, the witness shall sign both the short form and a copy of the summary, and the person actually obtaining the consent shall sign a copy of the summary. A copy of the summary shall be given to the subject or the representative in addition to a copy of the short form.  
| Phase 2 SNP Study Consent Form 4 Study Title for Study Participants: 4 Official Study Title for Internet Search on http://www.ClinicalTrials.gov: 4 What is the usual approach to my small cell lung cancer? 5 What are my other choices if I do not take part in this study? 5 Why is this study being done? 5 What are the study groups? 5 How long will I be in this study? 6 What extra tests will I have if I take part in this study? 6 What possible risks can I expect from taking part in this study? 6 What possible benefits can I expect from taking part in this study? 7 Can I stop taking part in this study? 8 What are my rights in this study? 8 What are the costs of taking part in this study? 8 What happens if I am injured or hurt because I took part in this study? 8 Who will see my medical information? 8 Where can I get more information? 9 Who can answer my questions about this study? 9 ADDITIONAL STUDIES SECTION: 9 This section is about an optional study you can choose to take part in 9   |
|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Possible Side Effects of Etoposide 12 Possible Side Effects of Topotecan 13 My Signature Agreeing to Take Part in the Main Study 14                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 |

Taking part in this study is your choice. No matter what decision you make, and even if your decision changes, there will be no penalty to you. You will not lose medical care or any legal rights. For questions about your rights while in this study, call the Medicine Invention Design, Inc. Institutional Review Board (IRB) at 1-301-222-7143.
Clinical trial: NCT01064466
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: What Possible Risks Can I Expect From Taking Part **In This Study?**|What Possible Benefits Can I Expect From Taking Part In This **Study?**|What Are The Costs Of Taking Part In This Study?|What Happens If I Am Injured Or Hurt Because I Took Part In This Study?|What Are **The Possible Risks?**|What Are The Possible Benefits?|Are There Any Costs Or Payments?|Common, Some May Be Serious|Occasional, Some May Be Serious In 100 People Receiving Etoposide, From 4 To 20 May Have:|Rare, And Serious In 100 People Receiving Etoposide, 3 Or Fewer May Have:

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.  
6 of 14  
- The usual chemotherapy drugs may not be better, and could be possibly worse, than receiving the chemotherapy drugs.
The study drugs 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, urine, and tissue, and will let you know if changes occur that may affect your health. There is also a risk that you could have side effects from the usual chemotherapy drugs and the study chemotherapy drugs.  
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. Study Group 1 and Group 2 - Table of Possible Side Effects of the usual chemotherapy and the study chemotherapy for this type of cancer:  
- See Table of Possible Side Effects of Etoposide (See Page 13)
- See Table of Possible Side Effects of Topotecan (See Page 15)
Let your study doctor know of any questions you have about possible side effects. You can ask the study doctor questions about side effects at any time.  
Reproductive risks: You should not get pregnant, breastfeed, or father a baby while in this study. The drugs used in this study could be very damaging to an unborn baby. Check with the study doctor about what types of birth control, or pregnancy prevention, to use while in this study.

It is not possible to know at this time if the study chemotherapy is better than the usual chemotherapy, so this study may or may not help you. This study will help researchers learn things that will help people in the future.  
The classic oncology drug clinical trials must have placebo group, but the cancer patients in the placebo group will be equivalent to give up oncology drug treatments, so the placebo group cancer patients will surely die. But, because every SNP has biallelic alleles ALL-OR-NONE characteristics, in same one SNP clinical trial, toward same one therapeutic effect or same one side effect, all two of double-blind random separate group patient drug target gene SNPs will be the same. Therefore, only need set up two double-blind random separate groups of patients, and then treat same one cancer with two different combination chemotherapies including same oncology drugs separately in two different treating groups; in these SNP-pharmacogenomics clinical trials, the placebo group will surely be avoided. Like as this, even in the SNP clinical trial stage, also can rescue much many cancer patients' lives. This clinical project's success means that the cancer organ system limitation of oncology drug chemotherapy will be broken-through, meanwhile, the cancer patient population who can use specific one oncology drug will be expanded. Because based on SNP biallelic alleles ALL-OR-NONE characteristics, if the same Oncology Drug Therapeutic Effect Target Gene SNP is detected in different cancers, when using the same drug, any kinds of cancers having the same drug therapeutic effect target gene SNP will have same therapeutic effect; so, any kinds of cancers having the same drug therapeutic effect target gene SNP will be suitable for using the same drug to treat.

The usual chemotherapy drugs and the study chemotherapy drugs will be supplied at charge by your insurance company while you take part in this study. The cost of getting the drugs ready and giving them to you is not provided by you so your insurance company will have to pay for this. It is possible that the usual chemotherapy drugs and the study chemotherapy drugs may not continue to be supplied while you are on the study. Although not likely, if this occurs, your study doctor will talk to you about your options. Your health plan / insurance company will need to pay for all of the other costs of treating your cancer while in this study, including the cost of managing any side effects. Before you decide to be in the study, you should check with your health plan or insurance company to find out exactly what they will pay for. You will not be paid for taking part in this study.

