Clinical trial: NCT00608972
Section: Participant's Rights
Subsections: Signaturn Ot Reaner/Tran$La"Toris Ht{ Patiint Dons Not Rea"D English|$Ignaturs O$' Inv Usti Ga'I'Or Oit Rnsponsitsln Individu Al

English well. I read"English *ell;nd arn flus,tt in . - ,.*. :*.: ,. , I language the patient  
  
understands well. I understand the content of this *onse* filnn and hnve translatsd for the patient the entire content of this forrn, 'l'o thc best of niy knowlcrlge, the patient undcrst*nds the content of this forur and has hacl un opf$rtunity to nsk questiuns reganling lhe consent lbml and thu sludy, and these questions have been answered.  
  
  
  
  
Title of Snuly: A Ph$se II Triul of Soxil , Curbnplutin llnd lleyminumah in Triplu N*gmiv* Pruvitusly l-htreated h{qtastatic l]rcnst  
Canc.er

To the best ol my ability, I have explained anil discussed the full contents oi'the study including all of the infurrnation containe$ in this consent t-orm. All qutstions of the patient have been eccurately answered  
| Nuuc: Signaturei   | Dute:   |
|--------------------|---------|
| Nams; Signature :  | Datc:   |  
$ignature:
and the patient h*s been given a copy ofthe consent.  
nvestri gaiorlPersott Obtai ning Cunsent :
Narne of Ir  
| Canc.er Rsoderl Translator: Witness:   |
|----------------------------------------|  
Duie:
Clinical trial: NCT00608972
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Tleasn Note; T}Iertr Is No Placebo (Inactive Druc, Or'(Sugar" Pill) Used In This $Tuay. All Patiants Wili, R.$Ceiy$ Acti"Iai, Drt]G.|Rare B|Lt Serious R Shortness Of Breath|Rare Bqt Seriouql|Rarr B*T $Prious;

I{hlt are thr risks rntl/or tli*comfsrts lf I chote to pnrticipatt in this etudy?  
Any risks listed may be serious enough to restilt in hospitaliz*tion and/or death'  
  
  
The followlng *re sido effects, whfuh msy oecur with the drug c$rboplr4nl Likeh{:
r l.owered nurnber of red blood cells. Red blood cel]s carry oxygsn to the organs in your body' A
lowered number of retl cells is known as anemia and can rnake you leel very tired and
$0rnctirl}es shtlrt ot' hreath.  
r Lowcred nurntrer of white blood ceils. White blood cells help to prevent infections' A lowEred numbrr of whiie blootl cells may makc it ea$isr fur you tCI g$t sn infection.  
r Lowered number of platelet cells. Platelet c*lls hetp your blood to clot. A lowerBd number of platelet cells may make it easier for you to bruise {"Black and blue" marks) sr bleed' r Nausea (a "nsick" feeling in your stomach).  
, Vomiting.  
r Weekness r A very tired &eling
[,rw L,iklv:
r Diarrher.  
" Constipation r Hair toss, not only llom your head, but also ftom your underarms, fhce, eyelashes and pubic
&rea" t o a a t a a I a a a I
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You may not lbel like eating.
lfumbniss, tingling, and/or pain in yorx'hands and feet. This is usually reverfsible.
Changps in your levels of sodium (solt) and potassium in your blood.
Mouth sorcs
Yellowing of, the eyes/skin
Dark urine
Changes in the amou$t of urine
Pnin/rednesdswelling at the injection sito
Skin rash
Itohing
Shortresr of brqath
\Yheczing
Allergic ieactions
Hearing problerns (e.g. ringing in the ears, hearing loss)

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Rnre:r Mouth ulcer$ or blisters r Blurred vision  
mn6vm ExPIHE$  
  
