Clinical Trials Register

Summary
EudraCT Number:	2017-004058-40
Sponsor's Protocol Code Number:	EUDARIO
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:	2020-11-04
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

2017-004058-40

A.3

Full title of the trial

A multicentre, open-label, three-arm randomised Phase II trial assessing the safety and efficacy of the HSP90 inhibitor Ganetespib in combination with Carboplatin followed by maintenance treatment with Niraparib versus Ganetespib plus Carboplatin followed by Ganetespib and Niraparib versus Carboplatin in combination with standard chemotherapy followed by Niraparib maintenance treatment in platinum-sensitive ovarian cancer patients

Studio randomizzato a tre bracci di Fase II, multicentrico, in aperto, che valuta la sicurezza e l'efficacia dell'inibitore HSP90 Ganetespib in associazione con Carboplatino, seguiti da un trattamento di mantenimento con Niraparib, versus Ganetespib più Carboplatino, seguiti da Ganetespib e Niraparib, versus Carboplatino in combinazione con chemioterapia standard, seguiti dal trattamento di mantenimento con Niraparib, nei pazienti con carcinoma ovarico sensibile al platino.

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

EUDARIO: European Trial on enhanced DNA Repair Inhibition in Ovarian Cancer

EUDARIO: Sperimentazione Europea sull'inibizione indotta della riparazione del DNA nel tumore ovaric

A.4.1

Sponsor's protocol code number

EUDARIO

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN00000000

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT00000000

A.5.3

WHO Universal Trial Reference Number (UTRN)

U0000-0000-0000

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	UNIVERSITé CATHOLIQUE DE LOUVAIN
B.1.3.4	Country	Belgium
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	European Union FP7 programme (grant agreement n°602602)
B.4.2	Country	Belgium
B.4.1	Name of organisation providing support	TESARO
B.4.2	Country	United States
B.4.1	Name of organisation providing support	ALDEYRA THERAPEUTICS
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Joke De Roover
B.5.2	Functional name of contact point	Catholic University of Leuven, UZLe
B.5.3	Address:
B.5.3.1	Street Address	Herestraat 49
B.5.3.2	Town/ city	Leuven
B.5.3.3	Post code	3000
B.5.3.4	Country	Belgium
B.5.4	Telephone number	+3216347419
B.5.5	Fax number	+3216347687
B.5.6	E-mail	bgog@engot.eu

D. IMP Identification
D.IMP: 1
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	PACLITAXEL MYLAN GENERICS - 6 MG/ML CONCENTRATO PER SOLUZIONE PER INFUSIONE 1 FLACONCINO DI VETRO DA 5 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	MYLAN S.P.A.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	PACLITAXEL
D.3.2	Product code	[PACLITAXEL]
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	PACLITAXEL
D.3.9.1	CAS number	33069-62-4
D.3.9.2	Current sponsor code	PACLITAXEL
D.3.9.3	Other descriptive name	Paclitaxel
D.3.9.4	EV Substance Code	NA
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	6
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	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	Zejula
D.2.1.1.2	Name of the Marketing Authorisation holder	TESARO
D.2.1.2	Country which granted the Marketing Authorisation	United States
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/3/10/760
D.3 Description of the IMP
D.3.1	Product name	ZEJULA
D.3.2	Product code	[L-001946812-005R, L-001946812 and MK-4827]
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	niraparib tosylate monohydrate
D.3.9.1	CAS number	1038915-60-4
D.3.9.2	Current sponsor code	L-001946812-005R, L-001946812 and MK-4827
D.3.9.3	Other descriptive name	Niraparib
D.3.9.4	EV Substance Code	SUB177208
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	100
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.2.1.1.1	Trade name	GEMCITABINA ACCORD - 100 MG/ML CONCENTRATO PER SOLUZIONE PER INFUSIONE 1 FLACONCINO IN VETRO DA 10 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	ACCORD HEALTHCARE ITALIA S.R.L.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Gemcitabina
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	GEMCITABINA
D.3.9.1	CAS number	95058-18-4
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	Gemcitabina
D.3.9.4	EV Substance Code	NA
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	100
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: 4
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	CARBOPLATINO AHCL - 10 MG/ML CONCENTRATO PER SOLUZIONE PER INFUSIONE 1 FLACONCINO DI VETRO DA 5 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	ACCORD HEALTHCARE LIMITED
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	CARBOPLATINO
D.3.2	Product code	[Carboplatino]
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	CARBOPLATINO
D.3.9.1	CAS number	41575-94-4
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	Carboplatino
D.3.9.4	EV Substance Code	NA
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	10
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: 5
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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	GANETESPIB
D.3.2	Product code	[STA-909]
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	GANETESPIB
D.3.9.1	CAS number	888216-25-9
D.3.9.2	Current sponsor code	Ganetespib (STA-9090)
D.3.9.3	Other descriptive name	Ganetespib
D.3.9.4	EV Substance Code	SUB88334
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	25
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: 6
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	CARBOPLATINO AHCL - 10 MG/ML CONCENTRATO PER SOLUZIONE PER INFUSIONE 1 FLACONCINO DI VETRO DA 5 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	ACCORD HEALTHCARE LIMITED
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	CARBOPLATINO
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	CARBOPLATINO
D.3.9.1	CAS number	41575-94-4
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	Carboplatino
D.3.9.4	EV Substance Code	NA
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	10
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 sensitive ovarian cancer, carcinosarcoma, primary peritoneal or Falloppian tube cancer

