Clinical Trials Register

Summary
EudraCT Number:	2013-003324-36
Sponsor's Protocol Code Number:	NT14035-3/2013
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-09-11
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Czechia - SUKL

A.2

EudraCT number

2013-003324-36

A.3

Full title of the trial

Kinetically guided removal of plazma pegylated liposomal doxorubicin to enhance the benefit of cytostatic therapy of patients with ovarian cancer.

Kineticky řízené odstranění plazmatického pegylovaného liposomálního doxorubicinu ke zvýšení benefitu cytostatické léčby karcinomu ovarií.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

The removal of plazma pegylated liposomal doxorubicin for the benefit of cytostatic therapy of patients with ovarian cancer.

Odstranění plazmatického pegylovaného liposomálního doxorubicinu ke zvýšení benefitu cytostatické léčby karcinomu ovarií.

A.3.2

Name or abbreviated title of the trial where available

The removal of plazma pegylated liposomal doxorubicin for the benefit of therapy.

Odstranění plazmatického pegylovaného liposomálního doxorubicinu ke zvýšení benefitu léčby.

A.4.1

Sponsor's protocol code number

NT14035-3/2013

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Charles University in Prague, Faculty of Medicine in Hradec Králové
B.1.3.4	Country	Czech Republic
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Charles University in Prague, Faculty of Medicine in Hradec Králové
B.4.2	Country	Czech Republic
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Department of Oncology and Radiotherapy, Charles University in Prague, University Hospital in Hradec Králové
B.5.2	Functional name of contact point	Stanislav Filip
B.5.3	Address:
B.5.3.1	Street Address	Sokolská 548
B.5.3.2	Town/ city	Hradec Králové
B.5.3.3	Post code	50005
B.5.3.4	Country	Czech Republic
B.5.4	Telephone number	+420495834618
B.5.6	E-mail	filip@fnhk.cz

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Caelyx
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag International NV
D.2.1.2	Country which granted the Marketing Authorisation	Czech Republic
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	CAELYX CARTON 20 mg/10 ml
D.3.2	Product code	EU/1/96/011/001
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Primary aim: enhanced therapeutic benefit of liposomal doxorubicin - a drug indicated for ovarian cancer resistant to chemotherapy with the first line drugs. This approach can be considered a model study for another formulation of liposomal drugs useful for cancer chemotherapy.

Primární cíl: Zvýšení terapeutického benefitu liposomálního doxorubicinu – cytostatika indikovaného pro ovariální karcinom rezistentní na léčbu cytostatiky první volby. Tato studie může sloužit jako modelová k výzkumu zvýšeného benefitu u dalších liposomálních cytostatik.

E.1.1.1

Medical condition in easily understood language

The aim is enhanced therapeutic benefit of liposomal doxorubicin - a drug indicated for ovarian cancer resistant to chemotherapy with the first line drugs.

Cílem je zýšení terapeutického benefitu liposomálního doxorubicinu – cytostatika indikovaného pro ovariální karcinom rezistentní na léčbu cytostatiky první volby.

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The objective to be solved in this project is the issue of circulation of nanotechnologically modified anticancer drugs in the time when they have no effect and may be the source of adverse side-effects and thus influence significantly both the treatment efficacy and „benefit cost“. After Cmax is achieved in the tumour tissue further circulation of liposomal cytostatic drug is not effective. Plasma level leads only to the development of adverse efects but with no effect. With a suitable extracorporeal elimination system it is possible markedly limit acute toxic effects of chemotherapy. For the therapy with rheohemapheresis we suggest to use pegylated liposomal doxorubicine in female patients with ovarian cancer. Newly, we wish to monitore still unexplored changes of hematologic, immunologic and metabolic parameters. The proposed project is in consistence with the program of the Ministry of Health, Czech Republic - 03. Oncology.

