| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Stage IV unresectable, recurrent or metastatic
non-squamous non-small cell lung cancer (nsNSCLC) |
| Stadij IV inoperabilnog, povratnog ili metastatskog karcinoma pluća ne-pločastih nemalih stanica (nsNSCLC) |
|
| E.1.1.1 | Medical condition in easily understood language |
| A certain common kind of inoperable, recurrent or metastatic Lung cancer. |
| Određena uobičajena vrsta inoperabilnog, rekurentnog ili metastatskog raka pluća. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10025055 |
| E.1.2 | Term | Lung cancer non-small cell stage IV |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| Compare the overall response rate (ORR) of MYL-1402O with that of Avastin, in combination with CP chemotherapy during the first 18 weeks of first-line treatment in patients with Stage IV nsNSCLC |
| Usporediti ukupnu stopu odgovora (ORR) MYL-1402O sa stopom Avastina, u kombinaciji s KP kemoterapijom tijekom prvih 18 tjedana liječenja prvom linijom u bolesnika sa nsNSCLC faze IV. |
|
| E.2.2 | Secondary objectives of the trial |
1. Assess the safety profile of MYL-1402O as compared with that of Avastin when administered in combination with CP as
first-line treatment for Stage IV nsNSCLC and when administered alone in the maintenance setting
2. Assess other efficacy parameters: Disease Control Rate (DCR), Duration of Response (DR), Time To Progression (TP), Progression-Free survival (PFS), and Overall Survival (OS) of
MYL-1402O as compared to Avastin when administered in
combination with CP as first-line treatment for Stage IV
nsNSCLC
3. Assess the potential immunogenicity at Week 18 and 42 of
treatment of MYL-1402O as compared with that of Avastin
4. Compare the pharmacokinetic (PK) profile of MYL-1402O and Avastin using a population PK (PopPK) approach |
1.Procijeniti sigurnosni profil MYL-1402O u usporedbi s profilom Avastina kada se primjenjuje u kombinaciji s KP kao liječenje prve linije za stadij IV nsNSCLC i kada se primjenjuje sam u terapiji održavanja
2. Procijeniti druge parametre učinkovitosti: stopu kontrole bolesti (SKB), trajanje odgovora (TO), vrijeme do progresije (VP), preživljenje bez progresije bolesti (PBPB) i ukupno preživljenje (UP)
MYL-1402O u usporedbi s Avastinom nakon primjene kombinacija s KP kao liječenje prve linije za Stadij IV nsNSCLC
3. Procijeniti potencijalnu imunogenost u 18. i 42. tjednu liječenja MYL-1402O u usporedbi s Avastinom
4. Usporediti farmakokinetički (PK) profil MYL-1402O i Avastina pomoću populacijskog PK (PopPK) pristupa |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Has demonstrated the ability to understand verbal and/or written instructions, to provide written informed consent, and is capable and agreeable to comply with protocol requirements.
2. Male or female at least 18 years of age at the time of signing an informed consent form.
3. Has a documented imaging diagnosis of Stage IV unresectable, recurrent or metastatic nsNSCLC.
4. Has a documented histologic or cytologic diagnosis of advanced nsNSCLC with negative or unknown sensitizing epidermal growth factor receptor (EGFR) mutation, and negative or unknown echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangement.
5. Has measurable disease with at least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors
(RECIST 1.1; Section 12.1 [Appendix A]). All target (up to
5 lesions) and nontarget lesions (other measurable not included in target, nonmeasurable, nonevaluable, or evaluable lesions) should be included in the assessment or evaluation of disease response as defined by RECIST 1.1 (Eisenhauer et al 2009).
6. Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group scale.
7. Has at least 6 months of expected survival.
8. Has not received any prior systemic therapy for first-line treatment of advanced lung cancer, except adjuvant chemotherapy, and remained disease-free for at least 12 months from time
9. May have had prior radiation therapy provided <25% of bone marrow is involved (Section 12.3 [Appendix C]), except for previous mediastinal irradiation that is not allowed.
a. Prior radiation therapy must have been completed at least
2 weeks prior to Day 0 of Cycle 1
b. Patient must have recovered from acute toxicities associated with radiation therapy. Radiation-related toxicities must have resolved to Grade 1 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE; version 4.03) grade prior to Day 0 of Cycle 1.
