Clinical Trials Register

Summary
EudraCT Number:	2012-004058-27
Sponsor's Protocol Code Number:	IOV-CAR-CRC-1-2012
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:	2013-01-11
Trial results

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

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2012-004058-27

A.3

Full title of the trial

Cytoreductive surgery associated with Hyperthermic Intraperitoneal Chemotherapy versus standard Chemotherapy in the treatment of resectable colorectal carcinomatosis. A multicentric open randomized clinical trial.

Chirurgia Citoriduttiva associata a Chemioterapia Ipertermica Intraperitoneale Versus Chemioterapia sistemica nel trattamento della carcinosi colorettale resecabile. Studio clinico randomizzato multicentrico in aperto.

A.3.1

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

Randomized study comparing surgery and local chemotherapy versus standard chemotherapy in the treatment of colorectal carcinomatosis.

Studio randomizzato di confronto tra chirurgia e chemioterapia locale rispetto a chemioterapia sistemica nel trattamento della carcinosi peritoneale da tumore del colon retto.

A.4.1

Sponsor's protocol code number

IOV-CAR-CRC-1-2012

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 ONCOLOGICO VENETO
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	Istituto Oncologico Veneto - IRCCS
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	Istituto Oncologico Veneto - IRCCS
B.5.2	Functional name of contact point	Sperimentazioni Cliniche e Biostat.
B.5.3	Address:
B.5.3.1	Street Address	Via Gattamelata 64
B.5.3.2	Town/ city	Padova
B.5.3.3	Post code	35128
B.5.3.4	Country	Italy
B.5.4	Telephone number	0039-049-8215704
B.5.5	Fax number	0039-049-8215706
B.5.6	E-mail	clinical.trial@ioveneto.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.2.1.2	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	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intraperitoneal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	MITOMYCIN C
D.3.9.4	EV Substance Code	SUB20671
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.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.2.1.2	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	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intraperitoneal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CISPLATIN
D.3.9.1	CAS number	15663-27-1
D.3.9.4	EV Substance Code	SUB07483MIG
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Resectable colorectal carcinomatosis.

Carcinosi colorettale resecabile.

E.1.1.1

Medical condition in easily understood language

Peritoneal carcinomatosis.

Carcinosi peritoneale.

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10050035
E.1.2	Term	Metastatic colon cancer
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Evaluate the role of cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy compared to standard chemotherapy in term of overall survival.

Valutare il ruolo della Chirurgia Cito-Riduttiva+Chemioterapia Ipertermica IntraPeritoneale rispetto alla chemioterapia sistemica, confrontando i due trattamenti in termini di sopravvivenza complessiva.

E.2.2

Secondary objectives of the trial

Evaluate disease-free survival, toxicity of two treatments and their impact on quality of life.

Valutare la sopravvivenza libera da malattia, la tossicità dei due trattamenti e il loro impatto sulla qualità di vita.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Histologically documented colorectal carcinomatosis • Minor/moderate peritoneal carcinomatosis with a Peritoneal Cancer Index (PCI) lower than 20 evaluated by CT and/or PET CT imaging • Patient between age 18 and 75 years. • ECOG 1-2 • ASA score 1-2 • Clinical, instrumental and biohumoral signs of bone marrow, hepatic, renal, pulmonary or cardiac insufficiency absent • Patients must be available for follow up • Signed Informed Consent

• Diagnosi istologica di carcinoma colorettale • Carcinosi peritoneale di lieve/media entità con un Peritoneal Cancer Index (PCI) inferiore a 20 valutato radiologicamente con TAC e/o PET CT. • Età compresa tra 18 e 75 anni • Performance status ECOG 1-2 • ASA score 1-2 • Non segni clinici, strumentali e bioumorali di insufficienza midollare, epatica, renale, polmonare e cardiaca • Disponibilità di sottoporsi a follow-up • Consenso informato scritto

E.4

Principal exclusion criteria

• Extra-peritoneal metastatic localization (retroperitoneum, lymphnodes, liver or lung) • Prior first-line chemotherapy treatment for peritoneal carcinomatosis(adjuvant therapy excluded) • Prior intraperitoneal chemohyperthermic (HIPEC) treatment • Positive history of malignancies for at least 3 years, with the exception of basal cell carcinoma • Evidence of cardiovascular disease (history of congestive heart failure or LVEF <40%) • Evidence of renal disease (creatinine level >1.5 than the normal institutional limits or creatinine clearance <60 mL/min) • Evidence of hepatic disease (ASAT, ALAT, bilirubin >1.5 than the normal institutional limits, PT) • Evidence of hematopoietic disease (WBC <4000/mm3; neutrophil count <1500/mm3; platelets < 80000/mm3) • Evidence of pulomonary disease (BPCO or other restrictive lung disease with FEV1 <50% or a DLCO <40% than the normal limits for age)

• Metastasi a localizzazione extra-peritoneale (retroperitoneo, linfonodi a distanza, fegato e polmone) • Precedente prima linea di chemioterapia sistemica per carcinosi peritoneale (terapie adiuvanti escluse) • Pregresso trattamento chemioipertermico intraperitoneale • Anamnesi positiva per neoplasie negli ultimi tre anni, ad esclusione del carcinoma basocellulare cutaneo • Alterata funzione cardiaca (scompenso cardiaco congestizio pregresso o FE <40%) • Alterata funzione renale (creatinina >1.5 volte il valore normale o creatinina clearance< 60 mL/min). • Alterata funzione epatica (AST, ALT, bilirubina > 1.5 volte il valore normale, PT) • Alterata funzione ematopoietica (leucociti<4000/mm3; neutrofili <1500/mm3;piastrine < 80000/mm3) • Alterata funzione polmonare (BPCO o altri deficit restrittivi polmonari con FEV1 < 50% or a DLCO < 40% del valore normale per età)

E.5 End points

E.5.1

Primary end point(s)

Overall survival from randomization.

Sopravvivenza complessiva dalla randomizzazione.

E.5.1.1

Timepoint(s) of evaluation of this end point

6 years

6 anni

E.5.2

Secondary end point(s)

• Disease-free survival from randomization • Evaluated of treatment toxicity according to the NCI-CTCAE v.4 • Quality of life with EORTC QLQ-C30 and EORTC QLQ-CR29 questionnaires, and HADS Concern Checklist

• Sopravvivenza libera da malattia dalla randomizzazione • Tossicità dei trattamenti valutata in accordo al sistema NCI-CTCAE v.4 • Qualità della Vita valutata con i questionari EORTC QLQ-C30, EORTC QLQ-CR29, HADS e Concern Checklist

E.5.2.1

Timepoint(s) of evaluation of this end point

• Disease-free survival from randomization: 6 years. • Toxicity: until third year. • Quality of life: 1 years.

• Sopravvivenza libera da malattia dalla randomizzazione: 6 anni. • Tossicità: fino a 3 anni. • Qualità di vita: 1 anno.

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.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

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

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:

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

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

122

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)

Standard clinical practice.

Normale pratica clinica.

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

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2013-01-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-01-23

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

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