Clinical Trials Register

Summary
EudraCT Number:	2014-005251-39
Sponsor's Protocol Code Number:	PM1183-C-004-14
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-01-21
Trial results	View 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

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2014-005251-39

A.3

Full title of the trial

Phase III Randomized Clinical Trial of Lurbinectedin (PM01183) versus Pegylated Liposomal Doxorubicin or Topotecan in Patients with Platinumresistant Ovarian Cancer (CORAIL Trial)

Studio clinico randomizzato di fase III su lurbinectedina (PM01183) rispetto a doxorubicina liposomiale pegilata o topotecano in pazienti con carcinoma ovarico platino-resistente (studio CORAIL)

A.3.1

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

Phase III Randomized Clinical Trial of Lurbinectedin (PM01183) versus Pegylated Liposomal Doxorubicin or Topotecan in Patients with Platinumresistant Ovarian Cancer (CORAIL Trial)

Studio clinico randomizzato di fase III su lurbinectedina (PM01183) rispetto a doxorubicina liposomiale pegilata o topotecano in pazienti con carcinoma ovarico platino-resistente (studio CORAIL)

A.3.2

Name or abbreviated title of the trial where available

CORAIL Trial

Studio CORAIL

A.4.1

Sponsor's protocol code number

PM1183-C-004-14

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	PHARMA MAR, S.A. SOCIEDAD UNIPERSONAL
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Pharma Mar S.A., Sociedad Unipersonal
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Pharma Mar, S.A.
B.5.2	Functional name of contact point	Clinical Trials
B.5.3	Address:
B.5.3.1	Street Address	Av. de los Reyes, 1. Pol. Ind. "La Mina"
B.5.3.2	Town/ city	Colmenar Viejo, Madrid
B.5.3.3	Post code	28770
B.5.3.4	Country	Spain
B.5.4	Telephone number	0034918466077
B.5.5	Fax number	0034918466003
B.5.6	E-mail	cmfernandez@pharmamar.com

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	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/12/1053
D.3 Description of the IMP
D.3.1	Product name	Lurbinectedin
D.3.2	Product code	[PM01183]
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LURBINECTEDIN
D.3.9.1	CAS number	497871-47-3
D.3.9.2	Current sponsor code	PM01183
D.3.9.3	Other descriptive name	LURBINECTEDIN
D.3.9.4	EV Substance Code	SUB31196
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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 2 mg/ml concentrato per soluzione per infusione
D.2.1.1.2	Name of the Marketing Authorisation holder	JANSSEN-CILAG INTERNATIONAL N.V.
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
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	doxorubicin
D.3.2	Product code	[doxorubicin]
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DOXORUBICIN
D.3.9.2	Current sponsor code	DOXORUBICIN
D.3.9.3	Other descriptive name	PEGYLATED LIPOSOMAL DOXORUBICIN
D.3.9.4	EV Substance Code	SUB33393
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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.IMP: 3
D.1.2 and D.1.3	IMP Role	Comparator
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.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	topotecan hydrochloride
D.3.2	Product code	[NA]
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TOPOTECAN
D.3.9.1	CAS number	123948-87-8
D.3.9.2	Current sponsor code	TOPOTECAN
D.3.9.3	Other descriptive name	TOPOTECAN
D.3.9.4	EV Substance Code	SUB11191MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	4
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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

Platinum-resistant ovarian cancer

carcinoma ovarico platino-resistente

E.1.1.1

Medical condition in easily understood language

ovarian cancer

carcinoma ovarico

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	PT
E.1.2	Classification code	10033128
E.1.2	Term	Ovarian cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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	10033130
E.1.2	Term	Ovarian cancer NOS
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To determine a difference in progression-free-survival (PFS) between
lurbinectedin (PM01183) and pegylated liposomal doxorubicin (PLD) or
topotecan in platinum-resistant ovarian cancer patients according to the
Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1.

Determinare una differenza nella sopravvivenza libera da progressione (PFS) tra lurbinectedina (PM01183) e doxorubicina liposomiale pegilata (PLD) o topotecan in pazienti con carcinoma ovarico platino-resistente in base ai Criteri di valutazione della risposta nei tumori solidi (RECIST) v.1.1.

E.2.2

Secondary objectives of the trial

To evaluate:
- Overall survival (OS).
- Antitumor activity.
- Safety profile.
- Patient-reported outcomes (PRO).
To characterize the plasma pharmacokinetics (PK) of PM01183 using a
sparse sampling scheme in the PM01183 treatment arm (Arm A).
Subgroup analyses of the PM01183 arm versus PLD or topotecan.
To conduct an exploratory pharmacogenetic and pharmacogenomic
(PGx) sub-study.