Předmětem řešení projektu je problém cirkulace nanotechnologicky upravených protinádorových léků v období, kdy již nejsou účinná a mohou být zdrojem vedlejších nežádoucích projevů, které významně ovlivňují jak efektivitu léčby, tak „benefit cost“. Po dosažení Cmax v nádorové tkáni je další cirkulace liposomálního cytostatika neúčinná. Plazmatická hladina vede jen k vzniku nežádoucích vedlejších efektů (zejména zažívacího traktu a kůže), ale nemá léčebný efekt. Vhodným extrakorporálním eliminačním systémem je možno výrazně omezit akutní toxické účinky chemoterapie. Takovou léčbu pomocí rheohemaferézy (kaskádové filtrace, která je považována za nejvhodnější eliminační systém pro tuto potřebu) navrhujeme při léčbě pacientek s karcinomem ovarií pegylovaným liposomálním doxorubicinem.

E.2.2

Secondary objectives of the trial

Secondary aim: identification of pathologic factors (covariates), that might significantly modify the liposomal doxorubicin kinetics and therapeutic effectiveness of such chemotherapy (age, progression of tumours with hepatic metastases,and others).
The project is compatible with principles and priorities of Resort program RPV III. chapter 7. 03, confined to oncology.
Priority: “Combination of molecular-directed therapy with classical approach (chemotherapy)“ and Contributions: “Improved medical care of patients suffering from cancers“.

Sekundární cíl: vytipovat faktory (kovariáty), které se významně promítají do kinetiky i účinnosti chemoterapie liposomálním doxorubicinem.
Svým obsahem projekt naplňuje základní cíle a priority Resortního programu RPV III. kapitola 7. 03, věnované onkologii.
Priority: „Kombinace molekulárně-cílené léčby s klasickými postupy (chemoterapií)“ a Přínosy: „Zlepšení výsledku péče o nemocné s nádory“.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Criteria for inclusion: 1 / Histologically confirmed epithelial ovarian cancer, fallopian tube or peritoneal carcinoma, 2 / Previous chemotherapy containing platinum and paclitaxel with the rise of resistance to chemotherapy; 3/Progression of disease (clinical findings, imaging techniques - CT, PET-CT MR elevation of tumor marker CA125) 4 / Age 18 years 5 / Performance status ≤ 1, 6 / Life expectancy 12 weeks, 7 / Adequate hematopoietic, hepatic and renal function; 8 / Signed informed consent.

Kriteria k přijetí do studie a kritéria vylučující:
Kritéria pro zařazení: 1/ Histologicky potvrzený epiteliální karcinom ovaria, vejcovodu nebo peritoneální karcinom; 2/ Předchozí chemoterapie obsahující platinu a paklitaxel s nárustem rezistence na podávanou chemoterapii; 3/Potvrzená progrese onemocnění (klinický nález, zobrazovací metódy - CT, PET- CT, MR; elevace nádorového markeru CA125); 4/ Věk 18 let; 5/ Performance status ≤ 1; 6/ Life expectancy 12 týdnů; 7/ Adekvátní hematopoetické, jaterní a ledvinné funkce; 8/ Podepsaný informovaný souhlas.

E.4

Principal exclusion criteria

Criteria for exclusion: 1 / Pregnancy and lactation, 2 / Allergy to doxorubicin and other anthracyclines, 3 / Severe cardiac disease (arrhythmia, cardiac insufficiency, status post myocardial infarction), 4 / Prior treatment with anthracyclines up to the maximum cumulative dose (550mg / m2), 5 / significant persistent myelosuppression induced by previous treatment with cytotoxic agents, 6 / Generalized infection 7 / Severe impairment of liver function.

Kritéria pro vyřazení: 1/ Gravidita a kojení; 2/ Alergie na doxorubicin a jiné antracykliny; 3/ Závažné srdeční onemocnění (arytmie, kardiální insuficience, stav po infarktu myokardu); 4/ Předchozí léčba antracykliny až do jejich maximální kumulativní dávky (550mg/m2); 5/ Výrazná přetrvávající myelosuprese vyvolaná předchozí léčbou cytotoxickými látkami; 6/ Generalizovaná infekce; 7/ Závažná porucha jaterních funkcí.