The folluwing art siek: clfucts, which nrny huppen with the drug {gll:
!=tkeh
. Nausea  
  
ocT ? t011 Fagc (r uf Nf  
  
  
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a a Asthsnia (fatigue, weaknffi$, tirednoss)
Anorexia (loss of aPPetite)
$ianlrea Constipction Neutropenia (fever)
Thromiocytopenia (abnormal drop in the number of blood cells involved in furming blood clots' Ibese cells are called Platelets)
r Anemia (below normal levels of rotl blood cells or henroglobin, or both, whiclt can be caused bY
many different conditions, including iron deficiency)
Rednesso pain, blistering of palms and soles of feet Hand-faot syndrome 6ffS;. Ir usually occur$ on the palms erf the hands and soles of the fbet' It can also occur on other parts of the borly where yow clothe$ miry be tight or where fiiction, pres$ure' rubbing, warmth, andlor sweating osc$r.  
Siomatitis, u mouth irritation characterize by inflanrnration or ulcers (sores)' Sorne common symptoms"o{ stomatitis include mouth $ores. clry swollen tonguc, dry crackcd lips, pain or buming in the mouth, inability to eat or drink, or tliffrculty swallowing.

n Tightness of chest and throst
. Erythema multiforme: a ra$h consisting of welts, somedmcs with purple or blistered are*s in the centar with itching, fcvero general ill tbeling r Srevens-Johnson iynaro*i: potentially deadty skin disease rrsulting in facial awelling, tongue swelling, hives, s*n pain, red or purple skin ro*h,. blisters on the skin, mu&o$s membranes
(especially mouth, nose e&d eyes), shedding af the skin
. io*i. epidermal necrolysis: u lif* thr*ut*ning skin di*ordsr that cau$ss blistering and pceling ofthe top layer of the skin  
Thr following are sid* effsctsn which rnay happon with tho elrug Bev*cizumsb (Avrstino):
Likely:
r Dinrrhea
. Nausea or the urge to vomit r Vomiting r Fatigue or tiredne*s  
  
a a I"ieadachc or head Pain lligh bloeid prsssure

r Damage of or clou in small blood vessels in rhe kidney thet ctrn ceuse complioations, sttnte of which are serious including abnonnal destruetion of red blood cells (hemotysis) or platelets (that help to clot blood) and kidney hilure
. Collection 6f signs and symptrrms th*t intlicate sutklen heart disea*e in which the heafi does not get enough oxygen. Sudden symptoms such as chest pain. shortness of breath- or t-ainting could inrJicate heafi disoase aucl should be rupoltrll riglrt away. liigns suclr as ut:rttonnul HKC arrd lrlood tests can eonfirn: damage to the heart.  
Heart failure : inability of trhe lreart t0 adequstely pump bloocl to supply oxygen to the body Decrease in heafl's abili$ ts pump bloo<l during the "astive" phnse of the heartbent (systole)
I"Ieart attaok cause by a blackage or decreascd blood supply to the hs&rt Inegular heartbeat resulting from an afrrormaliry in the one of tlre lower chambers of ths h6art (r'entricle)
Venticular librillation: irrcgular heartbeat that involves the low*r chamLrers ol'the heart {ventricles) that results in uncoeirdinate<I cnnlraction ol:tlre heart; life threalening ancl potentially fatal, ncedirtg inrmediale a 1)
t a t
*ttention
. Castrointestinul tissue r (iastrointestin*l perforation : A tear or lrole in the stomach (}r gut lhat cnlt le*cl to serious cornPlications and mry require $urgerY to rcPatr
. Sore (ulcer) somcwhsrs in tle digestive trect
. Serious, lifs+lrreatening allergic ieaction requiring irttmediate medisal trealrnsnt by your dostor' The reactiorl nray inrlude eKtremely low lrlood pi*.ur*, srvelling of the throut' cliff iculry brenthittg, and loss of consciousnes*.  
r Leakage from stomach due to breakdown of an anastomeisis {strrgical conneclion of two separate body strurturss)
Bleedirrg in lhe brain fistula: Abnormal hr:le bellr/eerl an orgall of tlro digestive tract attd attotlrer orgfrn or  
  
  
tikely: * Rddish urin{for
. Nausee
. Yorniting
. Mouth sores r Dehydr*tion
. Diarrh*n l-2 dsys)
. Signs ofcongestive heart fuilure {e.g., shortness cflhreath, ankle swolling)
r Fevsr
. $igns of infection r Pnin, burning or stinging at the injection site , Rever$ible aloPecia {hair loss)
. Low blood c*ti "ounL
(anemia,leukopenia, neutropenia, and thrombocytopnia)
. Fatigue r Temporary or permanent loss of men*trual cycle in womsn r Hot flsshes r Rash/itch