Carcinoma epiteliale ovarico platino sensibile, carcinosarcoma, carcinoma delle tube di Falloppio o primitivo del peritoneo

E.1.1.1

Medical condition in easily understood language

ovarian cancer, carcinosarcoma, primary peritoneal or Falloppian tube cancer

carcinoma ovarico, carcinosarcoma, carcinoma delle tube di Falloppio o primitivo del peritoneo

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	10016180
E.1.2	Term	Fallopian tube 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	10006888
E.1.2	Term	Ca ovary
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	21.0
E.1.2	Level	PT
E.1.2	Classification code	10061269
E.1.2	Term	Malignant peritoneal neoplasm
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	10052204
E.1.2	Term	Ovarian carcinosarcoma
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

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To determine the progression-free survival (PFS) by RECIST 1.1

Determinare l'intervallo libero da progressione di malattia (PFS) secondo i criteri RECIST 1.1

E.2.2

Secondary objectives of the trial

- To determine the progression-free survival (PFS)
- To determine the post-progression progression-free survival (PFS2)
- To determine the time to first subsequent therapy (TFST)
- To determine the time to second subsequent therapy (TSST)
- To determine the safety of the therapy
- To determine the objective response rate (ORR)
- To determine the patient reported outcome
- To determine the overall survival (OS)

