Clinical Trials Register

Summary
EudraCT Number:	2015-004762-28
Sponsor's Protocol Code Number:	OsteoREC2015
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2020-11-04
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2015-004762-28

A.3

Full title of the trial

Multicentric prospective, randomized, clinical trial for the treatment of patient with relapsed Osteosarcoma (OS)

Studio clinico multicentrico, prospettico, randomizzato per il trattamento dei pazienti con osteosarcoma (OS) in recidiva, 2015

A.3.1

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

Clinical trial for the relapsed Osteosarcoma treatment

Studio per il trattamento dell'osteosarcoma in recidiva

A.3.2

Name or abbreviated title of the trial where available

OsteoREC2015

A.4.1

Sponsor's protocol code number

OsteoREC2015

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	ITALIAN SARCOMA GROUP
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	Fondi Italian Sarcoma Group
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Italian Sarcoma Group
B.5.2	Functional name of contact point	Clinical Trial Unit
B.5.3	Address:
B.5.3.1	Street Address	Via Pupilli 1
B.5.3.2	Town/ city	Bologna
B.5.3.3	Post code	40136
B.5.3.4	Country	Italy
B.5.4	Telephone number	0516366668
B.5.5	Fax number	0516366400
B.5.6	E-mail	emanuela.marchesi@ior.it

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	GEMCITABINA ACCORD - 100 MG/ML CONCENTRATO PER SOLUZIONE PER INFUSIONE 1 FLACONCINO IN VETRO DA 2 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	Gemcitabina
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	95058-81-4
D.3.9.2	Current sponsor code	Gemcitabina
D.3.10	Strength
D.3.10.1	Concentration unit	mg/m2 milligram(s)/square meter
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	900
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	DOCETAXEL HAMELN RDS - 20 MG/0.5 ML CONCENTRATO E SOLVENTE PER SOLUZIONE PER INFUSIONE 1 FLACONCINO IN VETRO CONCENTRATO 20 MG/0.5 ML+1 FLACONCINO IN VETRO SOLVENTE 1.5 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	HAMELN RDS GMBH
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	Docetaxel
D.3.2	Product code	Docetaxel
D.3.4	Pharmaceutical form	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	DOCETAXEL
D.3.9.1	CAS number	114977-28-5
D.3.9.2	Current sponsor code	DOCETAXEL
D.3.9.3	Other descriptive name	DOCETAXEL
D.3.10	Strength
D.3.10.1	Concentration unit	mg/m2 milligram(s)/square meter
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	75
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	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	HOLOXAN - 1 G POLVERE PER SOLUZIONE INIETTABILE 1 FLACONCINO
D.2.1.1.2	Name of the Marketing Authorisation holder	BAXTER 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	ifosfamide
D.3.4	Pharmaceutical form	Powder 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	IFOSFAMIDE
D.3.9.1	CAS number	3778-73-2
D.3.9.2	Current sponsor code	IFOSFAMIDE
D.3.9.3	Other descriptive name	IFOSFAMIDE
D.3.10	Strength
D.3.10.1	Concentration unit	gm/m2 gram(s)/square meter
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	14
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

high grade relapsed osteosarcoma

recidiva di osteosarcoma (OS) ad alto grado di malignit¿

E.1.1.1

Medical condition in easily understood language

relapsed osteosarcoma

osteosarcoma ricaduto

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	10031291
E.1.2	Term	Osteosarcoma
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

Efficacy, safety and clinical benefit in patients with relapsed osteosarcoma (OS) treated with High dose ifosfamide or with Gemcitabine+docetaxel

Confrontare efficacia, tossicit¿ e beneficio clinico osservati nei pazienti con diagnosi di Osteosarcoma in recidiva trattati con Ifosfamide ad alte dosi (HD-IFO) in infusione continua di 14 giorni o con Gemcitabina-Docetaxel (Gem-Dox).