10. May have brain metastasis provided the metastasis has been treated and is considered stable at the time of signing the informed consent form. Treated, stable brain metastasis is defined as:
a. Metastasis having no evidence of progressive disease (PD) or hemorrhage after treatment.
b. No ongoing requirement for dexamethasone, as ascertained by clinical examination and post-treatment brain imaging (computed tomography [CT] scan or magnetic resonance imaging [MRI]) at baseline.
c. Anticonvulsants are allowed, provided the dose regimen has been unchanged (stable) for at least 2 weeks prior to patient signing informed consent.
d. Treatment for brain metastasis may include whole brain
radiotherapy, radiosurgery (Gamma Knife®, linear particle
accelerator, or equivalent), or a combination thereof, as
deemed appropriate by the treating physician. All brain
metastasis treatments must be completed at least 14 days prior to Day 0 of Cycle 1.
11. Has adequate organ functions based on the following:
a. Bone marrow reserve:
i. White blood cell count ≥3 × 103/μL;
ii. Absolute neutrophil count (segmented and bands)
≥1.5 × 103/μL;
iii. Platelet count ≥100 × 103/μL;
iv. Hemoglobin ≥9.0 g/dL with at least 2 weeks without
transfusions before Day 0 of Cycle 1.
b. Hepatic:
i. Total bilirubin ≤1.5 × upper limit of normal (ULN); except
if elevation is due to Gilbert’s Syndrome with transitory
elevations of indirect bilirubin.
ii. Alkaline phosphatase, alanine transaminase, and/or
aspartate transaminase ≤3 × ULN. Significant levels of
alanine transaminase or aspartate transaminase should be
further assessed for viral hepatitis. (Note: Isolated alkaline
phosphatase elevation beyond 3 × ULN due to bone
metastasis is allowed).
c. Renal:
i. Calculated creatinine clearance ≥45 mL/min based on the
original, weight-based Cockcroft and Gault formula
(Cockcroft and Gault 1976; Section 12.4 [Appendix D])
ii. Urine protein via dipstick: 0 or 1. Patients ≥2+ can be included only ifa 24H urine specimen yields <2g of protein.
12. If capable of reproduction, patients and their partners must use contraceptive methods during the full duration of the study and for 6 months after discontinuation of study.
A patient who is capable of reproduction must be willing to
practice birth control by using 2 different highly effective double barrier methods of contraception, or abstinence from sexual intercourse for the duration of the study.
In particular a female patient of childbearing potential must use a method that results in less than 1% failure rate per year when used consistently and correctly such as implants, injectables, combined oral contraceptives, intrauterine devices, sexual abstinence, or vasectomized partner.
A male patient of reproductive potential (defined as a male that has not had a vasectomy) must use a condom with spermicide and their female partner to use another highly effective form of contraception. |
1.Pokazao je da može razumjeti usmene i/ili pisane upute, dati informirani pisani pristanak te da je sposoban i spreman na poštivanje zahtjeva plana ispitivanja.
2.Muškarac ili žena star/a 18 godina ili više u trenutku potpisivanja informiranog pristanka.
3.Ima snimkom dokumentiranu dijagnozu inoperabilnog, rekurentnog ili metastatskog nsNSCLC-a stadija IV.
4.Ima dokumentiranu histološku ili citološku dijagnozu uznapredovalog nsNSCLC-a s negativnom ili nepoznatom senzibilizirajućom mutacijom receptora EGFR i negativnom ili nepoznatom translokacijom EML4-ALK.
5.Ima mjerljivu bolest s barem jednom mjerljivom lezijom prema definiciji RECIST 1.1; Odjeljak 12.1. [Dodatak A]. Sve ciljne (do 5 lezija) i neciljne lezije treba uključiti u procjenu ili ocjenu odgovora bolesti prema definiciji sustava RECIST 1.1 (Eisenhauer i dr. 2009.).
NAPOMENA: Ako se kod faza procjena otkriju metastaze kostiju i lokaliziraju izvan prsnog koša i abdominalne regije, svaku neciljanu metastazu ili višestruku neciljanu metastazu kostiju treba uvrstiti u procjene tumorskog odgovora i popratiti rendgenom, CT snimanjem ili MR-om, prema situaciji.
6.Ima funkcionalno stanje od 0 ili 1 na ljestvici ECOG.
7.Ima očekivano preživljenje od barem 6 mjeseci.
8.Nije prethodno primao nikakvu sustavnu terapiju za prvu liniju liječenja uznapredovalog karcinoma pluća, osim adjuvantne kemoterapije te je ostao bez bolesti barem 12 mjeseci od trenutka operacije i barem 6 mjeseci od posljednje doze KT.
