Clinical Trials Register

Summary
EudraCT Number:	2019-001478-27
Sponsor's Protocol Code Number:	IRFMN-GCC-7813
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-06-15
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

2019-001478-27

A.3

Full title of the trial

Prophylactic surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC CO2) versus standard surgery in gastric carcinoma at high risk of peritoneal carcinomatosis. Short and long-term outcomes. A collaborative randomized controlled trial of: ACOI, FONDAZIONE AIOM, SIC, SICE, SICO. GOETH STUDY

Chirurgia profilattica e chemioterapia ipertermica intraperitoneale (HIPEC CO2) verso chirurgia standard in pazienti affetti da tumore gastrico ad alto rischio di sviluppare carcinosi peritoneale. Risultati a breve e lungo termine. Uno studio collaborativo randomizzato controllato di ACOI, Fondazione AIOM, SIC, SICE, SICO. Studio GOETH

A.3.1

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

Prophylactic surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC CO2) versus standard surgery in gastric carcinoma at high risk of peritoneal carcinomatosis.

Chirurgia profilattica e chemioterapia ipertermica intraperitoneale (HIPEC CO2) verso chirurgia standard in pazienti affetti da tumore gastrico ad alto rischio di sviluppare carcinosi peritoneale.

A.3.2

Name or abbreviated title of the trial where available

GOETH STUDY

A.4.1

Sponsor's protocol code number

IRFMN-GCC-7813

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	Associazione Chirurghi Ospedalieri Italiani
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	ACTA 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	Istituto di Ricerche Farmacologiche Mario Negri IRCCS
B.5.2	Functional name of contact point	Servizio Informazione sulla Sperime
B.5.3	Address:
B.5.3.1	Street Address	Via La Masa 19
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20156
B.5.3.4	Country	Italy
B.5.4	Telephone number	0239014684
B.5.5	Fax number	0233200231
B.5.6	E-mail	erica.rulli@marionegri.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.3.1	Product name	MITOMICINA
D.3.2	Product code	[L01DC03]
D.3.4	Pharmaceutical form	Powder and solvent 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	MITOMICINA
D.3.9.2	Current sponsor code	NA
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	15
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.2.5	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	Cisplatin
D.3.2	Product code	[L01XA01]
D.3.4	Pharmaceutical form	Powder and solvent 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	CISPLATINO
D.3.9.2	Current sponsor code	NA
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.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

Patients with gastric carcinoma at high risk of developing peritoneal carcinomatosis, suitable to radical surgery.

Pazienti con tumore gastrico ad alto rischio di carcinomatosi peritoneale candidabili a chirurgia radicale.

E.1.1.1

Medical condition in easily understood language

Patients with gastric carcinoma at high risk of developing peritoneal carcinomatosis, suitable to radical surgery.

Pazienti con tumore gastrico ad alto rischio di carcinomatosi peritoneale candidabili a chirurgia radicale.

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	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10007350
E.1.2	Term	Carcinoma gastric
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

The primary objective of the study is to compare the efficacy of prophylactic surgery (radical gastric resection, appendectomy, round ligament of the liver resection and bilateral adnexectomy) plus HIPEC CO2 versus standard surgery in terms of disease free survival.

L’obiettivo primario dello studio è valutare l’efficacia della chirurgia profilattica (resezione gastrica radicale, appendicectomia, resezione del legamento rotondo del fegato e annessiectomia bilaterale) con HIPEC CO2 rispetto alla chirurgia standard in termini di sopravvivenza libera dalla malattia (DFS).

E.2.2

Secondary objectives of the trial

The secondary objective is to compare the safety profile of prophylactic surgery plus HIPEC CO2 vs. standard surgery alone.

L’obiettivo secondario è valutare il profilo di sicurezza della chirurgia con HIPEC CO2 rispetto alla sola chirurgia.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients with histologically documented gastric carcinoma (diffuse/intestinal histotype) eligibile for R0:
a) Presurgical or intraoperative stage T3-T4 N0-N+ primary tumour (TNM 8 th).
b) Urgent presentation: perforation without purulent generalized peritonitis
c) Positive cytology of peritoneal fluid (if previously obtained)
2. Age = 18 years and =75 years.
3. Written informed consent.

1. Pazienti con tumore gastrico (diffuso/ istotipo intestinale) eligibili per R0 documentato tramite esame istologico:
a) Tumore primario T3-T4 N0-N+ pre chirurgico o intraoperatorio.
b) Presentazione in urgenza: perforazione senza evidenza di peritonite purulenta generalizzata
c) Citologia del liquido peritoneale positiva (se precedentemente ottenuta)

