Clinical Trials Register

Summary
EudraCT Number:	2012-004362-17
Sponsor's Protocol Code Number:	MITO-16b/MANGO-OV2b/ENGOT-OV17
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2015-06-17
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

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A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2012-004362-17

A.3

Full title of the trial

A multicenter phase III randomized study with second line chemotherapy plus or minus bevacizumab in patients with platinum sensitive epithelial ovarian cancer recurrence after a bevacizumab/chemotherapy first line

Essai randomisé, multicentrique de phase III, comparant une deuxième ligne de chimiothérapie avec ou sans bevacizumab chez des patientes atteintes d’un adénocarcinome de l’ovaire en rechute sensible au platine, ayant reçu du bevacizumab en 1ère ligne.

A.3.1

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

Essai comparant une deuxième ligne de chimiothérapie avec ou sans bevacizumab chez des patientes atteintes d’un adénocarcinome de l’ovaire en rechute sensible au platine, ayant reçu du bevacizumab en 1ère ligne.

A.4.1

Sponsor's protocol code number

MITO-16b/MANGO-OV2b/ENGOT-OV17

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	ISTITUTO NAZIONALE PER LO STUDIO E LA CURA DEI TUMORI - FONDAZIONE 'G. PASCALE'
B.1.3.4	Country	Italy
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	Roche
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Arcagy-Gineco
B.5.2	Functional name of contact point	Project leader
B.5.3	Address:
B.5.3.1	Street Address	Hopital Hotel Dieu , 1 place du parvis de notre dame
B.5.3.2	Town/ city	Paris
B.5.3.3	Post code	75004
B.5.3.4	Country	France
B.5.4	Telephone number	33142348323
B.5.5	Fax number	33143262673
B.5.6	E-mail	fmarmion@arcagy.org

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	AVASTIN*INF 400MG 16ML 25MG/ML
D.2.1.1.2	Name of the Marketing Authorisation holder	ROCHE SpA
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.3.4	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	BEVACIZUMAB
D.3.9.1	CAS number	216974-75-3
D.3.9.4	EV Substance Code	SUB16402MIG
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	400
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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 patients progressing or recurring after a first-line treatment including bevacizumab.

patientes atteinte d'un cancer de l'ovaire sensible au platine et progressant après une 1ere ligne de chimiothérapie incluant du bevacizumab

E.1.1.1

Medical condition in easily understood language

platinum sensitive ovarian cancer patients progressing or recurring after a first-line treatment including bevacizumab.

patiente en 2eme ligne de traitement d'un cancer de l'ovaire

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	18.0
E.1.2	Level	PT
E.1.2	Classification code	10066697
E.1.2	Term	Ovarian cancer recurrent
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

The primary objective of this trial is to test whether the addition of bevacizumab to second-line chemotherapy can prolong progression-free survival (PFS) of platinum sensitive ovarian cancer patients progressing or recurring after a first-line treatment including bevacizumab.

Tester si l’addition de bevacizumab à une chimiothérapie de deuxième ligne augmente la survie sans progression (PFS) chez des patientes atteintes d’un adénocarcinome de l’ovaire sensible au platine, ayant déjà reçu du bevacizumab en première ligne.

E.2.2

Secondary objectives of the trial

Overall Survival (OS), response rate (RR), safety, as secondary end-points, will be also assessed.
Exploratory objectives for this study are to assess the correlation of baseline plasma biomarker expression with clinical outcome, as measured by PFS and OS and to evaluate the association of other potential biomarkers, including, but not limited to, the single-nucleotide polymorphisms (SNPs), other potential plasma biomarkers, and tumor-specific markers as well as clinical factors with clinical outcome. Describing the prevalence of use of oral antidiabetic as well as antithrombotic drugs will also be considered as a secondary objective.