9.Mogao je prethodno proći terapiju zračenjem pod uvjetom da je uključeno <25% koštane srži (Odjeljak 12.3 [Dodatak C]), osim prethodnog medijastinalnog zračenja koje nije prihvatljivo.
a.Terapiju zračenjem završio je barem 2 tjedna prije 0-tog dana 1. ciklusa.
b.Ispitanik se oporavio od akutnih toksičnosti povezanih s terapijom zračenjem. Toksičnosti povezane sa zračenjem moraju pasti na 1. stupanj prema ljestvici CTCAE, inačica 4.03, prije 0-tog dana 1. ciklusa.
10.Može imati metastazu u mozgu, pod uvjetom da je metastaza liječena i da se smatra stabilnom.
Liječena, stabilna metastaza u mozgu definira se kao:
a.Metastaza koja ne upućuje na progresiju bolesti ili krvarenje nakon liječenja.
b.Nema trajne potrebe za deksametazonom, što potvrđuju klinički pregled i snimke mozga CT-om ili MR-om nakon liječenja prilikom utvrđivanja početnih vrijednosti.
c.Antikonvulzivi su dozvoljeni, pod uvjetom da je režim doziranja stabilan barem 2 tjedna prije nego što je ispitanik potpisao informirani pristanak.
d.Liječenje metastaze u mozgu može uključivati radioth. cijelog mozga, radiokirurgiju (Gamma Knife®, linearni akcelerator čestica ili ekvivalentnu metodu) ili kombinaciju navedenog, ovisno o tome što nadležni liječnik smatra prikladnim. Sva liječenja metastaza u mozgu moraju biti završena barem 14 dana prije 0-tog dana 1. ciklusa.
11.Ima odgovarajuće funkcije organa na temelju sljedećeg:
a.Pričuve koštane srži:
i.Broj leukocita u krvi ≥3 × 103/μL;
ii.Apsolutni broj neutrofila (segmentiranih i nesegmentiranih) ≥1,5 × 103/μL;
iii.Broj trombocita ≥100 × 103/μL;
iv.Hemoglobin ≥9,0 g/dL, s time da ispitanik najmanje 2 tjedna prije 0-tog dana 1. ciklusa nije primao transfuziju.
b.Jetreni:
i.Ukupni bilirubin ≤1,5 × gornja granica normale, osim ako su povišene vrijednosti prouzročene Gilbertovim sy. s prolaznim povišenim vrijednostima bilirubina.
ii.ALP, ALT i/ili AST ≤3 × ULN. Visoke razine alanin transaminaze ili aspartat transaminaze treba dodatno provjeriti u odnosu na virusni hepatitis, ako nisu povezane s metastazama jetre. (Napomena: dozvoljeno je izolirano povišenje alkalne fosfataze iznad 3 × ULN zbog metastaze u kostima).
c.Bubrežni:
i.Klirens kreatinina ≥45 mL/min izračunat jednadžbom Cockcrofta i Gaulta koja se temelji na težini (Cockcroft i Gault 1976.; Odjeljak 12.4. [Dodatak D]).
ii.Proteini u urinu (testnim štapićem): 0 ili 1. Ispitanici s ≥ 2+ mogu mogu se uključiti samo ako uzorak urina prikupljenog tijekom 24 sata sadrži <2 g proteina.
12.Ako su reproduktivno sposobni, ispitanici i njihovi partneri moraju primjenjivati kontracepcijska sredstva tijekom cijelog trajanja ispitivanja i 6 mjeseci nakon prekida sudjelovanja u ispitivanju.
Reproduktivno sposoban ispitanik mora biti spreman na zaštitu od začeća primjenom dviju različitih, visoko učinkovitih metoda kontracepcije dvostruke barijere ili na suzdržavanje od spolnog odnosa tijekom trajanja ispitivanja.
Ispitanice reproduktivne dobi naročito moraju primjenjivati metodu koja rezultira stopom neuspjele zaštite manjom od 1% godišnje ako se koristi dosljedno i ispravno, na primjer, implantate, injekcije, kombiniranu oralnu kontracepciju, intrauterine uloške, suzdržavanje od spolnih odnosa ili partner koji je podvrgnut vazektomiji.