Epinrbicin causes *everal side effecrs, $ome of which can tre $evere. ln somc c8ses' epiruu'icin may need to be stopped beoausc ofthese side efF€ets.  
One of the most darrgerous ride effects of epirutricin i.s hetrt darnage' hr its most sevare form, this heart tlamagc manifests as congestive heart fhilure, rvhich can be futsl. Heart prublems can occur tnonths or y.urr-o{t*, slgpping epirubicirr. The prabaiilit,v ot'developing hcart failure is dependsnt on ths ffiffi;; ;;\#;iU;ti;;r;*ni*u is thq rotai amou*t o{'epiiubicin given aftu all chcmotherapv
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NPPNOV* EXPIRES  
  
irge l0 of 16 r Stroke caused by decroosed blood flow ts tlle brain r Abnormal chaflse$ in tlre hrain th*t can c&us6 s collection of symptoms including hcadacho, confusion'
**irur*u, md vifion loss associotsd with MRI inuging findings (RPLS)
r A condition in which the kidneys leak a targe alnount of protein into the urine th*l can cau$e complications inclutling swelling and kidney lailure
' Kidney failurc r Abnormal hole tretween part of the urinary systenl and anotlrer or&atl or ll$sue r Abnormal hole betrveen the vagina snd another organ or iis$ue r Abnormal hole betwpen the lower breathing tube *nd the boely cevity &at surrounds the lungs r Bleeding from the lungs
. Hole in the wall that separater the noskils of the nffie r Abnormal hale betwsen the bretthing tube (windpipe) end the lube th8{ gors liom mouth to stomach through which food pa$res (e.*ophagus). Thi* is life-lhreattr:ing and patentially fhtal' r Blockag* o, n*rro*ing erf a h1:od wssel (artery) rhat c{n cause danrage or loss of futtctiotr including a heart attack or stroke The following rro cide sfrecB, which may happen with th* rlrug &pirubicin:
*ose of S50rug/m2 and less than 39{ after a cllmulativs close ol'900 mg/m2. The risk of corye$tivc heert fbilure is a condition wher:s the heart does nut pump enough blood to support the nesds of the body.  
$econdary Leukemia has also been reportsd within three years of'stuppifig epirubicin' Based on several studies, the risk ofsecondary leukenria has been estirnated at ?% nffer eight years. Secondary leukemia is o cancer of the white blood cells in your bloocl thut fight irrtbctions that might be caured by treatrnent with epirubioin.  
gthqr risk$ $ssocitted lvith the studYr
, In "ddifis; to the known side effects listcd for three mcdirines ur*d in thix stutly' there ir slss thc posribility of tr n$il or u$onticipcted *ide effect when the thrce mcdieinos srt aombined together r There is the risk that this treetment may nelt work frrr ynu. . Side effests of having blood drawn liom a vein or lV {intravenous) t}rerapy: When your blood is drawn, there is u po.*ibility that there may bc a bruisc ("black and blue" rnark), bleeding or intbction
(rarely) at the place where the needle entered yotr vein.  
. Som. patients whu have an MRI moy dcvelop claustrophobia' lt is irnportant to let your doetor know if you have this problem. If you have a pacemaker or otlrcr metal object or device in your body or huo. rr*r worked with sheet metal you may not be able to have an MR[.  
. Some of the te$ts that wilt be performed on you (X-rays, C'[ scans, MRl, and/or bone scans, and MUGA scan [if requirert]) wilf expose you to cr:ntrolled amounts of radiation' The CT and/or MRI
scans and MTJCA u*** *ltt involve dyes being iniectcd into your vtin. l'here is a risk of allergic reaction to the dye, 'I'he injection oi suL,stances such as dyes into your blood may c'ause pain, srvelling, bruising, irritation or redness at the site" feel thint, or infbction at the site of the necdlc pun*t r". 't-l.re collection of tumor tissue sdds no additional risk to you since this tumr:r tissue was obtained frorn a preyicus biopsy. It is important that you report any side effbcts to your study dr:ctor
&s $oon as possible. You should nat wnit until your nexl scheduled visit.
Clinical trial: NCT00608972
Section: Procedures
Subsections: Therapy,|Asditional Rasearci{ Tbsting, }'Uturn Usb Tissua Samplss Orthe Ihtent T0 $T0Nm $Amfi,E$:

you must not breast feed a b*by rvbile taking part in this study und for 3 months after stopping ths study, b*cause the effects of this treatment nn a baby cannot be determined' lf you have any questions about birth congol, please spe*k to your study doetor' If you become pregnant, you *o*t immediately tell the study doctor, and you will stop stucly therapy' Are there any benefits if I chogse to participate in this resenreh *tudy?  
The benefit* of p"*i*ipnting in this stu<iy *uy b* thnt your cfllcer may shrink or stay the same sizs for a long period oftinre. l{owever, you mey r*c*iu" no clirect benelit tiom taking part in this study' ltrhrt ore my $tern*tives if I don't wrnt to prrticip,ttt ln this *tudy?  
yourfutor iswilling-io di**o*, the benefits and side.ff**t* of otherforms oftrsatmentsotherthamthis study that are avail*ble. These includs:  
r Other usual ehemtrtherupy for your type of cancer, rvhich may include tht same ffis of chernotherapy that is used on this study.  
r Otherexperimental studies with chemotherapy, hormones, radiation therapy, or new anti*cancer agent$ may be available for your disease.  
r you may also choose ns furthsr tre&tment, with care and mediqines to help you lbel more c.omfortsble.
please feel free to discuss these other options with your doctor and ask [lny questions you may have' Take as mueh time tl$ you nced to make your decision How will I knorry if ther* ls inl'ormation Imrnod thnt might affcct rny willingnese ta participate in this rcrerrch rtudy?  
During the course pf the sudy you rvill he updated abnut any new information that may affect your willinlress to remain in the study. If new inlormation is learned that may aflbct you afterthe study has completed, you will be contacted.  
who will have access to my research recortls from thlr study?  
By taking part in this study" you should understand that we will be cr:ltecting yow personal health inforrnation. This inoludes. but is ncrt limited to, ttenrographic elata (your name, date of birth, etc') ftnd clata on your healrh (your history, physical findings, laboratory resutts, study-related lindings, etc')'
Duri,g tir* .ouru* of iiris triat, stidy visitors (known as monitors) will revierv yuur nledical and rese*rch re*ord to make sure \&'e sollected your sturly information properly. These tnonitors are empl<lyed by The Cancer Institute of New Jersey. Sonretinms, they lvill *eed to take notLls or photCIcopy parls of your megical record. We will replaee your nan"le on these pagss with yuur assigned sttrdy nurnb$r' "l'his data wiil he reported to other staff at 'I'he Cancer lnstitute nf New Jersey on a regular basis, ns required by the stldy, The Cancer Institute ofNew Jerscy will an*lyzc! pnlcess. and storE your dota with electronic data processing systems" The authorizati$n ftr use of yortr research data has no expiratinn date' Your  
  
  
persoilal hedth infnrmation m&y be subjectredisclosin.c lry i,.Iu*unResearchServicesandifitisr,eelisclosed,itmayn0@ipersonalidentity, however, that is ygffi ngme, ucllress and other idenri{iers will remain cnnfidential (a stutly nurnher will be used for your name), Only the study doetor, research team arrd study monitor will be able to link the study number to your nflrne . Your tlata nray also be foruarded to domestic and foreign drug regulatory agencies if you have an adverse (bael) reacticln.  
The f.ollowing group$ of people nray also be allowed to inspcct sections r:f your medical and research records related to this studY:  
  
your intbrmation may also be subrnitted to domestic (within the United States) and lbreign drug regulatory agencies in applications ibr nrzu'kvting authori:r.ation arrd nray be used in scientific p,iUti".tlons fjournals. articlcs). If the iindings fiorn the study are publi*hed. you will not be identified Ly nu**. your itlentity will remain eonfidcntial unless thc larv requires us to give out this in{brmation, such as in the case r:l'r'ep*rling pcople wlto havc cliseascs otltcr; r;an catuh, ll this ctlli$, you will be infornred of the inlent tn di tion to the authodzed state agency. Such a law has already existed in you have the right to look at your per*onal infonnation at your study doctor's oflice end tu rcquest any conectiom of your personnl datg thst are wrong.  
Ifyou {o not cign this approval furmn you will nct be able to take part in this rEsearch stutly' lVill therc be nny cos(s ttt me to participntc in this studyl The drug Bevacizumab will be supplied ut n$ cotit to yuu your health insurance caricr nr rhird party payer will bc billed f-or the c.ost of rautine blood tests, x-Hrys, sgans and other routine tcsts thal would be part of your stttltdard rnedical care even ifyOu were not t*ting part in this study. Whale'i,er cosls yorr insurnnce cornp&ny does neit pay will be your
,*.poir*lbility. All cloctcri's or hospital cr"rsts will bc ch*rged tc you iu tltc same lvay as if you rvere not  
  