- Determinare la PFS valutata in sottogruppi predefiniti
- Determinare la PFS dopo la prima progressione (PFS2)
- Determinare il tempo che intercorre tra la fine della prima linea chemioterapica e la successiva (TFST)
- Determinare il tempo che intercorre tra la fine della prima linea di chemioterapia e la seconda linea dopo la successiva (TSST)
- Determinare la sicurezza del trattamento sperimentale: eventi avversi (AE), secondo NCI CTCAE, versione 4.03
- Determinare il tasso di risposta obiettiva (ORR)
- Valutare la qualità di vita delle pazienti
- Determinare la sopravvivenza globale (OS)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Ability to understand and willingness to sign and date a written informed consent document
• Female patients = 18 year of age
• High-grade serous, high grade endometrioid, undifferentiated epithelial ovarian, or carcinosarcoma, fallopian tube or primary peritoneal cancer
• Platinum-sensitive relapse > 6 months after previous platinum-based treatment (calculated from the first day of the last cycle of the last platinum based chemotherapy until the date of progression confirmed according to RECIST 1.1 on imaging)
• No limits in number of prior treatment lines
• Measurable or evaluable disease according to RECIST 1.1
• ECOG performance status 0-1
• Adequate functions of the bone marrow: o Platelets = 100 x 109/L o Absolute neutrophil count (ANC) = 1.5 x 109/L
• Adequate function of the organs: o Creatinine < 2 mg/dl (<177 µmol/L) o Total bilirubin = 1.5 x upper limit of normal (= 2.0 in patients with known Gilberts syndrome) OR direct bilirubin = 1 x ULN o SGOT/SGPT (AST/ALT) = 2.5 x upper limit of normal unless liver metastases are present, in which case they must be = 5 x ULN o Urinanalysis or urine dipstick for proteinuria less than 2+. Patients with = 2+ on dipstick should undergo 24-hour urine collection and must demonstrate < 1 g of protein/24 hours; except the proteinuria is clearly related to a catheter in the urinary system.
• Adequate coagulation parameter: aPTT = 1.5 x ULN (patients on heparin treatment must have an aPTT between 1.5-2.5 x ULN), or INR = 1.5. (In patients receiving anticoagulants (such as warfarin) INR must be between 2.0 and 3.0 in two consecutive measurements 1-4 days apart).
• Participant receiving corticosteroids (dose < 10 mg/day methylprednisolone equivalent), including inhaled steroids, may continue as long as their dose is stable for at least 4 weeks prior to initiating protocol therapy.
• Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment.
• Female participant has a negative serum pregnancy test within 7 days prior to taking study treatment if of childbearing potential and agrees to abstain from activities that could result in pregnancy from screening through 180 days after the last dose of study treatment, or is of nonchildbearing potential.
• Participant must agree to not breastfeed (or store breast milk for use) during the study or for 180 days afer the last dose of study treatment.
• Haemoglobin =8.5 g/dl (patients may not receive a transfusion within 4 weeks prior to initiating study treatment)
• Able to take oral medications
• Availability of archival ovarian cancer tissue from primary diagnosis (delivery of FFPE block or slides is prerequisite for randomisation)

• Capacità di comprendere e volontà di firmare il modulo di consenso informato
• Donne di età =18 anni
• Tumore ovarico epiteliale indifferenziato, sieroso di alto grado, endometrioide di alto grado, carcinosarcoma, tumore primitivo del peritoneo o della tuba di Falloppio.
• Recidiva sensibile al platino > 6 mesi dopo un precedente trattamento a base di platino (calcolato dal primo giorno dell'ultimo ciclo dell'ultima chemioterapia a base di platino fino alla data della progressione confermata in base ai criteri RECIST 1.1)
• Nessun limite nel numero di precedenti linee di terapia
• Malattia misurabile o valutabile secondo criteri RECIST 1.1
• ECOG Performance Status 0-1
• Adeguata funzionalità emopoietica, definita come:
o Conta piastrinica = 100 x 109/L
o ANC = 1,5 x 109 / L
• Adeguata funzionalità d’organi, definita come di seguito:
o Creatinina < 2 mg/dl (<177 µmol/L)
o Bilirubina totale sierica = 1.5 ULN istituzionale ad eccezione di presenza della sindrome di Gilbert. In tal caso il valore di bilirubina totale sierica deve essere = 2 x ULN istituzionale
o SGOT/SGPT (AST / ALT) = 2.5 x ULN istituzionale (o = 5 x ULN se sono presenti metastasi epatiche)
o Urinanalisi o dipstick test per proteinuria inferiore a 2+.
Le pazienti con valore = 2+ devono essere sottoposte a raccolta delle urine delle 24 ore e devono mostrare un valore <1 g di proteine/24 ore; a meno che la proteinuria sia chiaramente correlata ad un catetere nel sistema urinario.
• aPTT = 1,5 x ULN (i pazienti in trattamento con eparina devono avere un aPTT compreso tra 1,5-2,5 x ULN) o INR = 1,5. (Nei pazienti che ricevono anticoagulanti (come il warfarin) deve essere compreso tra 2,0 e 3,0 in due misurazioni consecutive da 1 a 4 giorni di distanza).
• Le pazienti che ricevono corticosteroidi (dose <10 mg/die di metilprednisolone), compresi gli steroidi per via inalatoria, possono continuare fino a quando la loro dose è stabile per almeno 4 settimane prima di iniziare la terapia prevista dallo studio.
• Le pazienti devono accettare di non donare sangue durante lo studio e per 90 giorni dopo l'ultima dose di trattamento in studio
• Le donne in età fertile devono risultare negative al test di gravidanza nei 7 giorni precedenti l’arruolamento nello studio e accettare di astenersi da attività che potrebbero causare una gravidanza, dallo screening fino a 180 giorni dopo l'ultima dose del trattamento di studio.
• La partecipante deve accettare di non allattare (o conservare il latte materno per l'uso) durante lo studio o per 180 giorni dopo l'ultima dose del trattamento di studio.
• Emoglobina =8,5 g / dl (le pazienti non possono ricevere una trasfusione entro 4 settimane prima di iniziare il trattamento in studio)
• Le pazienti devono essere in grado di assumere farmaci orali
• Disponibilità di tessuto tumorale archiviato dalla diagnosi primaria (la consegna del blocco o vetrino FFPE è un prerequisito per la randomizzazione)
• Prima dell'inizio della terapia di mantenimento, le pazienti devono mostrare i seguenti valori degli esami di laboratorio:
o Conteggio assoluto dei neutrofili = 1.500 / µL
o Piastrine = 100.000 / µl
o Emoglobina = 9 g / dL
o Creatinina sierica = 1,5 x limite superiore del normale (ULN) o clearance della creatinina calcolata = 30 ml / min utilizzando l'equazione di Cockcroft-Gault
o Bilirubina totale = 1,5 x ULN (= 2,0 nei pazienti con sindrome di Gilberts nota) o bilirubina diretta = 1 x ULN
o Aspartato aminotransferasi e alanina aminotransferasi = 2,5 x ULN (o = 5 x ULN se sono presenti metastasi epatiche)