2. Età compresa tra i 18 e 75 anni inclusi
3. Consenso informato scritto

E.4

Principal exclusion criteria

1. Gastroesophageal Junction (GEJ) cancer
2. Distant metastatic disease (even if limited and completely resected)
3. Peritoneal carcinomatosis
4. History of tumour diagnosed in the 3 years before entering the study, except for topical and healed pathologies that do not need further treatment (e.g. non-melanoma skin carcinomas, superficial bladder carcinomas or in situ carcinoma of the breast or cervix).
5. Psychological, family or social conditions which may negatively affect the treatment and follow-up protocol.
6. Poor general conditions (ECOG > 2).
7. Impaired cardiac function (history of congestive heart failure or FE <40%). Clinically significant cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrolment), unstable angina, congestive heart failure (New York Heart Association Classification Class > II) or serious uncontrolled cardiac Arrhythmia requiring medication
8. Impaired renal function (creatinine> 1.5 upper limit of normal or creatinine clearance <60 mL / min).
9. Impaired hepatic function (AST, ALT >2.5 upper limit of normal, bilirubin > 1.5 upper limit of normal).
10. Impaired hematopoietic function (leucocytes <4000 / mm3, neutrophils <1500 / mm 3, platelets <100000 / mm3).
11. Impaired pulmonary function (presence of COPD or other pulmonary restrictive conditions with FEV1 <50% or DLCO <40% of normal age value).
12. History or presence of other disease, metabolic dysfunction, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of HIPEC or chemotherapy or patient at high risk from treatment complications.
13. Pregnancy.
14. Krukenberg tumor
15. Refusal to join the study.

1. Tumore della giunzione gastroesofagea (GEJ)
2. Metastasi a distanza (anche se limitate e completamente resecate)
3. Carcinosi peritoneale
4. Storia di tumore diagnosticato nei 3 anni precedenti l’entrata in studio, ad eccezione di tumori topici e guariti che non hanno necessitato di ulteriore trattamento (es. carcinoma della pelle non-melanoma, carcinoma superficiale della vescica o carcinoma in sito del seno o cervice).
5. Condizioni psicologiche, famigliari o sociali che potrebbero condizionare negativamente il trattamento o il follow-up del protocollo
6. Condizioni generali scadenti (ECOG >2)
7. Funzione cardiaca compromessa (storia di insufficienza cardiaca congestizia o FE <40%). Malattia cardiovascolare clinicamente significativa: ictus cerebrale (<6 mesi prima dell'arruolamento), infarto miocardico (<6 mesi prima dell'arruolamento), angina instabile, insufficienza cardiaca congestizia (Classe di classificazione New York Heart Association > II o aritmia cardiaca grave non controllata richiedendo farmaci.
8. Funzionalità renale compromessa (creatinina> 1,5 limite superiore della clearance normale o della creatinina <60 ml / min)
9. Compromissione della funzionalità epatica (AST, ALT> 2,5 limite superiore del normale, bilirubina> 1,5 limite superiore del normale)
10. Funzione ematopoietica alterata (leucociti <4000 / mm3, neutrofili <1500 / mm3, piastrine <100000 / mm3)
11. Funzione polmonare compromessa (presenza di BPCO o altre condizioni restrittive polmonari con FEV1 <50% o DLCO <40% del valore normale dell'età).
12. Anamnesi o presenza di altre malattie, disfunzioni metaboliche o reperti clinici di laboratorio che forniscano il ragionevole sospetto di una malattia o di una condizione che controindica l'uso di HIPEC o chemioterapia o paziente ad alto rischio per complicanze del trattamento.
13. Gravidanza
14. Tumore di Krukenberg
15. Rifiuto di aderire allo studio

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is DFS defined as the time from randomization to the date of first local relapse or distant relapse or peritoneal carcinomatosis or death for any cause, whichever comes first.
The secondary efficacy endpoints are: Overall Survival (OS) defined as the time from randomization to the death for any cause, and Local recurrence free survival (LRFS) defined as the time from randomization to the date of first local relapse, peritoneal carcinomatosis or death for any cause, whichever comes first

L’indicatore primario di efficacia è la DFS definita come il tempo dalla randomizzazione alla data del primo evento tra ricaduta a distanza, ricaduta locale, carcinosi peritoneale o morte per ogni causa.
Gli indicatori secondari di efficacia sono: la sopravvivenza generale (OS) definita come il tempo dalla data di randomizzazione alla data di morte per qualsiasi causa e il tempo libero da ricaduta locale (LRFS) definito come il tempo dalla data di random alla data del primo evento tra ricaduta locale, carcinosi peritoneale, o morte per ogni causa.

E.5.1.1

Timepoint(s) of evaluation of this end point

6 years

6 anni

E.5.2

Secondary end point(s)

The safety endpoints will be:
- mortality at 30 and 90 days from surgery
- morbidity evaluated during and after surgery, graded according to the NCI-CTAE version 4.03 for AE related to chemotherapy and according to Clavien Dindo for surgery complications
- number of post-surgery complication
- duration of surgery
- length of hospitalization
- number of patients performing the adjuvant chemotherapy.

Gli indicatori della sicurezza saranno:
- mortalità a 30 e 90 giorni dalla chirurgia
- morbidità durante e dopo la chirurgia valutata in accordo alla classificazione NCI-CTAE 4.03 per le tossicità relative alla chemioterapia HIPEC e in accordo alla scala Clavien Dindo per le complicazioni chirurgiche.
- numero di complicazioni post chirurgia
- durata della chirurgia
- lunghezza dell’ospedalizzazione
- numero di pazienti che faranno la chemioterapia adiuvante

E.5.2.1

Timepoint(s) of evaluation of this end point

6 years

6 anni

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

E.6.4

Safety

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)

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

chirurgia standard

standard surgery

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

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

scheduled events reached

Raggiungimento degli eventi attesi

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:

120

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

120

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

240

F.4.2

For a multinational trial

F.4.2.1

In the EEA

240

F.4.2.2

In the whole clinical trial

240

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)

Clinical practice

Pratica clinica

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

2019-09-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-07-18

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

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