part clf this study.
Will I be paid to pnrticipat* in thie study?  
you will not be paid or receive any CIther forn of ccnrpen$etion to taks pert in this study' Whot will hrppen if I become injured during the sltrdy?  
If you participare in this stutly, youivill be cxpr:scrt tei certain risks ofphysical injury in addition to thr:se x*;;x*mi;;'.Hm:lffi ffi ;;[;;,ilf r;Tffi1'ilJ::l'l,i"ffit;ii'::$:;
as a direct con$equenc* orpa?i*ip*iiilTli,i* risearch. Your health insursnce carrier or other third party payor wilt be billetl for the cost of this treatment. No additional financial payment is available' you ure not giving up any of your legal rights by signing llris fomr or by participating in this research study.  
ill not provide paynrent for any nredical €xpense$, which you nray incur as a result of y n in this studY.  
What wig hlppen if I do not wish to p*rtiripate or dccide not to rontinue in the study?  
you may choose not to be in the study and if you clo choose toparticipate it is voluntnry' You may also ref,use to participate, or change your mind nt any time. lf you do not want lo snter thc study or decide to withdraw(stopiaking part) iron: the stncly, your relaticnship with the stucly staff will not change, and yo* may ct, ,o *itlJui penalty or loss ofbenefits to which you are otherwise entitled' lf ytlu do not w*nt us to conlinue usi already collested about you, you must withdraw your permission in writing Even if you withclraw our permission to use the data about you. we cannotretrieve ffi?fur* infomiation previously submitted. We are required by the
'pooA and Drug Administration however, to rontinue to report anything that relates to the safety of these drugs At any tims, the stutly doctur can decicle to withdraw you fiorn this study because tu take pan Further wouli not be in your best interesl. Your study cloctor cen stop trealment even if you are rvilling to continue. If you, or your study doctor, dccidc to rvithdraw you from the study you may be asked to retum fbr a final visii fr:r salety rca$ons.  
Also, you should unders{and fhat the stucly doc.tor can withdraw you {ium thc study at any tim* ifyou dc nst fuilow the instructions related ta the study, or if you need a different treatment.  
Who may I eontsci if I hsvt any que$tions?  
  
If you have any que$tion$ about your pcrticipation in this .sludy" ysu can oontact the ntudy doctor:

Pleasc initial each one of the following sentsnces that applies:
I agfee to be contacted by the tnvestigators tu*r firture research studies.  
I do not agree to be contactect by the Investigators fbr future research studies.  
I agrec to tha use CIf my bloo\#tissue fur future roseffch
,I do not agre t0 the use of rny bloodliissue for future resealch I understand that if I do not v{ant my sarnp}es used for future research it will not aflect my ability to take part in this study or in future studies.  
lryhat &r$ ury right* if I dccirle to pnrtieipato in this re*sareh *tudy?  
you have tle right to ask questions *on***ing any part of the study at any time. You slrould not sign this fomr unless you have had a chance to ask que*iions and receive &nswer$ to all of your questions' I have reacl this sntire form, or it has been read to *re, and I believs that I understand what has been discussed. All of rny questions regnrdiug this form or this study have been answeretl. I agree to perticipate in &is researsh study and have been given a copy of this consent' Patient Name:
Patient Signature: I)ntc:
Clinical trial: NCT00608972
Section: Voluntary Participation
Subsections: Conshi\It To Takp Part In A Rassarch Sti.'I}Y Concer Institute Of New Jer*Ey