E.2.2

Secondary objectives of the trial

none

nessuno

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1)High grade relapsed OS
2)Relapsed disease within 24months form the inital diagnosis
3) Plural-lung relapse with more than 2 nodules
4) First releapsed disease (regardless the site) not amenable for surgery
5) Second relapse regardless the site and resecability
6) Age = 4 yrs
7)Lansky score o Karnofsky Performance status >60%
8) Notrmal for age kidney and liver functionality
9) LVEF > 50%.
10) WBC 3 x 109/L, plateelets >100 x 109/l.
11) Negative pregnancy test for female and effective contraception method for potentially feritile females
For fertile female patients is required a contraception methods needs to be taken for all the treatment period. Contraception method for male patients need to taken up to 6 month to the end of treatment

12) Provvision of written Informed Consent

1. Diagnosi di recidiva di osteosarcoma ad alto grado di malignità.
2. Pazienti con prima recidiva di malattia resecabile o non resecabile insorta entro 24 mesi dalla diagnosi iniziale di osteosarcoma ad alto grado di malignità.
3. Pazienti con recidiva pleuro-polmonare che si presentano con più di 2 noduli e oltre i 24 mesi dalla diagnosi iniziale.
4.Pazienti in prima recidiva in qualunque sede, non resecabile, insorta oltre i 24 mesi dalla diagnosi iniziale.
5.Pazienti con seconda o ulteriore recidiva di osteosarcoma ad alto grado di malignità,in qualunque sede, resecabile o non resecabile.
6. Età alla diagnosi = 4anni.
7.Lansky score o Karnofsky Performance status >60%
8. Funzionalità renale ed epatica nei limiti di normalità per l’età.
9. Frazione di eiezione ventricolare > 50%.
10. Globuli bianchi >3 x 109/le piastrine >100 x 109/l.
11. I soggetti di sesso femminile che abbiano già avuto menarca, devono presentare un test di gravidanza negativo prima dell’inizio dello studio. Per i pazienti in età fertile l'utilizzo di metodi contraccettivi deve essere esteso a tutta la durate dell'esposizione sistemica rilevante. Per quanto riguarda gli uomini, l'utilizzo di queste misure di riduzione del rischio deve protrarsi anche fino a 6 mesi dopo la fine del trattamento
12. Sottoscrizione del modulo di consenso alla partecipazione allo studio da parte del soggetto interessato o di chi ne esercita la patria potestà.

E.4

Principal exclusion criteria

1) Clincal controindications to the use of IMPs.
2) Social, psycological and geographical condition that could comprimise/jeopadize the study.
3) Active HIV, HBV e HCV infection
4) Pregnancy or breast feeding
5) Previous treatment with Gem-Dox and/or HD-IFO).

1. Controindicazioni mediche all'uso dei farmaci previsti dal protocollo.
2. Condizioni mentali,sociali e geografiche che non garantiscano un’adeguata adesione al Protocollo, una corretta gestione domiciliare della tossicità o un’adeguata comprensione dello studio.
3. Infezione da HIV, HBV e HCV in fase attiva.
4. Stato di gravidanza o allattamento
5. Precedente trattamento con Gem-Dox e/o HD-IFO.

E.5 End points

E.5.1

Primary end point(s)

6 months Progression Free Survival (PFS)

Progression Free Survival (PFS) a 6 mesi.

E.5.1.1

Timepoint(s) of evaluation of this end point

6 months

6 mesi

E.5.2

Secondary end point(s)

Overall Survival (OS); Toxicity ; Quality of Life; Hospitalization time ; Rate of post-chemotheray surgical interventions; Overall Response Rate (ORR) Overall

Overall Survival (OS) ; Tossicit¿; Qualit¿ della vita; Tempo di ospedalizzazione ; Tasso di operabilit¿ post chemioterapia; Overall Response Rate (ORR)

E.5.2.1

Timepoint(s) of evaluation of this end point

At time of death; After each cycle; At the end of Chemotheerap; fter each cycle; After 6 cycles; After 6 cycles

Al tempo del decess; Dopo ogni ciclo ; A fine trattamento; Ad ogni ciclo per Tempo di ; Dopo 6 cicli; After 6 cycles

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

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

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

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

Yes

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

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

Yes

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

100

F.4.2

For a multinational trial

F.4.2.1

In the EEA

100

F.4.2.2

In the whole clinical trial

100

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)

pts will be treated according the OS guidelines

i pz verranno trattati secondo le linee guida dell'osteosarcoma

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

2016-01-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-02-25

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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