If you are injured or hurt as a result of taking part in this study and need medical treatment, please tell your study doctor. The study sponsors will not offer to pay for medical treatment for injury. Your insurance company may be willing to pay for study-related injury. If you have no insurance, you would be responsible for any costs. If you feel this injury was a result of medical error, you keep all your legal rights to receive some help for this even though you are in a study.

1) There is a risk that someone could get access to the personal information in your medical records or other information the researchers have stored about you.  
2) There is a risk that someone could trace the information in a central database back to you. Even without your name or other identifiers, your genetic information is unique to you. The researchers believe the chance that someone will identify you is very small, but the risk may change in the future as people come up with new ways of tracing information.  
3) In some cases, this information could be used to make it harder for you to get or keep a job or insurance. There are laws against the misuse of genetic information, but they may not give full protection. There can also be a risk in knowing genetic information. New health information about inherited traits that might affect you or your blood relatives could be found during a study. The researchers believe the chance these things will happen is very small but cannot promise that they will not occur.

You will not benefit from taking part. The researchers, using the samples from you and others, might make discoveries that could help people in the future.

There are no costs to you or your insurance. You will not be paid for taking part. If any of the research leads to new tests, drugs, or other commercial products, you will not share in any profits.

In 100 people receiving Etoposide, more than 20 and up to 100 may have:
- Infection, especially when white blood cell count is low - Anemia which may require transfusion - Bruising, bleeding - Sores in mouth which may cause difficulty swallowing - Diarrhea, loss of appetite, nausea, vomiting - Tiredness - Fever - Chills
- Hair loss

- Heart failure or heart attack which may cause chest pain, shortness of breath, swelling of ankles, and tiredness
- Liver damage which may cause yellowing of eyes and skin, swelling
- Severe skin rash with blisters and peeling which can involve inside of mouth and other parts of the body

- Cancer of bone marrow caused by chemotherapy
- Allergic reaction which may cause rash, low blood pressure, wheezing, shortness of breath, swelling of the face or throat Possible Side Effects of Topotecan (Table Version Date: August 4, 2016)
COMMON, SOME MAY BE SERIOUS
In 100 people receiving Topotecan, more than 20 and up to 100 may have:
- Anemia which may require a blood transfusion - Constipation, diarrhea, nausea, vomiting - Fever - Pain - Bruising, bleeding - Infection, especially when white blood cell count is low - Tiredness - Shortness of breath
- Hair loss OCCASIONAL, SOME MAY BE SERIOUS
In 100 people receiving Topotecan, from 4 to 20 may have:
- Blockage of the bowels
- Sores in mouth which may cause difficulty swallowing
- Headache
- Cough - Rash RARE, AND SERIOUS
In 100 people receiving Topotecan, 3 or fewer may have:
- Allergic reaction which may cause rash, low blood pressure, wheezing, shortness of breath, swelling of the face or throat
- Swelling of the bowels which may require surgery
- Scarring of the lungs
Clinical trial: NCT01064466
Section: Procedures
Subsections: What Are The Study Groups?|What Extra Tests Will I Have If I Take Part In This Study?|What Is Involved?

This study has two study groups.  
- Group 1 will get the usual chemotherapy drugs to treat this type of cancer: Etoposide Injection plus Topotecan Capsule o Etoposide Injection will be given you into a vein at every day 1-5.  
This will take 1 hours and will be given to you through a small portable pump.  
o You will receive Topotecan Capsule into a mouth at day 1-5. o This schedule will be repeated 21 days later. o This chemotherapy will be repeated for 90 days.  
- Group 2 will get the study chemotherapy drugs to treat this type of cancer: Etoposide Capsule plus Topotecan Capsule o You will receive Etoposide Capsule into a mouth at day 1-5. o You will receive Topotecan Capsule into a mouth at day 1-5.  
o This schedule will be repeated 21 days later.  
o This chemotherapy will be repeated for 90 days.
A computer will by chance assign you to treatment groups in the study. This is called randomization. This is done by chance because no one knows if one study group is better or worse than the other. Neither you nor your doctor can choose which group you will be in.  
Another way to find out what will happen to you during this study is to read the chart below. Start reading at the left side and read across to the right, following the lines and arrows.

If you are assigned to Group 1, all of the tests you will have are part of the usual approach for your cancer. If you are assigned to Group 2, all of the tests you will have are part of the study approach for your cancer. There are blood, urine, and tissue tests that you will need to have:
- Sequence precisely each target gene DNA whole chain in cancer tissue like as following:
DNA Topoisomerase II, DNA Topoisomerase I.  
- Correlate Topoisomerase II Gene Single Nucleotide Polymorphisms (SNPs) to Using Etoposide Therapeutic Effects of Treating Small Cell Lung Cancer (SCLC), based on precisely sequencing drug target gene via Cancer Tissue DNA.  
- Sequence precisely each target gene DNA whole chain in peripheral blood like as following:
CYP450 3A4.  
- Correlate CYP450 3A4 Gene Single Nucleotide Polymorphisms (SNPs) to Using Etoposide Side Effects of Treating Small Cell Lung Cancer (SCLC), based on precisely sequencing drug target gene via Peripheral Blood DNA.  
- You will need lung tissue biopsy test at least one time. - You will need image test at least one time per month. - If you have an allergic reaction to oncology drugs, you will have an extra blood test. - You will need urine tests every week while you are taking oncology drugs.  
- You will need blood tests every week while you are taking oncology drugs.  
Your insurance company will be charged for the blood, urine, and tissue biopsy tests related to oncology drugs.

