SAMPLE INFORMED CONSENT A Phase I Study f CEP-701 in Patients with Refractry Neurblastma NANT (01-03) A New Appraches t Neurblastma Therapy (NANT) treatment prtcl. The wrd yu used thrughut this dcument refers t yu r yur child. WHAT IS THIS STUDY ABOUT? This study is a clinical trial (a type f research study using human patients). Clinical trials include nly patients wh chse t take part. Please take yur time t make yur decisin. Discuss yur decisin with yur friends and family. Yu are being asked t participate in this study because yu have been diagnsed with neurblastma, a type f slid cancer that usually affects children. Yur cancer has either relapsed r yu have persistent tumr after having gtten standard treatment. Standard treatment may have included chemtherapy, surgery, radiatin therapy and/r high-dse chemtherapy with a stem cell transplant. WHY IS THIS STUDY BEING DONE? The purpses f this study are: T find the highest dse f CEP-701 that can be given twice a day Mnday thrugh Friday withut causing severe side effects. T find ut the side effects seen with giving CEP-701 n this schedule at different dse levels. T measure bld levels f CEP-701 during treatment and t see if the drug at these levels can kill neurblastma cells in a test tube r in yur bne marrw. T determine if yur tumr gets smaller after treatment with CEP-701. The research is being dne because: Currently there is n knwn effective treatment fr yur type f cancer. CEP-701 is an anticancer drug that wrks differently than standard chemtherapy medicines. It blcks signals that helps the neurblastma cancer cells t live and grw. These signals are taken int the cell thrugh prteins called Trks fund n surface f mst neurblastma cancer cell. CEP-701 blcks these signals in lab studies. CEP-701 has been given safely t adults with different cancers. It may have helped sme leukemia patients, but there has been n shrinkage f adult slid cancers studied s far. The majr side effects seen have been nausea, vmiting, diarrhea, cnstipatin, lss f appetite and feeling weak. This is first study f CEP-701 in children. HOW MANY PEOPLE WILL TAKE PART IN THIS STUDY? Between 30-60 peple will take part in this study.
WHAT WILL HAPPEN TO ME ON THIS STUDY AND WHAT IS INVOLVED? If yu agree t be n this study, we will ask yu t d the fllwing things. CEP-701 is taken by muth twice a day with r after breakfast and dinner fr 5 days (Mnday thrugh Friday) fllwed by 2 days f rest (Saturday and Sunday) when n drug is taken. This is repeated 4 times fr a ttal f 28 days fr ne curse f treatment. The drug cmes as a liquid and shuld be mixed with juice. We will teach yu hw t give the drug. Dse escalatin f CEP-701 Yu will nly receive ne dse f CEP-701. Fr the whle study, we will analyze each dse in 3-6 patients at a time. The starting dse fr the first grup f patients is abut 25% lwer than what is currently being given t adult patients withut bad side effects. The dse f CEP-701 will be increased ( dse escalatin ) in grups f 3-6 patients until side effects are seen. At this pint investigatrs will have fund the highest dse f CEP-701 that can be given twice a day Mnday - Friday withut bad side effects. We will tell yu what dse yu will receive and answer yur questins abut dse escalatin. Yu will have a series f standard medical tests befre, during and fllwing treatment with CEP- 701. Researchers will use these tests t measure the effectiveness f the treatment and what it is ding t yur bdy. MEDICAL TESTS BEFORE AND DURING TREATMENT -Physical exam -Bne marrw tests # -Bld tests -Varius scans* -Pregnancy test -Test f heart functin (befre starting treatment nly) -Urine tests # Bne marrw tests are dne by inserting a needle int the hip bne t remve the marrw which is inside the bne. * VARIOUS SCANS THAT ARE DONE FOR DIAGNOSIS AND CHECKING THE RESPONSE OF THE TUMOR TO TREATMENT. THESE MAY INCLUDE CT AND /OR MRI SCANS AND MIBG SCANS. WE WILL RECOMMEND SCANS SPECIFIC FOR YOUR CASE AND WE WILL ANSWER YOUR QUESTIONS ABOUT THESE SCANS. The chart at the end f this frm tells yu when these tests need t be dne. Medical Tests Fllwing Treatment -Physical exam -Bld tests -Bne marrw tests -Urine tests -Varius scans -Test f heart functin In additin t the rutine studies listed abve that are required t mnitr yur prgress during treatment, we wuld like t perfrm additinal studies such as pharmackinetic (bld level) studies and tumr bilgy studies while yu are enrlled n this prtcl. Each f these special studies is described in the sectins belw. Althugh these studies are very imprtant t imprving ur understanding f this new drug, the results f these studies will nt directly influence yur treatment. Yu may chse nt t participate in the pharmackinetic and bilgy studies and will still be eligible t receive the experimental treatment. The results f these studies will nt affect yur treatment while enrlled n this study and the study results will nt be tld t