E.4

Principal exclusion criteria

• Ovarian tumours with low malignant potential (i.e. borderline tumours)
• Any prior radiotherapy to the pelvis or abdomen, or any radiotherapy encompassing > 20 % of the bone marrow within 2 weeks, or any radiotherapy within 1 week prior to Day 1 of protocol therapy.
• Surgery (including open biopsy and traumatic injury) within 4 weeks prior to first dose of Ganetespib, or anticipation of the need for major surgery during study treatment • Minor surgical procedures, within 24 hours prior to the first study treatment
• Known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
• Any serious, uncontrolled medical disorder, non-malignant systemic disease, or active, uncontrolled infection.
• Current or recent (within 10 days prior to the first study drug dose) chronic daily treatment with aspirin (> 325 mg/day).
• Patients with a history of diagnosis, detection or treatment of any prior malignancies = 2 years prior to initiating protocol therapy, except: basal or squamous cell carcinoma of the skin and cervical cancer that has been definitively treated.
• Clinically significant gastro-intestinal (GI) tract abnormalities that may increase the risk for GI bleeding and / or perforation
• Non-healing wound or non-healing bone fracture
• Patients with symptomatic brain or leptomeningeal metastases (patients who are asyptomatic since treatment of brain or leptomeningeal metastases, eg after irradiation, are eligible)
• Left ventricular ejection fraction (LVEF) defined by ECHO below the institutional lower limit of normal
• Cerebrovascular accident (CVA)/ stroke or transient ischemic attack (TIA) or sub-arachnoid haemorrhage within = 6 months prior to first study treatment.
• Significant cardiac disease: New Yourk Heart Assiciation (NYHA) Class 3 or 4; myocardial infarction within the past 6 months; unstable angina; coronary angioplasty or coronary atrial or ventricular cardiac arrhythmias
• History of prolonged QT syndrome, or family member with prolonged QT syndrome
• QTc interval > 470 msec when 3 consecutive ECG values are averaged
• Ventricular tachycardia or a supraventricular tachycardia that requires treatment with a Class Ia antiarrhythmic drug (e.g. sotalol, amiodarone, dofetilide). Use of other antiarrhythmic drugs is permitted • Second- or third-degree atrioventricular (AV) block, except: treated with a permanent pacemaker
• Complete left bundle branch block (LBBB) • History of evidence of haemorrhagic disorders, patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorders, coagulopathy or tumour involving major vessels.
• Participation in another clinical study with experimental therapy within 28 days before start of treatment.
• Participant must not be simultaneously enrolled in any interventional clinical trial.
• Women who are pregnant or are lactating • Patients unable to be regularly followed for any reason (geographic, familiar, social, psychologic, housed in an institution eg. prison because of a court agreement or administrative order)
• Subjects that are dependent on the sponsor/CRO or investigational site as well as on the investigator.
• History of known hypersensibility against any medication used in the study
• Intolerance / Hypersensitivity reactions to components and exipients of study drugs
• Peripheral neuropathy of grade >2 per NCI CTCAE, version 4.03, within 4 weeks prior to randomisation
• Any other condition that, in the opinion of the investigator, may compromise the safety, compliance of the patient, or would preclude the patient from successful completion of the study