E.5 End points

E.5.1

Primary end point(s)

Estimation of individual doxorubicin kinetics (cycle 1): to determine doxorubicin plasma concentration after the first doxorubicin i.v. dose, 2 ml will be taken from a venous blood. In respect to both the clearance of doxorubicin and RHP, the first postinfusion sample will be drawn at 30 min after the termination of the first infusion. Additional samples will be taken at 44, 46, 72 a 150 postinfusion hours. Doxorubicin plasma concentration will be used for estimation of individual kinetic parameters: the systemic clearance, and AUC (area under the curve of doxorubicin plasma concentration in time after the start of infusion ). These data will be compared with those obtained in the literature. A slow rate of doxorubicin clearance and high exposure to the drug estimated after the first infusion would indicate the need of a higher rate of RHP or its prolongation after dose 2-4 within cycle 2-4 in order to achieve equipotent scheduled removal of the liposomal doxorubicin administered dose. Evaluation of data obtained from 40 cycles and correlation of individual doxorubicin kinetic parameters with both RHP effectiveness, and tolerability related to chemotherapy with liposomal doxorubicin is expected to generate instructions how to guide kinetically apheretic procedures.

Odhad individuální kinetiky doxorubicinu (cyklus 1): Před první dávkou cytostatika a po jejím dokončení odebrat 2 ml krve v následujících intervalech: 30 min, 44, 46, 72 a 150 hod po skončení infúze. Odběry realizovat z jiné žíly, než té, která sloužila k podávání léčiva. Z plazmatických koncentrací budou vypočteny individuální kinetické parametry doxorubicinu: plazmatická clearance a AUC (plocha pod køivkou) a porovnány s literárními údaji. Pomalá rychlost clearance a vysoká exposice doxorubicinu (AUC) zjištěná v cyklu 1, bude vyžadovat rychlejší ev. prodlouženou RHF v cyklu 2-4 tak, aby byla odstraněna doporučená frakce z podané dávky (přibližně 60%) v ekvipotentní podobě. Vyhodnocení 40 cyklů a korelace výsledků individuální kinetiky s účinností RHF a také s indikátory účinnosti a tolerability chemoterapie liposomálním doxorubicinem vyústí v doporučení, jak RHF kineticky řídit.

E.5.1.1

Timepoint(s) of evaluation of this end point

In the years 2013 - 2014: patients will be planned to be enrolled in respect to eligibility criteria, cyclus 1-4 and 2015: the termination of data collection and final evaluation including that based on statistical methodology

E.5.2

Secondary end point(s)

Clinical and pathological response to therapy. Patients will be followed during therapy and for 1 year after the completion of therapy (follow-up period) using physical examination, ultrasonography, RTG, computed tomographic (CT) scanning CT and /or MR), tumor biomarker titration (CA 125) and residual illness evaluation graded according to WHO classification - remission (no sign of tumor progression), partial remission (50% decrease in tumour size), tumour persistence (no change). TNM classification will be used as well (Sobin and Witekind, 1997).

Klinická a patologická odpověď na léčbu - účinnost (follow-up) po dobu 1 roku. Metody monitorování: zobrazovacími metodami (UZ, Rtg, CT ev. MRI), vyšetřením tu markerů CA 125, hodnocením reziduální nemoci podle stupnice WHO - remise (o 100%), parciální remise (zmenšení tumoru o 50%), perzistence (beze změny). TNM klasifikace bude rovněž využita (Sobin a Witekind, 1997).

E.5.2.1

Timepoint(s) of evaluation of this end point

V roce 2013 - 2014: zařazení pacientů indikovaných k chemoterapii, cyklus 1-4, sběr dat a průběžné hodnocení výsledků, prezentace výsledků na tuzemských i zahraničních kongresech, v recenzovaných domácích odborných časopisech. 2015: dokončení sběru dat a jejich finální statistické zpracování, publikace výsledků v mezinárodních odborných impaktovaných časopisech.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

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

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Dispensarization of patients after treatment.

Dispenzarizace nemocných po léčbě.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2013-10-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-11-07

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-01-30

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials