BTOG2 PATIENT INFORMATION SHEET

BTOG2: A British Thoracic Group phase III trial of gemcitabine plus at 80mg/m2 versus gemcitabine plus cisplatin at 50mg/m2 versus gemcitabine plus AUC 6 in stage IIIB/IV non-small cell lung cancer

Chief Investigator: Prof David Ferry

Local Investigator:

Dear Patient

You are being offered the opportunity to take part in a clinical research study. About 1350 patients will participate in this key study and it is expected to take about 36 months to complete recruitment. This leaflet gives you some information about the study and why it is being done, and what the potential benefits and risks may be. It is important that you read and understand this information leaflet before you decide whether or not to take part. If you have any questions of any kind about this study you should ask your doctor.

Why have I been chosen and what is the purpose of the study? Your doctor has told you that you have non-small cell lung cancer. Although your disease can not be cured, treatment with chemotherapy can improve symptoms and prolong survival. Although we know that chemotherapy with platinum containing anti-cancer drugs are the best treatment we still do not know which platinum drugs are the best or the amount of drug which produces the best results. This is important because higher doses of anti-cancer drugs have worse side effects than lower doses of the same drug. However a higher dose may be worthwhile if it works better to prolong life and control symptoms than the lower dose. This study has been set up to discover which of the two commonly used platinum agents, cisplatin or carboplatin, is the best and to find out if cisplatin 80 mg/m2 is better than 50 mg/m2 in combination with gemcitabine.

Do I have to take part in the study? Your participation in this study is entirely voluntary. You may choose not to participate or you may withdraw from the study at any time. You do not have to give any reason for your decision. Your doctor will continue to treat you with the best means available.

How would your treatment be chosen if you decide to participate? Your doctor cannot choose which of the three treatment regimens you will receive. Your treatment will be chosen at random by a computer, based at the BTOG2 Study Office. This procedure called “Randomisation” means that everyone has an equal chance of getting any of the three treatment arms. It also ensures that the three treatment groups will be comparable and that the trial is as fair a test of the treatments as possible.

What will the treatment involve? You will be given a complete physical examination and your medical history will be taken. Scans using X-rays will be done to look at your disease status. Blood samples (approximately

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40mls or 2 tablespoons per visit) will be taken and if you are a woman of childbearing potential, a pregnancy test will be done.

Once you have signed the consent document and the tests outlined above indicate it is safe for you to have the study chemotherapy, you will begin the treatment you have been allocated. Treatment consists of the chemotherapy drugs given through a drip into your vein on the 1st and 8th day of a 21-day treatment cycle. Up to 4 treatment cycles may be given.

The dose of gemcitabine and cisplatin are dependent on your height and weight that are used to calculate your body surface area (m2). The greater your body surface area the more milligrams of drug are required. However in the case of carboplatin, dose used is dependent on kidney function. This is because carboplatin is removed from your body principally by your kidneys; the better your kidneys work the higher the dose of carboplatin needed.

One Treatment Cycle

DayDay 1 1 DayDay 8 8 DayDay 21 21

Treatment Arm A Gem Cis Gem 2 80mg/m2 2 1250mg/m 1250mg/m

Treatment Arm B Gem Cis Gem 2 50mg/m2 1250mg/m2 1250mg/m

Treatment Arm C Gem Carb Gem 1250mg/m2 AUC 6 1250mg/m2

A maximum of 4 treatment cycles may be given

On Day One of each treatment cycle you will receive the chemotherapy drug Gemcitabine, (1250mg/m2) administered through a drip for approximately 30 mins.

You will then be given one of the following treatments you have been randomised to receive:- Cisplatin at 50 mg/m2 OR Cisplatin at 80 mg/m2 OR Carboplatin AUC 6 Administered through a drip for approximately one hour.

NOTE: If you receive cisplatin you will also receive extra fluids through the drip to help protect your kidneys from damage from the drug. Therefore the total time spent receiving cisplatin-based treatment is expected to be 6 hours and total time spent receiving carboplatin- based treatment is expected to be 1.5 hours.

On Day Eight of each treatment cycle you will receive the gemcitabine treatment only, again administered through a drip for approximately 30 mins.

Before each chemotherapy dose you will have a physical examination. You will be asked about any medical problems or changes in medication since the previous visit. Blood samples will be taken to see how the drugs are affecting you and to make sure it is still safe to continue to treat

Patient Information 28/8/07 Version 5 Page 2 Cancer Research UK Clinical Trials Unit Birmingham you. Also scans using X-rays will be taken to look at your disease status before treatment cycles 2, 3 and 4 begin.

At the end of the full treatment you will also have a physical exam, blood tests, and you will be asked about any medication changes or medical problems that you may have had during the previous month and a scan using X-rays will be taken, to look at your disease status. Any side effects continuing at that time will be followed until they have resolved or stabilized.

You will then be asked to return to clinic every 4 weeks up to a period of 6 months to find out if you have had any medical problems during the previous month. At these visits the doctor will perform a physical examination and a chest X-ray will be taken. The trial investigations may therefore involve one more CT scan and maybe 2-3 extra chest X-rays over and above the care your centre would offer to patients not in this clinical trial. Any potential health risk associated with these or any of the above scans is considered to be low for a patient with your medical condition.

The quality of life sub-study, what is involved? We are also interested in how your treatment might affect your quality of life and well being. We think it is very important to find out how people taking part in the study feel, both emotionally and physically and to study any side effects in some detail. At each clinic visit throughout your time on the study we would like you to complete a quality of life questionnaire booklet. These questionnaires will give us valuable information on how you are getting on and how the treatment is affecting you. If you are not given a booklet when you attend clinic, please remind your doctor. All questionnaires will be kept at the BTOG2 Study Office and analysed anonymously.

How important is it to provide all of this information? You are not obliged to complete all questions in the questionnaire booklet, however it is important we get as complete a picture as possible for the Quality of Life research. These are standard questionnaires and although some of the questions may seem repetitive, please try to complete all of the questions as best you can.

Flow chart of tests and procedures that will be carried out during the study

Before start Cycle 1 Cycle 1 Cycle 2-4 Cycle 2-4 End of Follow of (Day 1) (Day 8) (Day 1) (Day 8) treatment up each treatment (Between 4-6 Month x weeks after start 6 of last cycle) Read information x and sign consent. Physical x x x x examination Medical History x Blood tests x x Other current x x x x x x x medication Scanning Procedure x (x) x (Thoracic CT scan) cycle 2 only Scanning Procedure x x x x Chest X-Ray not needed (optional) cycle 2

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Toxicity assessment x x x x x Quality of Life x x x x

How long will the study last? How long you continue to get treatment will depend on how well your cancer responds to treatment and on whether or not you have any harmful side effects. You will receive up to 4 cycles of either cisplatin and gemcitabine or carboplatin and gemcitabine in total. Your treatment will be stopped if: • Your disease becomes worse • Your side effects are too severe • You or your doctor decide that the treatment you are getting is no longer in your best interest • New information is discovered showing that the treatment given is not in your best interest. • You decide to discontinue treatment. If your treatment is stopped, your doctor will continue to treat you with the best means possible.

What are the benefits of this research? If you take part in this study, it is possible that the therapy you get will shrink your cancer, help control lung cancer symptoms and prolong life, but this cannot be guaranteed. Even if you do not benefit directly from taking part in this study, information will be gained as a result of your participation that may help other cancer patients.

What are the side effects of treatment? Cisplatin: - Side effects that are common after treatment with cisplatin include: nausea and vomiting (you will receive tablets to prevent or help control this); effects on nerves, which may cause ringing in the ears and mild deafness (difficulty hearing in a crowded room) or tingling or numbness in the hands and feet, which may result in difficulties with some tasks, such as doing up buttons (these effects on nerves occur in a minority of patients and if they occur, happen near the end of the planned 4 courses of treatment); kidney toxicity (in order to ensure this does not become a major problem for you, your kidney function is checked before every cisplatin treatment); and finally temporary changes in blood test, which may make you more prone to infection and bruising.

Carboplatin: -Side effects that are common after treatment with carboplatin include: nausea and vomiting, (this is less common than with cisplatin and you will receive tablets to help this); fatigue; temporary changes in blood test, which may make you more prone to infection and bruising. This is more common with carboplatin than with cisplatin.

Gemcitabine: -Side effects that are common after treatment with gemcitabine include: mild nausea and vomiting (you will receive tablets to help this); fatigue; flu-like symptoms; skin rash, which can occasionally be quite severe and if it occurs you should contact your research nurse/consultant; and finally temporary changes in blood test which may make you more prone to infection and bruising.

In addition, there may be unknown (or unforeseeable) side effects that may occur. Your doctor will be watching you closely to see what side effects you have and can prescribe treatment to relieve your side effects if you need it. In addition, caution is necessary with all drugs used to

Patient Information 28/8/07 Version 5 Page 4 Cancer Research UK Clinical Trials Unit Birmingham treat cancer during pregnancy. The study drugs, like any anti-cancer drug, are likely to cause harm to the embryo, foetus or infant if administered during pregnancy or while nursing. Therefore, if there is a possibility you could become pregnant during the study, you must agree to practice birth control.

You will be informed of any new significant findings that develop with any of the study treatments that may affect your willingness to continue participation in this study.

Proteomic Sub-Study In addition to the BTOG2 main study we will be running a laboratory sub-study that aims to look for special proteins in the blood (research known as proteomics) of patients with lung cancer who go on to respond to treatment. It is hoped that through this research we may identify patients who are likely to respond to a particular treatment before it is given, so we can best treat patients in the future and also discover new methods of assessing response to treatment.