Reproduktivno sposobni ispitanici (muškarci koji nisu vazektomirani) moraju upotrebljavati prezervative sa spermicidom, a njihove partnerice moraju primjenjivati dodatni visoko učinkovit oblik kontracepcije. |
|
| E.4 | Principal exclusion criteria |
1. Is pregnant or breast-feeding.
2. Has documented histology/cytology confirming any of the
following:
a. Squamous non-small cell lung cancer. (Note: In the event of mixed tumor histology/cytology or predominant cell type other than non-squamous, eligibility will be determined based on the predominant cell type, which must be non-squamous.)
b. A patient with any small cell type or large cell neuroendocrine histology.
3. Has a recent (within 6 months prior to Day 0 of Cycle 1) cardiac condition as defined by the New York Heart Association Class II, III, or IV (AHA 1994).
4. Has a recent (within 6 months prior to Day 0 of Cycle 1) history of a significant vascular event (such as aortic aneurysm requiring surgical repair or a recent peripheral arterial thrombosis) and/or history of significant and unstable vascular disease.
5. Has a history of stroke or transient ischemic attack within
6 months prior to Day 0 of Cycle 1, or has a long-term history of more than one of the following vascular thromboembolic events:
a. Cerebrovascular accidents
b. Transient ischemic attacks
c. Myocardial infarctions
d. Venous thromboembolic reactions, including pulmonary
embolism
6. Is receiving anticoagulant therapy that:
a. Is not considered ‘stable’, defined as dosage not maintained
for at least 3 months prior to Day 0 of Cycle 1.
b. Is not within the targeted international normalized ratio at the time of consent signing.
7. Has a current diagnosis, history, or risk of hemorrhage in the central nervous system (CNS), including the following:
a. Patient with CNS metastasis treated by neurosurgical resection or brain biopsy performed within 8 weeks prior to Day 0 of Cycle 1.
b. Patient should be off corticosteroids for at least 1 week
(7 days) at the time of the post-treatment (for CNS metastasis) brain CT/MRI.
8. Has any prior history of hypertensive crisis and/or
hypertensive encephalopathy, or has a current diagnosis or
recent history of inadequately controlled hypertension (defined as systolic blood pressure >150 mm Hg and/or diastolic >100 mm Hg, while on antihypertensive medications).
9. Has a recent history of any of the following:
a. A major surgical procedure, open biopsy, open pleurodesis, or significant traumatic injury within 28 days prior to Day 0 of Cycle 1.
b. Documented history of conditions that may need surgery
during the study or within 6 months of signing informed
consent.
c. Has had either a core biopsy or other minor surgical procedure within 7 days prior to Day 0 of Cycle 1. (Note: Placement of a vascular access device, or a closed pleurodesis, thoracentesis, or mediastinoscopy are allowed).
10. Has a history of any of the following:
a. Hemoptysis (approximately >2.5 mL or a half teaspoon)
within 3 months prior to Day 0 of Cycle 1.
b. A thoracic, central, mediastinal tumor location in contact with major vessels
c. A cavitated lung tumor. See more details in protocol.
11. Has a history of gastrointestinal fistula, perforation, or abscess.
12. Has a current diagnosis or history of a nonhealing wound, active ulcer, or untreated bone fracture.
13. Has prior history of another active malignancy within the last 5 years, other than adequately treated superficial basal cell, superficial/skin squamous cell carcinoma, or carcinomas in situ.
14. Has a known hypersensitivity to any component of carboplatin, paclitaxel, bevacizumab, Chinese hamster ovary cell products, or other recombinant human or humanized antibodies.
15. Has received treatment with any other investigational drug, prior to day 0 of cycle 1, within the last 30 days or 5 half lives (if available); whichever is longer.
16. Has previously received treatment with the following:
a. Paclitaxel.
b. Bevacizumab (Note: Prior intravitreal administration of
bevacizumab does not preclude study participation).
c. Anthracycline. (Note: May be allowed on a case by case basis after consulting with the medical monitor to rule out an
increased risk of cardiac failure).
17. Has documented or known current alcohol/drug abuse that precludes his/her ability to adhere to the protocol.
18. Has any of the following concomitant treatments or conditions:
a. Concomitant vaccination that contains an attenuated virus, for instance Yellow Fever vaccine.
b. Has a known history of active or latent tuberculosis.
c. Has a concomitant systemic disorder (e.g., active infection
including known human immunodeficiency virus, viral
hepatitis B or C) that, in the opinion of the principal
investigator (PI; or designee), would compromise the patient's safety (for instance potential drug interactions, or ability to adhere to the protocol).
d. Has any other concomitant condition that precludes the
participation in the study through increased risk to the patient and/or potential to impact the PI’s (or designee’s) ability to administer this protocol. |
1.Ispitanica je trudna ili doji.