yu r yur dctr and will nt becme part f yur medical recrd. The investigatrs will use the samples t study hw yur bdy uses the medicatin and if the medicatin has any effect n the tumr cells. There are checkbxes n the next t last page f this cnsent frm t mark whether yu are willing t participate in these vluntary studies. Determining Bld Levels f CEP-701 (called Pharmackinetics) Part f the research gal fr this study is t lk at the level f CEP-701 in the bld. A little mre than half a teaspn f bld (3ml) will be drawn frm a vein (by intravenus r central line) at 12 different times n first day yu start treatment with CEP-701. On this day yu will nly take the mrning dse f drug. The first sample is taken befre taking the dse f CEP-701, then several times fr the first 8 hurs after yu take the drug, and then 24 hurs after taking the drug. Tw mre samples will be drawn n day 5 and 26 befre yu take the mrning dse f CEP-701. This can all be dne in the utpatient clinic. This part f the study is vluntary. Deciding nt t take part in this part f the study will nt affect yur verall care r yur ability t get CEP-701 as part f this clinical trial. Bilgy Studies dne fr Research Purpses Anther research gal fr this study is t find ut if CEP-701 in yur bld can kill neurblastma cells. This infrmatin will help researchers t understand if CEP-701 still might be wrking even if yur tumr des nt shrink. Bld Study. This testing requires taking 2 extra teaspns f bld 3 times n days 1, 5 and 26 f treatment. The results f these tests will be cnfidential and will nt be made available t yu r yur treating physician as they are experimental and will nt be used t determine therapy. This part f the study invlving bld tests n days 1, 5, and 26 is vluntary. Deciding nt t take part in this part f the study will nt affect yur verall care r yur ability t get CEP-701 as part f this clinical trial. HOW LONG WILL I BE ON THIS STUDY? Yu can cntinue t get treatment every 28 days fr as lng as yur neurblastma respnse t the treatment r yu d nt have bad side effects frm taking CEP-701. After yu stp treatment with CEP-701, yu will cntinue t have tests and scans dne t measure hw much tumr is left. Yur dctr will tell yu hw ften these tests will be dne. Researchers will cntinue t cllect infrmatin abut yu fr a lifetime. Infrmatin will be cllected abut whether yu are still alive, whether yur tumr has grwn back and at what sites in the bdy; whether yu have develped any side effects frm the treatment r any additinal cancer. This infrmatin may be gtten frm yur nclgist r family dctr at regular intervals. Yu can remve yurself frm this study at any time.
WHAT ARE THE RISKS OF THE STUDY? The majr risks are related t the experimental drug CEP-701. Side effects seen FREQUENTLY in adult patients: Nausea Diarrhea Lss f appetite and nt feeling like eating Overall feelings f bdy weakness Cnstipatin Vmiting Side effects seen RARELY in adult patients: Feelings f indigestin, stmach upset Lw bld pressure Bleeding frm the gut Heart failure Side effects seen FREQUENTLY in children: Nausea Diarrhea Lss f appetite and nt feeling like eating Cnstipatin Vmiting Liver irritatin/increased liver functin tests. Other drugs may be given t make side effects less serius and mre cmfrtable. Many side effects g away shrtly after the treatment is stpped, but in sme cases, side effects may be lng lasting r permanent. Sme side effects may be life threatening and it is pssible that death culd ccur as a rare side effect fllwing treatment with CEP-701. Patients are watched carefully and treatment will be stpped if bad side effects develp. Because this drug has never been given t children befre, there may be risks we d nt knw abut. Because this drug can affect an unbrn baby, patients f child-bearing age shuld nt becme pregnant r father a baby while n this study. Ask abut cunseling and mre infrmatin abut preventing pregnancy. The risks frm having yur bld taken are minimal but can result in a infectin r a bld clt. Experienced dctrs r nurses will perfrm these bld draws t minimize this risk. Bne marrw tests als can lead t infectin, and they ften require that yu get sedatin (sleep) medicines. Bne marrw tests may cause pain during the prcedure r bleeding at the site n yur hip where the test was dne. These have risks that will be discusses with yu. Yu will sign separate cnsent fr any prcedure that needs sedatin. WILL I BENEFIT FROM THIS STUDY? There may r may nt be direct medical benefit t yu. The infrmatin learned frm this study may r may nt benefit ther children r yung peple with slid cancers in the future.