Valutare:
• La sopravvivenza globale (OS).
• L'attività antitumorale.
• Il profilo di sicurezza.
• I risultati riportati dalla paziente (PRO).
Caratterizzare la farmacocinetica (PK) di PM01183 nel plasma utilizzando uno schema di campionamento ridotto nel braccio di trattamento con PM01183 (Braccio A).
Analisi del sottogruppo del braccio con PM01183 rispetto a PLD o topotecan.
Condurre un sottostudio farmacogenetico e farmacogenomico (PGx) esplorativo.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Pharmacogenetics
Version: NA
Date: 04/12/2014
Title: Pharmacogenetic evaluation
Objectives: To explore factors that may help to explain individual variability in main pharmacokinetic (PK) parameters,
the presence or absence of germline mutations or polymorphisms will be
analyzed in leukocyte DNA extracted from a blood sample obtained before treatment start in the PM01183 arm (Arm A).

Pharmacogenomics
Version: NA
Date: 04/12/2014
Title: PHARMACOGENOMIC EVALUATIONS
Objectives: The analysis of potential predictive factors to PM01183 treatment will be analyzed on prior available paraffin-embedded tumor tissue samples from consenting patients.

Other types of substudies
Specify title, date and version of each substudy with relative objectives: PHARMACOKINETIC EVALUATIONS - will be collected in all patients enrolled in the PM01183 arm (Arm A). The samples will be obtained in two cycles (in Cycle 1 and in a second cycle between Cycle 2 and 4). The selection of the second cycle with sample collection for the measurement of PM01183 will be assigned once the patient is randomized into Arm A.

Farmacogenetica
Versione: NA
Data: 04/12/2014
Titolo: Valutazioni Farmacogenetiche -
Obiettivi: Al fine di esplorare i fattori che possono aiutare a spiegare la variabilità individuale dei principali parametri di farmacocinetica (PK), verrà analizzata la presenza o assenza di mutazioni o polimorfismi germline nel DNA dei leucociti estratto da un campione di sangue prelevato prima dell'inizio del trattamento nel braccio con PM01183 (Braccio A).

Farmacogenomica
Versione: NA
Data: 04/12/2014
Titolo: Valutazioni Farmacogenomiche
Obiettivi: L'analisi dei potenziali fattori predittivi per il trattamento con PM01183 sarà eseguita su campioni di tessuto tumorale paraffinato precedentemente forniti da pazienti che hanno dato il proprio consenso.

Altre tipologie di sottostudi
specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: Valutazione Farmacocinetica: Valutazioni Farmacocinetiche - Saranno raccolti dei campioni da tutte le pazienti arruolate nel braccio con PM01183 (Braccio A). I campioni saranno prelevati in due cicli (nel Ciclo 1 e in un altro ciclo fra il Ciclo 2 e il Ciclo 4). La scelta del secondo ciclo in cui verranno prelevati i campioni per la misurazione di PM01183 sarà effettuata dopo che la paziente sarà stata randomizzata nel Braccio A.

E.3

Principal inclusion criteria

1) Voluntary written informed consent (IC) of the patient obtained before any study-specific procedure.
2) Age = 18 years.
3) Histologically or cytologically confirmed diagnosis of unresectable epithelial ovarian, fallopian tube or primary peritoneal cancer.
4) Platinum-resistant disease (PFI: 1-6 months after last platinumcontaining chemotherapy).
5) Radiologically measurable and/or non-measurable progressive disease according to RECIST v 1.1.
6) No more than three prior systemic chemotherapy regimens. Note: in case that a patient had started a new systemic chemotherapy without disease progression to the prior chemotherapy line (e.g., treatment discontinuations due to toxicity; neoadjuvant followed by adjuvant chemotherapy regimens), these two chemotherapy regimens will
considered as one.
7) ECOG PS = 2.
8) Adequate hematological, renal, metabolic and hepatic function:
a) Hemoglobin = 9 g/dl [patients may have received prior red blood cell (RBC) transfusion]; absolute neutrophil count (ANC) = 2.0 x 109/l, and platelet count = 100 x 109/l.
b) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3.0 x upper limit of normal (ULN).
c) Alkaline phosphatase (AP) < 5.0 x ULN.
d) Total bilirubin = ULN or direct bilirubin = ULN if total bilirubin is > ULN.
e) Albumin = 3.0 g/dl.
f) Calculated creatinine clearance (CrCL) = 30 ml/min (using Cockcroft and Gault's formula).
g) Creatine phosphokinase (CPK) = 2.5 x ULN.
9) At least three weeks since last prior therapy, and grade = 1 from any adverse event (AE) derived from previous treatment (excluding grade =
2 alopecia or peripheral neuropathy) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v. 4).
10) Women of childbearing potential must have pregnancy excluded by appropriate testing before study entry. A medically acceptable method of
contraception must be maintained throughout the treatment period and for at least six months after treatment discontinuation.