2.Dokumentirana histologija/citologija koja potvrđuje bilo što od slijedećeg
a.Karcinom pluća ne-malih pločastih stanica.
b.Ispitanik s histologijom karcinoma bilo koje vrste malih stanica ili neuroendokrinog karcinoma velikih stanica.
3.Ispitaniku je nedavno (unutar 6 mjeseci prije 0-tog dana 1. ciklusa) dijagnosticirana srčana bolest klase II., III. ili IV. prema NYHA (AHA 1994.).
4.Ispitanik je nedavno (unutar 6 mjeseci prije 0-tog dana 1. ciklusa) imao značajan krvožilni događaj (kao što je aneurizma aorte koju je bilo potrebno kirurški obraditi ili nedavna tromboza periferne arterije) i/ili povijest značajne i nestabilne krvožilne bolesti.
5.Ima povijest moždanog udara ili prolaznog ishemijskog napada unutar 6 mjeseci prije 0-tog dana 1. ciklusa ili ima dugotrajnu povijest više od jednog od sljedećih krvožilnih tromboembolijskih događaja:
a.Cerebrovaskularni inzult
b.Prolazni ishemijski napad
c.Infarkt miokarda
d.Venske tromboembolijske reakcije, uključujući plućnu emboliju
6.Prima antikoagulacijsku terapiju koja:
a.Se ne smatra 'stabilnom', odnosno u dozi koja nije održana barem 3 mjeseca prije 0-tog dana 1. ciklusa.
b.Nije unutar ciljanog INR u trenutku potpisivanja pristanka.
7.Trenutačno ima dijagnozu, povijest ili rizik od krvarenja u SŽS, uključujući:
a.Ispitanici s metastazom u SŽS-u liječenu neurokirurškom resekcijom ili biopsijom mozga provedenom unutar 8 tjedana prije 0-tog dana 1. ciklusa.
b.Ispitanici bi morali biti slobodni od kortikosteroida barem 1 tjedan (7 dana) u vrijeme snimanja mozga CT-om/MR-om nakon liječenja (za metastaze na SŽS-u).
8.Ima bilo kakvu prethodnu povijest hipertenzivne krize i/ili HT encefalopatije ili ima trenutačnu dijagnozu ili nedavnu povijest neadekvatno kontrolirane HT (sistolički >150 mm Hg i/ili dijastolički >100 mm Hg, uz uzimanje lijekova protiv HT).
9.Ima nedavnu povijest bilo čega od sljedećeg:
a.Veliki kirurški zahvat, otvorena biopsija, otvorena pleurodeza ili značajna traumatska ozljeda unutar 28 dana prije 0-tog dana 1. ciklusa.
b.Dokumentirana povijest stanja koja mogu zahtijevati kiruršku obradu tijekom ispitivanja ili u roku od 6 mjeseci od potpisivanja informiranog pristanka.
c.Bio je podvrgnut kor-biopsiji ili drugom manjem kirurškom zahvatu unutar 7 dana prije 0-tog dana 1. ciklusa.
10.Ima povijest bilo kojeg od sljedećeg:
a.Hemoptiza (približno >2,5 mL) unutar 3 mjeseca prije 0-tog dana 1. ciklusa.
b.Tumor u prsištu, centralno, medijastinalno , smješten unutar 2cm od grebena, koji prodire u ili potiskuje velike krvne žile i povezani rizik od krvarenja prema prosudbi GI.
c.Tumor pluća s kavitacijom, ako je kavitiralo više od 50% promjera lezije, i/ili je zahvaćen središnji bronhij ili žila.
- Velike krvne žile definirane su na sljedeći način:
•aorta
•gornja i donja šuplja vena
•glavna plućna arterija
•intraperikardijalni dijelovi desne i lijeve plućne arterije i plućnih vena
- Središnja lokacija definira se kao:
• udaljenost od manje ili jednako 2 cm od grebena
EC 10 će se procijeniti od slučaja do slučaja, uzimajući u obzir navedene kriterije u razgovoru s radiologom u centru, GI i MM.
11.Ima povijest GI fistule, perforacije ili apscesa.
12.Ima trenutačnu Dg. ili povijest rane koja ne zacjeljuje, aktivnog ulkusa ili neliječenog prijeloma kosti.
13.Ima prethodnu povijest druge aktivne malignosti unutar proteklih 5 godina, osim adekvatno liječenog površinskog Ca bazalnih stanica, površinskog/kožnog Ca pločastih stanica ili Ca in situ.