A Phase II Trial ot'Doxil. Carboplatin and Bevacizumab in'l'riple Negntive Previr:usly untreated Metastatic Breast Cancer
'l'itle of Study:
Principtl lnvestigltor:
lntroduction This furrn is part of an informed consent procsss fur o reseflrch study and it will give infarmation that wi1 help yoo ro decide whether you wish to volunteer fbr this rcsearch study. It will help you t'o undErstand what the study is about and what will hoppen in the couse of the study' Ifyou have questions st any time during the research study, you shtruld teel tlee to ask them and should expect to be givcn answers that you cornpletely understand' After all of your questiono have becn answersd, if you still wirh to take psrt in the study' you will be asked ta sign this informed consent firnn.  
The str.rly doctor (the principal invcstigotor) or another msmber of the study team (an investigntor) will also be asked to sign thir i*th*ed conseni. You will be given a copy of the signed consent forn'l to keep.  
you arc not giving up eny of your legal rigfits by volunteering fur this research study r:r by signing thi* cnnsent forrn, Funding CompanY of StttdY
The doctor and/or Institution is the "sponsor-investigator" of this Study. This mea$s the doctor and/or Institutisn is the one who both initiatus zurd actually conducts, alone or with others, a study, that is" under whose immediare directi6n thc study drug is adrninistered, dispcnsed, or used'  
  
Titleof$tudy:Al'hnrcllTrialol'Dtlxil,Clarbpplulinandli*vacirumsbin lriple ),legati ve Il'eviorrsly l)ntrcated Metustatic Breasl Cancer A phannaceuiical comPanY,
being paid to coniluct this study according is * suppnrter CIf thi$ re$eerch study' Th* study doctor is to a butlgct. The budget covers some of the costs of il%J'- [I} 'If L'fix"'i*Y,'ffi ac i zum ah collecting the infl will be supplied bY
r\#hy have I bren rsked to partieipnte in this study?  
you are being askedto take pur in this study becauu* yrlo have metaststic {spreadto otherparts of the body) breast sancsr. ffris type of caneer is usually treated with drugs called'ochemotlrcrapt''(dnrgs used tokillcancercells),yourtypeofbreerst.un"*risnegativefbraproteincatledHER2/neu' Yourtypeof breast c.ancsr isqlso o*guti* for es*ogen r*"*ptorrlER) uncl piogesterone receptors (PR)' HER'2lneu' ER und pR are pafi of a family of rcceprurs fi:unrl on hoth cancer ancl normal cells. This family of receptors is inrportant for cell gto*L and is fbund in rnany tumor types' The body is made up of tiny building blo*ks called cells thal eontrol every body function. Some cells stop worki*g as thsy xhould
*nd booor,fre canserous cells. unlike healthy *lu*, "***r cells grow and multiply abnormally' destroying bcdy organs.  
The purpose of this research study is to look at the effectiveness of a s.onrhination of doxil' carboplatin and bevacizumab on m$isstatic breast cancer' This stldy is being conducted fnr the tglltlwing research purpss*s:  
r To fintl out what effects, if any, rhe study drug hus on yCIur cflncqr. For instance, will the study drug cause your tumor(s) to shrink or stop growing?  
r To test the safety of the snxly drugs and to ser: whnl alTee ts it has on you. For instance, nrc there any side effects? If so, what kintl of siae e&cis does the study drug cause? How severe are the side ellb*ts, and how ollen do theY occur?  
r To see if the study drugs have any effcct on keeping your diseass from getting worse'
r To mr:nitor your heaith and overall well-being rvhile taking the study drug, Doxil is used in the treatment of solicl tumors including breast cancer, bladder cancer, small cell lung s{mcer, thyroid c&ncer! gastric canccr} malignunt lympli,rtras of b'oth }Iodgkin &nd non-Hodgkin type, anrl auut.] lymphocytic. (lyrnphublastiu) leukemia' If thse is a shortage of doxil you will be *blc to receive tr$atment with epirubicin' a commercially available drug that is sirnilar to tloxil. Epirubicin has been appreived by the FDA for the treatment of breast cancer. You will qt.rntinur: :-au othqr srudy treatments and sat'ety monitoring ss outliDed in IFFffivAL ExPIRE$
this consent.  
  