1) Consenso informato scritto (IC) volontario della paziente ottenuto prima di qualsiasi procedura specifica dello studio.
2) Età = 18 anni.
3) Diagnosi istologicamente o citologicamente confermata di carcinoma epiteliale ovarico non resecabile, cancro alle tube di Falloppio o carcinoma peritoneale primario.
4) Malattia platino-resistente (PFI: 1-6 mesi dall'ultima chemioterapia al platino).
5) Malattia progressiva radiologicamente misurabile e/o non misurabile in base a RECIST v 1.1.
6) Non più di tre regimi chemioterapici sistemici precedenti. Nota: nel caso in cui una paziente abbia iniziato una nuova chemioterapia sistemica senza progressione della malattia alla linea chemioterapica precedente (ad es. interruzione del trattamento dovuta a tossicità; regime chemioterapico neoadiuvante seguito da regime adiuvante), questi due regimi chemioterapici verranno considerati come uno solo.
7) ECOG PS = 2.
8) Funzionalità ematologica, renale, metabolica ed epatica adeguata:
a) Emoglobina = 9 g/dl [le pazienti possono aver ricevuto una precedente trasfusione di globuli rossi (RBC)]; conta assoluta dei neutrofili (ANC) = 2,0 x 109/l e conta piastrinica = 100 x 109/l.
b) Alanina aminotransferasi (ALT) e aspartato aminotransferasi (AST) = 3,0 x limite superiore della norma (ULN).
c) Fosfatasi alcalina (AP) < 5,0 x ULN.
d) Bilirubina totale = ULN o bilirubina diretta = ULN se la bilirubina totale è > ULN.
e) Albumina = 3,0 g/dl.
f) Clearance della creatina (CrCL) calcolata = 30 ml/min (utilizzando la formula di Cockcroft e Gault).
g) Fosfochinasi della creatinina (CPK) = 2,5 x ULN.
9) Almeno tre settimane dall'ultima chemioterapia precedente ed eventi avversi (AE) di grado = 1 derivanti dal trattamento precedente (esclusa alopecia o neuropatia periferica = 2) secondo i Criteri comuni di terminologia per gli eventi avversi del National Cancer Institute (NCI- CTCAE v. 4).
10) Le donne in età fertile devono presentare un test di gravidanza negativo prima dell'ingresso nello studio. È necessario impiegare un metodo contraccettivo accettabile a livello medico per tutto il periodo di trattamento e per almeno sei mesi dopo l'interruzione del trattamento.

E.4

Principal exclusion criteria

1) Concomitant diseases/conditions:
a) History of cardiac disease: myocardial infarction or
symptomatic/uncontrolled angina within the year prior to enrollment; or congestive heart failure defined as abnormal left ventricular ejection fraction (LVEF) < 50% assessed by multiple-gated acquisition scan (MUGA) or equivalent by ultrasound (US); or symptomatic arrhythmia.
b) Patients with any immunodeficiency, including those known to be infected by human immunodeficiency virus (HIV).
c) Chronic active hepatitis or cirrhosis. For Hepatitis B, this includes positive tests for both Hepatitis B surface antigen and quantitative Hepatitis B polymerase chain reaction (PCR). For Hepatitis C, this includes positive tests for both Hepatitis C antibody and quantitative Hepatitis C PCR.
d) Active uncontrolled infection.
e) Bowel obstruction.
f) Requirement of permanent or frequent (i.e., once per week) external
drainages within two weeks prior to randomization.
g) Limitation of the patient's ability to comply with the treatment or to follow-up the protocol.
h) Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study.
2) Platinum-refractory or platinum-sensitive disease (PFI <1 or > 6 months).
3) Prior treatment with PM01183, trabectedin, or with both PLD and topotecan.
Note: if 60% of recruitment is reached in one of the control treatment options (i.e., PLD or topotecan), patients could only be eligible if they did
not previously receive the other control treatment option available (the Sponsor will inform the sites, if this occurs).
4) Known brain metastases or leptomeningeal disease involvement.
5) History of another neoplastic disease (except for curatively treated basal cell carcinoma, squamous cell carcinoma of the skin, or properly treated carcinoma in situ of the uterine cervix or breast) within three years prior to randomization.
6) Pregnant or breast feeding women.