ARE THERE OTHER TREATMENT OPTIONS? Yes there are ther ptins fr treatment. Instead f being in this study, yu have these ptins: Treatment with chemtherapy medicines. Treatment with ther experimental agents that may be available. N therapy at this time with care t help yu feel mre cmfrtable. Please talk abut these ptins with yur dctr. WILL MY RECORDS BE CONFIDENTIAL? Yu may read yur recrd. The recrds are available t thse peple caring fr yu at this hspital. Hwever, all effrts will be made t keep yur infrmatin cnfidential. Unfrtunately, we cannt guarantee abslute cnfidentiality. Infrmatin abut yu may be shared if required by law. Organizatins that may lk at and/r cpy yur (yur child's) research recrds fr quality assurance and data analysis include such grups as: New Appraches T Neurblastma Therapy (NANT) Cnsrtium at Childrens Hspital Ls Angeles in Ls Angeles, CA. The NANT Cnsrtium identifies yu (yur child) by a number. Independent auditr evaluating quality assurance fr the NANT Cnsrtium The Federal Gvernment Natinal Cancer Institute (NCI) and the Fd and Drug Administratin (FDA) may examine recrds f patients participating in this study. Cephaln Inc., the cmpany supplying CEP-701 fr this study. WILL I HAVE TO PAY FOR THIS TREATMENT? Cephaln, Inc. will prvide CEP-701 free f charge fr this study. If during the study CEP-701 becmes cmmercially available, yu may have t pay fr the amunt f drug needed t cmplete the study. Taking part in this study may lead t added csts that may be cvered by yur insurance cmpany. Please ask abut any expected added csts r insurance prblems. In case f illness r injury resulting frm this study, emergency medical treatment is available but will be prvided at the usual charge. N funds have been set aside t cmpensate yu in the event f an injury. Yu and/r yur insurance cmpany will be charged fr cntinuing medical care r hspitalizatin. Yu will receive n payment fr taking part in this study. Yu may have t pay fr ther things during this study, such as but nt limited t, yur time, the cst f fd yu buy while yu are being treated at the hspital, car fare, parking, and baby sitter fees.
WHAT ARE MY (MY CHILD S) RIGHTS AS A STUDY PARTICIPANT? Taking part in this study is vluntary. Yu may chse nt t take part in this study. If yu participate, yu may remve yurself frm the study at any time. If yu remve yurself frm the study, we will still take care f yu. We will explain what stpping the treatment may d and we will ffer ther treatments if they are available. Yu will nt be penalized r lse any regular benefits. Yu als have the right t knw abut new infrmatin that may affect yur health, welfare, r willingness t stay in the study. We will give yu this infrmatin. WHOM DO I CALL IF I HAVE QUESTIONS OR PROBLEMS? Fr questins abut the study r an injury related t the research, please call NAME at TELEPHONE NUMBER Fr questins abut yur (yur child's) rights as a study participant, please call NAME OF INSTITUTIONAL REVIEW BOARD REPRESENTATIVE # NAME at TELEPHONE NUMBER # The Institutinal Review Bard is a grup f peple wh review the research study t prtect yur rights. WHERE CAN I GET MORE INFORMATION? Yu may call the NCI s Cancer Infrmatin Service at 1 800 4 CANCER (1 800 422 6237) r TTY: 1 800 332 8615 Visit the NCI s Web sites Cancer Trials: cmprehensive clinical trials infrmatin http://cancertrials.nci.nih.gv. Cancer Net : accurate cancer infrmatin including PDQ http://cancernet.nci.nih.gv. -Yu will get a cpy f this cnsent frm. -Yu may als ask fr a cpy f the prtcl (full study plan).
Cnsent fr Extra Studies fr Research Bld Levels f CEP-701 (Pharmackinetics) #1 Circle YES, if yu agree t let researchers take a little mre than half a teaspn f bld (3ml) 12 times n the first day f treatment with CEP-701 and 1 mre sample each n day 5 and day 26 f treatment (ttal 14 samples) t lk at the level f CEP-701 in the bld. These are extra bld draws. The results f these tests will be cnfidential and nt made available t yu r yur treating physician. Circle NO, if yu d nt want researchers t take 14 extra bld samples t lk CEP-701 levels in the bld. #1 YES NO Signature Participant: : Bld fr Tumr Bilgy Studies #2 Circle YES if yu agree t let researchers take an extra 2 teaspns f bld 3 times n day 1, 5 and 26 f curse ne t lk at activity f Trk B in the bld. This testing wuld require 3 extra bld draws n days 1, 5 and 26. The results f these tests will be cnfidential and nt made available t yu r yur treating physician. Circle NO if yu d nt want researchers t take an extra tw teaspns f bld 3 times fr bld studies abut Trk B activity. #2: YES NO Signature Participant: :
STATEMENT OF CONSENT I have already read the infrmatin in this infrmed cnsent dcument. I have read all the attachments that were included with this infrmed cnsent dcument. I have asked all f my questins and I have gtten answers. I agree t enrll myself (my child) in this study. Patient Name Signature f Parent r Guardian / / Signature f Parent r Guardian / / Signature f Patient (If > 7 years ld) / / Signature f Physician r Respnsible Investigatr Signature f Witness / / / / Signature f Translatr (If applicable) / /
STUDY Cnsent Addendum: Tests that will be dne n this study. Befre Study During Curse 1 End f Curse 1 During Curse 2 Physical Exam X X X X X Bld tests X Weekly X Every ther week End f Curse 2, 4 and Off Prtcl Rx Pregnancy test X - X - X Urine test X - - - - Heart test (ECHO) X - - X (ff Prt. Rx) Tumr imaging (CT/MRI & X - X - X MIBG scan) Bilateral bne marrw aspirate/bipsy Bne marrw fr immuncytlgy X - X (nly if + at start f study) X - X (nly if + at start f study) X - X (nly if + at start f study) - X (nly if + at start f study) Urine test (VMA/HVA) X - X - X CEP-701 bld levels - X (nly if cnsent given) - - - Bld bilgy studies - Day 5 (nly if cnsent given) - - -