  
l,itle of study: A ph*se II Trial {)f Derxil , cturboplutin ul}d l3evncizumab in Triple Negarive Prcviously untrealed Met&slttiu Brca$t Cmcer Principal lnYestigst$r Bevasizurnab is an antibndy direeted against vasculu endothelial growth factor, or VI:fiT. VH0F is a potent, specific growth factor with * *"ll-d*tined rolp in normrl and abnormal blood vessel formation.  
it i* pr.**rt in a wide variety of nonnal tissues, hut is prsduced in excess by most solid cancers
(tumors). In the setting of cancer, VEGIr promotes the growth of blood vessels that bring nukients to tr*rnor cells, ln studieJwith laboratory animals, trevacirumab inhibits the growth of several dilTersnt gpes of human cancer cells, inclurling colon cancer cr:lls, hy blocking thu elfeets of VHGF'
Bevacizumab rsceived o'accelcrnted" approval by the FDA fur the trsetmsfit of met&$tetic breastsancsr in 200g based on posirive e*rly findings from a large clinical trial that bevacieumab in combination delayed ths progressinn of breest cancei significantly longer than when chemotherapy r*as given alone' Final approval, htrwever, was contingen{ on two adrtitional stutlic$ in metastatic breast caneer demonstrating similar findings. Recent malysis of &e two trials did not show the sanre benefit noted in the original rtuay. Because oith* potential side elTects ass$cinted with the drug, nnd thE less signific*nt benEfit noted in the two conlinnatory studiss, the F'DA is cunsitlering withdrawing approval for the-treetment in breast canser. The FDA has encouraged, however, trials to determine populations of patients for whom th* elrug's benefits may cxceed ihe risks. Triple neg*tive brenst canser may be a sultype *f breust cancsr inlvhich the benefits outweigh tlre risks. Therefrrre, we da not know how the intbimation Jlorn the other stu{ies applies to you with advanced triple negative breast cancer' The FDA ha* approved carhoplatin for use in treating cvarian cflncer. Carhoplatin is al.so used ta treat various typ., oi'canc$r, tt is o chemotherapy drug that contains platinum. It is used alone or in combinaiion with other rnsdications to slow or stop cancsf cell growth'  
Who may or mey not partleipttc in this study?  
In order to take part in this study, you nrust lravc the following conrlititltts:
r you must be a woiltan with a diagnosis of metastatic breast cancer with none of the prtrtein HER2/nue or estrogen receptors ([tt) or prr:gesterone reseplors (PR) presenl.  
r You must be 2 l8 Years old,
. you must not havE received chemotherapy {drugs given to kill cancer cells) for mstastatic brenst clln0€r.  
r your cencer must bs able Io be measured, either by a physicsl examination or rcview of an x-ray' o You c&nnot be pregnant or nursing a baby while on tiiis srudy.  
. If you ane able to beco,rre pregrant and have a batry. you nlust have a pregnancy test that is negative (meaning you are not prBgnanl,t an<I agree to use el'fective birth eontrol, (e'g',
obitinence, intrauirlnc d*vice, nrul .ontr**eptives, barrier device with sperneicide or surgicnl strriliratiog) during trs*ltinent antl I'rlr three months afier conrpleting fieaturert.  
e your heart must bofunctioning normally. The study docior will son{irm this through standard tests u$ed to meaqure hean function.
How long will the *tutly take and how many patients will particip*tc?  
This study is estirnated tu enrull patients over two years. You will uontinue treatment until your disease worsens(prcgr-rffi 1"he study doctor  
  