• Tumori ovarici con basso potenziale maligno (tumori borderline)
• Qualsiasi precedente radioterapia alla pelvi o all'addome, o qualsiasi radioterapia che interessi > 20% del midollo osseo entro 2 settimane, o qualsiasi radioterapia entro 1 settimana prima del primo giorno della terapia prevista dal protocollo
• Chirurgia (inclusa biopsia aperta e lesione traumatica) nelle 4 settimane precedenti la prima dose di Ganetespib o interventi chirurgici di maggiore entità anticipati durante il trattamento di studio
• Procedure chirurgiche minori, entro 24 ore prima del primo trattamento previsto dallo studio
• Storia nota di sindrome mielodisplastica (MDS) o di leucemia mieloide acuta (LMA)
• Qualsiasi malattia grave, incontrollata, malattia sistemica non maligna o infezione attiva e incontrollata.
• Trattamento cronico giornaliero con aspirina (>325mg/die), in corso o recente (nei 10 giorni precedenti la prima dose del farmaco in studio)
• Pazienti con una storia di diagnosi, accertamento o trattamento di neoplasie pregresse = 2 anni prima di iniziare la terapia prevista dallo studio, eccetto: carcinoma basocellulare o squamoso della pelle e carcinoma della cervice che è stato definitivamente trattato
• Anomalie gastro-intestinali clinicamente significative che possano aumentare il rischio di sanguinamento e/o perforazione gastrointestinale
• Ferite o fratture ossee non cicatrizzate
• Pazienti con metastasi sintomatiche cerebrali o leptomeningee (pazienti asintomatiche dal momento del trattamento di metastasi cerebrali o leptomeningee, ad esempio dopo l'irradiazione, sono ammissibili)
• Frazione di eiezione ventricolare sinistra (LVEF) al di sotto del limite inferiore normale standard (definita come da ECHO)
• CVA/ictus, attacco ischemico transitorio (TIA) o emorragia subaracnoidea entro = 6 mesi prima dell’inizio del trattamento previsto dallo studio
• Patologia cardiaca significativa: New Yourk Heart Association (NYHA) di grado 3 o 4; infarto miocardico negli ultimi 6 mesi; angina instabile; angioplastica coronarica o aritmia cardiaca atriale o ventricolare
• Anamnesi di sindrome del QT lungo o membro della famiglia affetto da sindrome del QT lungo
• Intervallo QTc> 470 msec come media di 3 consecutive misurazioni
• Tachicardia ventricolare o tachicardia sopraventricolare che richiede il trattamento con un farmaco antiaritmico di classe Ia (ad esempio sotalolo, amiodarone, dofetilide). È consentito l'uso di altri farmaci antiaritmici
• Blocco atrioventricolare (AV) di secondo o terzo grado, a meno che trattato con un pacemaker permanente
• Blocco di branca sinistro completo (LBBB)
• Anamnesi di disturbi emorragici, pazienti con sanguinamento attivo o condizioni patologiche ad alto rischio di sanguinamento, quali disturbi emorragici noti, coagulopatia o tumore che coinvolge i vasi maggiori
• Partecipazione ad un altro studio clinico con terapia sperimentale entro 28 giorni prima dell'inizio del trattamento
• Le pazienti non devono partecipare contemporaneamente ad altre sperimentazioni cliniche interventistiche
• Donne in stato di gravidanza o allattamento
• Pazienti incapaci di essere seguite regolarmente per qualsiasi motivo (geografico, familiare, sociale, psicologico, ristretti presso un istituto, ad esempio un istituto penitenziario a seguito di decisione giudiziaria o di un ordine amministrativo)
• Pazienti che dipendono dallo sponsor/CRO o dal centro clinico e dallo sperimentatore
• Anamnesi di ipersensibilità nota rispetto a qualsiasi farmaco utilizzato nello studio
• Reazioni di intolleranza/ipersensibilità a componenti ed eccipienti di farmaci in studio
• Neuropatia periferica di grado> 2 secondo NCI CTCAE, versione 4.03, entro 4 settimane prima della randomizzazione
• Qualsiasi altra condizione che, secondo il parere dello sperimentatore, possa compromettere la sicurezza e la compliance del paziente o che impedirebbe la conclusione dello studio da parte delle pazienti