- Survie globale (OS),
- Taux de réponse (RR),
- Tolérance.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Female patients 18 years of age.
• Patients with histologically confirmed EOC, fallopian tube carcinoma or PC, including mixed Mullerian Tumours
• Recurrence or progression at least 6 months after the last chemotherapy cycle of a first line carboplatin + paclitaxel chemotherapy including bevacizumab (recurrence or progression might occur either during or after bevacizumab as maintenance)
• Patients can be included if they have a RECIST progression, with either measurable or non-measurable disease
• ECOG Performance Status of 0–2.
• Life expectancy of 12 weeks.
• Signed informed consent obtained prior to initiation of any study-specific procedures and treatment as confirmation of the patient’s awareness and willingness to comply with the study requirements including blood samples for molecular analyses.
• Availability of tumour samples for molecular analyses from primary surgery (mandatory) and secondary surgery (when available)

1. Age ≥ 18 ans.
2. Preuve histologique d’un cancer épithélial de l’ovaire, d’un carcinome des trompes de Fallope, y compris des tumeurs mixtes müllériennes.
3. Rechute ou progression au moins 6 mois après le dernier cycle de chimiothérapie de 1ère ligne (carboplatine + paclitaxel + bevacizumab). La rechute ou progression peut avoir lieu pendant le traitement d’entretien au bevacizumab.
4. Etat de performance ECOG 0 ou 1.
5. Espérance de vie d’au moins 12 semaines.
6. Consentement éclairé signé avant toute procédure spécifique de l’étude.
7. Accessibilité aux échantillons de tumeurs pour analyse moléculaire durant la première chirurgie (obligatoire) et la seconde chirurgie (si disponible).

E.4

Principal exclusion criteria

• Ovarian tumours with low malignant potential (i.e. borderline tumours)
• History or evidence of synchronous primary endometrial carcinoma, unless all of the following criteria related to the endometrial carcinoma are met:
o stage ≤Ia
o no more than superficial myometrial invasion
o no lymphovascular invasion
o not poorly differentiated (grade 3 or papillary serous or clear cell carcinoma).
• Other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer.

1. Tumeur de l’ovaire à faible potentiel de malignité (tumeurs « borderline »).
2. Présence concomitante ou antécédent de carcinome endométrial primaire, sauf si tous les critères suivants sont présents :
- Stade ≤ Ia,
- invasion limitée au myomètre,
- Absence d’invasion lymphovasculaire,
- Absence de tumeur peu différenciée (grade 3, séreux papillaire ou carcinome à cellules claires).
3. Antécédent de tumeur maligne dans les 5 dernières années à l’exception d’un carcinome in situ du col utérin, d’un carcinome squameux de la peau correctement traité ou d’un cancer baso-cellulaire traité et contrôlé.
4. Patiente ayant reçu plus d’une ligne de chimiothérapie.
5. Antécédent de traitement avec un anti-angiogénique autre que le bevacizumab.
6. Antécédent de radiothérapie abdomino-pelvienne.

E.5 End points

E.5.1

Primary end point(s)

PFS will be the primary end-point.

PFS

E.5.1.1

Timepoint(s) of evaluation of this end point

PFS will be measured from the date of randomization to the date of progression (defined by the investigator) or the date of death, whichever comes first.

PFS mesurée de la date de randomisation à la date de progression ou la date du décès si celui ci intervient avant

E.5.2

Secondary end point(s)

• OS will be measured from the date of randomization to the date of death
• PFS defined by central independent review
• ORR will be assessed according to RECIST version 1.1
• Identification of prognostic and predictive molecular factors

- Taux de non progression à 1 an selon les critères RECIST 1.1,
- Toxicités dose-limitantes, selon les critères CTCAE v.4.03,
- Qualité de vie : échelle visuelle analogique.

E.5.2.1

Timepoint(s) of evaluation of this end point

OS will be measured as the time between the randomisation and death for any cause of the patient.
PFS as assessed by the central independent review, will be measured as the time between the randomisation and the progression (assessed by central independent review) or the death of the patient whichever occurs first

La survie globale sera mesurée au moment de la randomisation et le décès.

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

Yes

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)

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

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

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

Number of subjects for this age range:

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:

300

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

100

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

400

F.4.2.2

In the whole clinical trial

400

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 will end the study after progression of their disease. At that point they will be evaluated under normal practice circumstances for the prosecution of the care.

Le pazienti usciranno dallo studio alla progressione di malattia. A quel punto saranno valuate per la prosecuzione delle cure nell'ambito delle narmali attività di assistenza dei centri presso cui sono in cura.

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	MANGO
G.4 Investigator Network to be involved in the Trial: 2
G.4.1	Name of Organisation	MITO

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2013-12-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-11-09

P. End of Trial
P.	End of Trial Status	Ongoing

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