1) Patologie/condizioni concomitanti:
a) Anamnesi di cardiopatologie: infarto al miocardio o angina sintomatica/non controllata entro un anno prima dell'arruolamento; insufficienza cardiaca congestizia definita come frazione di eiezione ventricolare sinistra anomala (LVEF) < 50% valutata da scansione con acquisizione a gate multipli (MUGA) o ecografia equivalente (US); aritmia sintomatica.
b) Pazienti affette da qualsiasi immunodeficienza, compresa un'infezione nota da virus dell’immunodeficienza umana (HIV).
c) Epatite o cirrosi cronica attiva. Per l'epatite B sono inclusi i test positivi all'antigene di superficie dell'epatite B e una reazione a catena della polimerasi (PCR) quantitativa. Per l'epatite C sono inclusi i test positivi agli anticorpi dell'epatite C e una PCR quantitativa dell'epatite C.
d) Infezione attiva non controllata.
e) Ostruzione intestinale.
f) Requisito di drenaggi esterni permanenti o frequenti (ovvero una volta alla settimana) entro due settimane prima della randomizzazione.
g) Limitazione della capacità della paziente di rispettare il trattamento o di attenersi al protocollo.
h) Altre patologie importanti che, secondo il parere dello sperimentatore, aumentano sostanzialmente il rischio associato alla partecipazione della paziente a questo studio.
2) Patologia platino-refrattaria o platino-sensibile (PFI < 1 o > 6 mesi).
3) Trattamento precedente con PM01183, trabectedina o con PLD e topotecan associati.
Nota: se viene raggiunto il 60% dell'arruolamento in una delle opzioni di trattamento di controllo (ovvero PLD o topotecan), le pazienti possono essere idonee solo se non hanno ricevuto precedentemente l'altra opzione di trattamento di controllo disponibile (nel qual caso lo Sponsor informerà i centri).
4) Coinvolgimento noto di metastasi cerebrali o patologia leptomeningea.
5) Anamnesi di un'altra neoplasia (tranne il carcinoma basocellulare trattato con intento curativo, il carcinoma a cellule squamose della pelle o il carcinoma in situ della cervice uterina o del seno trattato adeguatamente) entro tre anni prima della randomizzazione.
6) Donne gravide o in allattamento.

E.5 End points

E.5.1

Primary end point(s)

Progression-free survival (PFS)

Sopravvivenza libera da progressione (PFS)

E.5.1.1

Timepoint(s) of evaluation of this end point

Along the study

durante lo studio

E.5.2

Secondary end point(s)

Progression-free survival (PFS)
Overall survival (OS)
Landmark analyses:
PFS at 6 and 12 months by IRC/IA
OS at 12 and 24 months
Best antitumor response by IRC/IA
Duration of response (DR) by IRC/IA
Best response according to tumor marker evaluation (CA-125)
Treatment safety profile
Patient-reported outcomes (PRO):
Plasma pharmacokinetics (PK) of PM01183
Subgroup analyses: Subgroup analyses of the PM01183 arm versus PLD
or topotecan
Pharmacogenetics
Pharmacogenomics

Sopravvivenza libera da progressione (PFS)
Sopravvivenza globale (OS).
Analisi dei landmark:
PFS a 6 e 12 mesi secondo IRC/IA.
OS a 12 e 24 mesi
Migliore risposta antitumorale secondo IRC/IA
Durata della risposta (DR) secondo IRC/IA
Migliore risposta in base alla valutazione del marcatore tumorale (CA- 125).
Profilo di sicurezza del trattamento
Risultati riportati dalla paziente (PRO)
Farmacocinetica (PK) plasmatica di PM01183
Analisi di sottogruppi: saranno svolte analisi di sottogruppi del braccio con PM01183 rispetto a PLD o topotecan
Farmacogenetica
Farmacogenomica.

E.5.2.1

Timepoint(s) of evaluation of this end point

Along the study

durante lo studio

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

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

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)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

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)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

doxorubicina liposomiale pegilata (PLD) o topotecan

pegylated liposomal doxorubicin hydrochloride (PLD) or topotecan

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

Information not present in EudraCT

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

Serbia

United States

Austria

Belgium

Bulgaria

Czechia

France

Germany

Hungary

Italy

Romania

Spain

United Kingdom

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

24 months after randomization of the last patient

24 mesi dopo la randomizzazione dell'ultimo paziente

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial 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:

294

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

126

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.4.2

For a multinational trial

F.4.2.1

In the EEA

265

F.4.2.2

In the whole clinical trial

420

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)

G. Investigator Networks to be involved in the Trial

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2015-07-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-07-08

P. End of Trial
P.	End of Trial Status	Completed

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Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
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