E.5 End points

E.5.1

Primary end point(s)

Progression-free survival (PFS) by RECIST 1.1

Intervallo libero da progressione di malattia (PFS) valutato secondo criteri RECIST 1.1

E.5.1.1

Timepoint(s) of evaluation of this end point

Evaluation will be done 6 months after LPI, this is expected in Q1 2020

La valutazione verrà effettuata 6 mesi dopo l'inclusione dell'ultimo paziente, prevista per il primo quadrimestre del 2020

E.5.2

Secondary end point(s)

- PFS according to pre-defined subgroups
- Post-progression PFS (PFS2)
- Time to First Subsequent Therapy (TFST)
- Time to Second Subsequent Therapy (TSST)
- Safety: Adverse events (AEs), measure according to NCI CTCAE, version 4.03
- Objective response rate (ORR)
- Patient-reported outcome (PRO)
- Overall survival (OS)

- PFS valutata in sottogruppi predefiniti
- PFS dopo la prima progressione (PFS2)
- Tempo che intercorre tra la fine della prima linea chemioterapica e la successiva (TFST)
- Tempo che intercorre tra la fine della prima linea di chemioterapia e la seconda linea dopo la successiva (TSST)
- Sicurezza del trattamento sperimentale: eventi avversi (AE), secondo NCI CTCAE, versione 4.03
- Tasso di risposta obiettiva (ORR)
- Patient-reported outcome (PRO)
- Sopravvivenza globale (OS)

E.5.2.1

Timepoint(s) of evaluation of this end point

Evaluation will be done 1 to 1.5 years after the evaluation of the primary end point, this is therefore expected in Q1 - Q3 2021

La valutazione verrà eseguita da 1 a 1,5 anni dopo la valutazione dell'endpoint primario, pertanto è prevista tra il primo ed il terzo trimestre del 2021

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

E.6.7

Pharmacodynamic

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

Yes

E.6.13.1

Other scope of the trial description

Biomarker analysis on DNA, RNA and protein level

Analisi di marcatori biochimici e biomolecolari

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

Yes

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

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

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

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

LVLS

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

120

F.4.2.2

In the whole clinical trial

120

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)

Patients who discontinue study treatment without having developed progressive disease will first continue to be followed monthly until progression and will then continue with long-term follow-up after progression
In all patient a long-term follow-up period will be performed after the safety follow-up visits.
In patients who had end of treatment due to progression of disease, information about patient's health shoulb be recorded in three-monthly intervals until death of the patients.

I pazienti che interrompono il trattamento senza aver sviluppato una progressione della malattia continueranno ad essere seguiti ogni mese fino alla progressione e continueranno con il follow-up a lungo termine dopo la progressione
I pazienti che hanno interrotto il trattamento per progressione di malattia, verranno contattati ogni tre mesi per raccogliere informazioni sul loro stato di salute, fino alla loro morte.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	NOGGO
G.4.3.4	Network Country	Germany
G.4 Investigator Network to be involved in the Trial: 2
G.4.1	Name of Organisation	AGO Austria
G.4.3.4	Network Country	Austria
G.4 Investigator Network to be involved in the Trial: 3
G.4.1	Name of Organisation	GINECO
G.4.3.4	Network Country	France
G.4 Investigator Network to be involved in the Trial: 4
G.4.1	Name of Organisation	BGOG
G.4.3.4	Network Country	Belgium
G.4 Investigator Network to be involved in the Trial: 5
G.4.1	Name of Organisation	MITO
G.4.3.4	Network Country	Italy

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-03-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-10-26

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

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Orphan Designation Number:
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