14.Ima poznatu preosjetljivost na bilo koji sastojak karboplatina, paklitaksela, bevacizumaba, produkata jajnih stanica kineskog hrčka ili na druga rekombinantna humana ili humanizirana antitijela.
15.Primao je terapiju bilo kojim drugim ispitivanim lijekom prije 0. dana 1- ciklusa, unutar posljednjih 30 dana ili 5 poluvremena; što god je duže
16.Prethodno je primao liječenje sljedećim:
a.Paklitaksel.
b.Bevacizumab.
c.Antraciklin.
17.Ima dokumentiranu ili poznatu trenutačnu ovisnost o alkoholu/drogama koja isključuje njegovu sposobnost poštivanja plana ispitivanja.
18.Ima bilo koju od sljedećih usporednih terapija ili stanja:
a.Usporedno cijepljenje koje sadrži oslabljeni virus, na primjer cjepivo za žutu groznicu.
b. Ima poznatu povijest aktivne ili latentne tuberkuloze.
c. Ima usporedni sustavni poremećaj (npr. aktivna infekcija uključujući poznati virus humane imunodeficijencije, virusni hepatitis B ili C) koji bi, prema mišljenju glavnog ispitivača (GI; ili njegovog zamjenika), ugrozio sigurnost ispitanika (na primjer, potencijalne interakcije lijekova ili mogućnost praćenja plana ispitivanja).
d. Ima bilo koje drugo usporedno stanje koje isključuje sudjelovanje u ispitivanju zbog povećanog rizika za ispitanika i/ili mogućnosti utjecanja na sposobnost glavnog ispitivača (ili njegovog zamjenika) da provodi plan ispitivanja.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint is the ORR |
| Primarna završna točka učinkovitosti je ukupna stopa odgovora |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| During first 18 weeks |
| Tijekom prvih 18 tjedana |
|
| E.5.2 | Secondary end point(s) |
Efficacy Endpoints:
· DCR (CR, PR, or stable disease)
· PFS
· OS
· DR
· TP
PK Endpoints:
PopPK measures of exposure of MYL-1402O and the reference product Avastin (e.g., AUC, Cmax, Cmin, CL, Vc, and the terminal elimination half-life).
Safety Endpoints:
· Incidence, nature, and severity of AEs including adverse drug reactions graded according to CTCAE.
· Detection of antibodies to bevacizumab. |
Krajnje točke učinkovitosti:
· DCR (CR, PR ili stabilna bolest)
· PFS
· OS
· DR
· TP
PK krajnje točke:
PopPK mjere izloženosti MYL-1402O i referentnog lijeka Avastina (npr. AUC, Cmax, Cmin, CL, Vc i poluživot terminalne eliminacije).
Krajnje točke sigurnosti:
· Učestalost, priroda i težina nuspojava, uključujući nuspojave koje se ocjenjuju prema CTCAE.
· Otkrivanje protutijela na bevacizumab. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Endpoints will be assessed during the entire duration of the study in line with the protocol schedule of events.
|
| Krajnje točke procjenjivat će se tijekom cijelog trajanja ispitivanja u skladu s rasporedom događaja navedenim u Planu ispitivanja. |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 50 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Belarus |
| Bosnia and Herzegovina |
| Bulgaria |
| Croatia |
| Georgia |
| Hungary |
| India |
| Italy |
| Poland |
| Romania |
| Russian Federation |
| Spain |
| Taiwan |
| Turkey |
| Ukraine |
| Vietnam |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| “Study closure will occur when either all patients have discontinued the study, or 42 weeks from the date the last patient was randomized to treatment OR at the administrative closure of the study. Patients on treatment at study closure will be advised by the PI and/or their associated primary health care provider on alternate therapies as per standard for the country. All treatment provided under the auspices of this protocol will cease at study closure.” |
"Zatvaranje ispitivanja će se dogoditi kada su ili svi pacijenti prekinuli studiju ili 42 tjedna od datuma kada je posljednji bolesnik randomiziran na liječenje ILI na administrativnom zatvaranju ispitivanja. Bolesnici na liječenju na zatvaranju ispitivanja će biti obaviješteni od strane PI i / ili njihovog pružatelja primarne zdr.zaštite o mogućem liječenju prema standardu za zemlju. Svo liječenjekoja se pruža pod okriljem ovog plana ispitivanja prestaje nakon završetka ispitivanja. "
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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