lAppH$ffiff* fg IeCe lrv'l Title of Study: A phnse ll Trirl of $oxll , Corboplutin nnd Bcvneinrmsb in Triph }legative Pmviously Untraated Mctustalit llrsast C*ncer will decide if the treatment is n0 longer of benelit for you and if you should come offof the study' About 50 patients total are expeqg! ro rake part in this study, About l0 patients are sxpected tu take part in this studY at the r\#h*t witl I be fl$k€d to tlo lf I purtiuipnte in this rescnrch sturly?  
Beforc you may take part in this study, you rvill need to anslryer questions and have the following te$t$
and examinadCIns tCI see if you are eligible. This is called $crBsnin&, It is irnPortant thst you answsr illl que$tio$ honestly and eoinpletely, If anything changes bef"ore or during the study, you must tell th€
study doctor, Based upon the &n$wers to the*c-questiins and the rcsults of the tests and examinations which Save been performed there is a possibitrity thar ynu mey not qualify for participation in this study' ln some insta$ce$, certain t$sts or procedures conducled during the study rnay have to be repeated' For example, this can occur if *n,rr* o* all of tha results are unusahle' Also, you may be asked to have additional tests or examinations. For exarnple, this can r:rcour if an unexpeeted medical event occurs duri*g the study, Before you begin trsotmeni. you will need to have tire following tests and procedures done:  
I
t I
a
a t  
A history and PhYsieal exam' you will be asked about ths Extent of'your physical aotivity and how you are generally feeling" Your weight and height will be taken.  
you will have bloqrd ir*,,vn using a smoll needle or plastic tube, to check your blaod cell uounts, your blood chemistry, how yauiliver and kidneys are workipg ald your electrolytes' You will have a urine test to monitor the level of protein in your urine' You will have an sleusgardiogram {onc (also known as "[CG" or "CIKG")' This is a painle ss peprr tracing of your heart's normal eleotrical activity' you will huve a special heart test sallsd a MUCA silan" These tests will tell the doctors how well your heart works &s a pump. This is important, since some of the drugs used in this study rnay affect your hcart nluscle. 'fhis test will be repeated several tirnes during the study' A MUGA scan msa$l;Igs how well yr:ur heart pumps bloori' During the MUGA scan' a radioactive marker is i4iected into a vein- and special eq*ipment is used to measure the pumping caPacitY af Your heart.  
, (special tests which If your doctor feels you neetl it, you rnay have to h*ve a CA]'scan or MRI
looks at the organs in Your bodY).  
If you are able t0 become pregnant and have a h*by, you must have a I
wi'tfuin one wEek ot'enrollment. "l'he results of this test must be negadve pregl}ency test taksn  
  
In addition during the study, you will have:
. Blor;d tests bslbre trcetment and weckly during the srudy. A complete blood count (CBC) will be checked weekly to make $ure y$u have safe ievels of the differeut types of blood cells in your body'andtrrsechowthctrcatmcl)tcftbctsatypcufblotW
m-J;, 0[T ? 20fi  
  
iififfilfif,\ r"'** + *,"  
  
  
r Other bisod tests including chen:istries and effects frorn the trealmellt. You rvill have a liver {iu:ction test$ rvill he d*ne to check fi:r side urine test belbre treatment to mottiteir the level of pnrtein in your rlrine.  
A CA'Iscan (computed axial imaging) or anMRtr (Magnetic Resonance Imaging) may he done eyery S weeks whilr you ff* on thi study if the study doctor {bels it is needed. T}:e CAT scan or MRI will be dona to look st the size *nd location (place) of tumors.  
you will also need to have an ECG ($lectrognrdiogram, also known as an "[KG" * a painless paper tftruing of the heart's nunnal electrical activity)'
you will have a Ml,$A ssan every l2 weeks and one month alter your last treatment with the study drug combinntion'
The treatmont rchedule l* ss followu lf you decide to take part in this study and are able to join based on ths abovo criterin, you will hnve the following treahrent.  
you will have the clemother*py (drugs used to kill cancer cells) with the drugs doxil, carboplatin and bevacir..umab. A geatm*ot p*iin,t *itt t* 28 days long. This period is known as fl oncyclen'' All medications are given using a small needle or plastic tube into one of your veins' carboplatin snd doxil will be given on Day I of e*ch 28 day cycle.  
Bevacizumab will be given on Day I after you have received carboplatin and doxil' Bevacizumab will also be givsn by itsslf on D*y 15 of each 28 day cycle.  
| r                                         | 12-14      | 15    | t 6-?8   |
|-------------------------------------------|------------|-------|----------|
| X                                         | I No drugs | No    | drugs    |
| X -*l                                     | given      | given |          |
| doxil trevaeieumab                        | X          | X     |          |
| X = dnrg is taken ,L:"+"y"r * carboplatin |            |       |          |  
You will continue to receive these medicati*ns unless:
o You have ssvere, ssrious and/or excEssive side effects' r Your cfilcer becomes worse. r You wish to stop taking part in this stutly.  
r Your tluctor &sls it is not in your best interest to eontinue this trettment"