If you agree 4 separate 5 ml samples (a teaspoon each) of whole blood will be taken in the course of the regular BTOG2 hospital visits. One of these will be prior to receiving the BTOG2 study drugs, 2 during your first visit for chemotherapy and 1 further sample 7 days later when you return for your day 8 treatment. Your blood samples will be stored for future analysis of protein markers using the expertise within the Institute for Cancer Studies in Birmingham. The blood samples which we collect from you will be anonymised, which means that the researchers who are carrying out tests on your blood will not be able to trace it back to you.

This laboratory sub-study is not a compulsory part of the BTOG2 trial. If you do not want your blood to be used in this way please tell us on your consent form. You can still take part in the BTOG2 trial.

Your blood sample will not be sold to third parties or used for commercial gain. However, you should be aware that any new inventions that arise as a result of findings from this laboratory research may be protected so it can not be freely copied and used by others (known as intellectual property rights) and as such could be exploited commercially. The rights to any intellectual property will reside with the researchers.

Please note that the research tests used may develop during the time you are on treatment or in some cases years later, so we ask that you give approval for these tests to be performed using the blood samples without being contacted for permission on each test. It is unlikely that what we learn from these studies will have a direct benefit to you, but these studies may benefit patients in the future.

You may withdraw from this sub-study at any time without having to withdraw from the whole study, unless you wish to. You do not have to give any reason for your decision, and your standard of care will not be affected. If you withdraw consent from the study after your blood samples have been anonymised and coded they will continue to be used in the final analysis.

What if something goes wrong? If you are harmed by taking part in the BTOG2 study, there are no special compensation arrangements. If you are harmed due to someone’s negligence, then you may have grounds for legal action but you may have to pay for this. Regardless of this, if you wish to complain about

Patient Information 28/8/07 Version 5 Page 5 Cancer Research UK Clinical Trials Unit Birmingham any aspect of the way you have been approached or treated during the course of this study, the normal complaints procedure mechanisms may be available to you. Your doctor will give you further information if necessary.

Who is organising and funding the research? BTOG2 is a clinician-initiated and clinician-led study. The study is being organised and run by the BTOG2 Study Office at the . The running costs of the trial will be met by Cancer Research UK and funds secured through the British Thoracic Oncology Group (BTOG) and the NHS Cancer Research Network mechanism. Your doctor will not receive any personal financial payment for including you in the BTOG2 trial.

Are there alternative treatments? If you decide not to take part in this study, your doctor will discuss the options with you. This may include using other chemotherapy drugs or other methods to relieve some of your symptoms such as radiotherapy. Alternatively, you may choose not to have any treatment.

Will I be paid for taking part? You will not be compensated for taking part in this study.

What if I choose to leave the study? If you do choose to withdraw from the main BTOG2 study we would still like to collect information about your treatment as this will be invaluable to our research. If you have any objection to this please let your doctor know when you do decide to withdraw from the study. Data already collected prior to withdrawal will be kept and analysed.

Will my taking part in this study be kept confidential? All your details will be treated as confidential. Your doctor will give us your name and NHS number when s/he telephones to register you on the study and the BTOG2 Trial Office will collect a copy of your signed consent form to confirm you have read and understood this information . Other than this consent form, once you are randomised into the study all information about you which leaves the hospital will refer to you only by a unique trial number allocated to you, or by your initials to preserve your anonymity.

Occasionally we may need to check your medical records to make sure that the information provided about you was accurate. This will be done by clinical staff or designated Trials Unit personnel. A government body called the Medicines and Healthcare products Regulatory Agency (MHRA) may also require access to your medical records to ensure that the trial is being run in accordance with UK law. Under no circumstances will you be identified in any way in any report arising from the study.

After your treatment we will continue to contact your hospital to find out how you are. We know that it is possible for patients to lose touch with their hospital. If this happens we still need to be able to collect important basic details on how you are for the full duration of your life. The Office of National Statistics (ONS) keeps records that can easily provide the information we need. With your consent ONS will pass on this information to the BTOG2 Study Office if required. Any information received in this way remains confidential and is used only for the purpose of this trial only.

The results of these studies may be used for medical and scientific publications, but you will not be identified by name in any presentations or reports dealing with this research.

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With your consent your GP will be informed that you wish to take part in the study and your GPs address will be supplied to the BTOG2 Study Office. Your GP may be asked to provide information from your records which are required for the study.

What if I want more information? You will be given a copy of this information sheet and the signed copy of the consent form for you to keep. Please feel free to ask any further questions of the doctors and nurses looking after you before deciding to take part in the trial or at any time during the study. Before you make a decision, you may want to discuss the study with your family and friends and with your family doctor.

Doctor Telephone No:

Study Nurse Telephone No:

24 hour contact number:

The 24 hour contact number can be used out of working hours (9am – 5pm) in the event where you need to contact a hospital doctor immediately. If you prefer you can contact BACUP (an independent patient advisory group): Freephone: 0800 181199 Address BACUP: 3 Bath Place Rivington Street London EC2A 3JR Or visit their website at http://www.cancerbacup.org.uk.

Please take as much time as you need to make a decision and then let your doctor know what you have decided so that your treatment can be arranged.

Thank you for taking time to read this leaflet and considering taking part in this study.

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