If you agree to take part, here is what will happen next: 1) A sample from the tissue that was collected at the time of your biopsy will be sent to the Biobank.
2) Your sample and some related information may be stored in the Biobank along with samples and information from other people who take part. The samples will be kept until they are used up.  
3) Qualified researchers can submit a request to use the materials stored in the Biobank. A
science committee at the clinical trials organization, and/or the MIDI, will review each request. There will also be an ethics review to ensure that the request is necessary and proper. Researchers will not be given your name or any other information that could directly identify you.  
4) Neither you nor your study doctor will be notified when research will be conducted or given reports or other information about any research that is done using your samples.  
5) Some of your genetic and health information may be placed in central databases that may be public, along with information from many other people. Information that could directly identify you will not be included.
Clinical trial: NCT01064466
Section: Purpose of Research
Subsections: Phase 2 **Snp Study Consent Form** Study Title For Study Participants:|Why Is This Study Being Done?

Testing the SNPs of the study chemotherapy, comparing to the SNPs of the usual chemotherapy in small cell lung **cancer**
Pharmacogenomics IND EXEMPT SNP Clinical Study - Etoposide Injection and Single Nucleotide Polymorphisms (Drugs-SNPs)

The purpose of this study is to test any good and bad effects of the study chemotherapy drugs (Etoposide Capsule plus Topotecan Capsule) compared to the usual chemotherapy drugs (Etoposide Injection plus Topotecan Capsule). The study group drugs could cause therapeutic effects of chemotherapy by preventing your cancer from returning or they could cause side effects or reduce the benefits of chemotherapy. This study will allow the researchers to know whether the study chemotherapy drugs are better, the same or worse than not doing so. Correlate oncology drugs' targets' genes' single nucleotide polymorphisms (SNPs) to using oncology drugs therapeutic effects and side effects of treating small cell lung cancer (SCLC), based on precisely sequencing oncology drugs' targets' genes. The chemotherapy efficacy can arrive higher than the 90% Effective Dose (ED90) level. The chemotherapy risk can arrive lower than the 10% Lethal Dose (LD10) level. There will be about 600 people taking part in this study.
Clinical trial: NCT01064466
Section: Voluntary Participation
Subsections: Additional Studies Section: This Section Is About An Optional Study **You Can Choose To Take Part In**|Optional Sample Collections For Biobanking For Possible Future Studies|My Signature **Agreeing To Take Part In The Main Study**

You can still take part in the main study even if you say 'no' to this study. If you sign up for but cannot complete this study for any reason, you can still take part in the main study.

Researchers are trying to learn more about cancer, diabetes, and other health problems. Much of this research is done using samples from your tissue, blood, urine, or other fluids. Through these studies, researchers hope to find new ways to prevent, detect, treat, or cure health problems.  
Some of these studies may be about genes. Genes carry information about features that are found in you and in people who are related to you. Researchers are interested in the way that genes affect how your body responds to treatment. The researchers ask your permission to store and use your samples and health information for medical research. The research that may be done is unknown at this time. Storing samples for future studies is called 'biobanking'. The Biobank is being run by the MIDINC Clinical Research Multiple Group and supported by the Medicine Invention Design, Inc. (MIDI).

I have read this consent form, or had it read to me. I have discussed it with the study doctor and my questions have been answered. I will be given a signed copy of this form. I agree to take part in the main study and in the optional study if I have circled "Yes". Participant's signature _________________________________________ Date of signature_____________________________________ Study Doctor's signature_________________________________________ Date of signature_____________________________________ Study Nurse / Assistant's signature_________________________________________ Date of signature_____________________________________
Clinical trial: NCT01064466
Section: Withdrawal from Study
Subsections: Can I Stop Taking Part **In This Study?**|What If I Change My Mind?

Yes. You can decide to stop at any time. If you decide to stop for any reason, it is important to let the study doctor know as soon as possible so you can stop safely. If you stop, you can decide whether or not to let the study doctor continue to provide your medical information to the organization running the study. The study doctor will tell you about new information or changes in the study that may affect your health or your willingness to continue in the study. The study doctor may take you out of the study:  
- If your health changes and the study is no longer in your best interest
- If new information becomes available
- If you do not follow the study rules - If the study is stopped by the sponsor, IRB, or FDA

If you decide you no longer want your samples to be used, you can call the study doctor via 1301-222-7143 who will let the researchers know. Then, any sample that remains in the bank will no longer be used. Samples or related information that have already been given to or used by researchers will not be returned.