Clinical Trials Register

Summary
EudraCT Number:	2019-004357-86
Sponsor's Protocol Code Number:	GOIRC-05-2019
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:	2021-08-31
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

2019-004357-86

A.3

Full title of the trial

A Phase II open-label multicentreTrial of first-line Oxaliplatin-based chemotherapy combined with ABP 980 (Biosimilar Trastuzumab) in patients with advanced Gastric or gastro-Esophageal juncTion (GEJ) cancer, HER2-positive

Studio di fase II, in aperto, multicentrico di chemioterapia a base di Oxaliplatino in combinazione con ABP 980 (Trastuzumab biosimilare) in pazienti con adenocarcinoma gastrico o della giunzione gastro-esofagea (GEJ) avanzato, HER2 positivi.

A.3.1

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

Study of chemotherapy combined with ABP 980 in patients with advanced cancer of stomach or gastro-esophageal junction HER2-positive

Studio di chemioterapia associata ad ABP 980 in pazienti con tumore dello stomaco o della giunzione gastro-esofagea avanzato HER2 positivo

A.3.2

Name or abbreviated title of the trial where available

A Phase II study of chemotherapy combined with ABP 980 in patients with advanced Gastric or gastro-E

Studio di fase II di chemioterapia in combinazione con ABP 980 in pazienti con adenocarcinoma gastri

A.4.1

Sponsor's protocol code number

GOIRC-05-2019

A.5.4

Other Identifiers

Name:

TOGETHER

Number:

Acronimo

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	GRUPPO ONCOLOGICO ITALIANO DI RICERCA CLINICA (GOIRC)
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	AMGEN
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	ASST di Cremona
B.5.2	Functional name of contact point	U.O. Oncologia
B.5.3	Address:
B.5.3.1	Street Address	Viale Concordia 1
B.5.3.2	Town/ city	Cremona
B.5.3.3	Post code	26100
B.5.3.4	Country	Italy
B.5.4	Telephone number	+390372408030
B.5.6	E-mail	goirc-together@goirc.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.2.5	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	Kanjinti
D.3.2	Product code	[ABP 980]
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	TRASTUZUMAB
D.3.9.1	CAS number	180288-69-1
D.3.9.2	Current sponsor code	ABP 980
D.3.9.3	Other descriptive name	Biosimilar trastuzumab
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	150
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	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	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

HER2 positive advanced gastric or gastro-esophageal junction cancer

Adenocarcinoma gastrico e della giunzione gastro-esofagea avanzato HER 2 positivo

E.1.1.1

Medical condition in easily understood language

Metastatic tumor of stomach or gastro-esophageal junction

Tumore dello stomaco o della giunzione gastro-esofaea metastatico

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	10001150
E.1.2	Term	Adenocarcinoma gastric
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

To compare PFS in patients receiving an oxaliplatin-based chemotherapy doublet (mFOLFOX6 or XELOX) combined with ABP 980 for HER2+ gastric or gastro-esophageal junction (GEJ) cancer to an historical control.

Comparare la PFS in pazienti che ricevono una doppietta chemioterapica a base di oxaliplatino (mFOLFOX6 o XELOX) associata ad ABP 980 per il trattamento di adenocarcinoma gastrico o della giunzione gastro-esofagea HER2+, rispetto a quella registrata in pazienti riceventi il trattamento standard (controllo storico)

E.2.2

Secondary objectives of the trial

-To determine additional measures of clinical benefit, specifically, OS, TPP duration of response of an oxaliplatin-based chemotherapy doublet (mFOLFOX6 or XELOX) combined with ABP 980 in HER2+ gastric or gastro-esophageal junction (GEJ) cancer patients. It will be performed a comparison with an historical control;
-To compare objective tumor response in term of CR or PR to an historical control;
-To describe safety and QoL of an oxaliplatin-based chemotherapy doublet (mFOLFOX6 or XELOX) combined with ABP 980 in HER2+ gastric or gastro-esophageal junction (GEJ) cancer patients.

Explorative objectives:
-To describe the association between the outcome, experimental factor and sub-factors that may influence the clinical or pathological response (e.g.: sex, age, histological subtype, grading, tumor site, etc.)

- Determinare misure addizionali del beneficio clinico, nello specifico OS, TTP, durata di risposta a una doppietta chemioterapica a base di oxaliplatino (mFOLFOX6 o XELOX) in associazione a ABP 980 nel trattamento di adenocarcinoma gastrico o della giunzione gastro-esofagea HER2+ .
- Comparare la risposta obiettiva tumorale in termini di CR o PR rispetto a un controllo storico;
- Descrivere la sicurezza e qualità della vita del trattamento sperimentale (doppietta chemioterapica a base di oxaliplatino (mFOLFOX6 o XELOX) associato a ABP 980) in pazienti con adenocarcinoma gastrico o della giunzione gastro-esofagea HER2+.

Obiettivi esplorativi:
- Descrivere l’associazione tra outcome, fattori sperimentali principali e secondari che possono influenzare la risposta clinica o patologica (es. sesso, età, sottotipo istologico, grado, localizzazione tumorale, etc.)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Males or females = 18 years old with ECOG performance status (PS) of 0 or 1,
2. Written, signed consent for trial participation must be obtained from the patients appropriately in accordance with applicable ICH guidelines and local and regulatory requirements prior to the performance of any study specific procedures;
3. Histological confirmed diagnosis of GC or GEJ adenocarcinoma
4. Radiolological confirmed locally advanced unresectable or metastatic disease within 28 days prior to the first dose of study treatment
5. Measurable disease according to RECIST 1.1. within 28 days prior the first dose of study treatment. For subjects with only one measurable lesion and prior radiotherapy, the lesion mus be outside the field of prior radiotherapy or must have documented progression following radiation therapy.
6. Tumor HER2 overexpressing, as determined by local testing on a gastric or GEJ tumor specimen. For the purpose of this study, HER-2 overexpression is evaluated with IHC test, followed by ISH when IHC result is equivocal (2+). Positive (3+) or negative (+ or 1+) HER2 IHC results do not require further ISH test.
7. Left ventricular ejection fraction (LVEF) of =55% by 2D echocardiogram

1. Maschi o femmine di età = 18 anni, ECOG Performance Status (PS) di 0 o 1;
2. Modulo di consenso informato firmato e datato, ottenuto dal paziente appropriatamente in accordo alle linee guida ICH e ai requisiti regolatori locali, prima di effettuare qualsiasi procedura studio specifica.
3. Diagnosi di adenocarcinoma gastrico o della giunzione gastro-esofagea istologicamente confermata.
4. Diagnosi di malattia metastatica o localmente avanzata radiologicamente confermata entro 28 giorni precedenti la prima dose della terapia in studio.
5. Malattia misurabile in accordo ai criteri RECIST 1.1 entro 28 giorni precedenti la prima dose della terapia in studio. Per soggetti con una sola lesione misurabile e precedente radioterapia, la lesione deve essere fuori dal campo della precedente radioterapia o deve esserci una documentata progressione successiva alla radioterapia.
6. Iperespressione tumorale di HER2, determinato come da pratica locale su un campione di tessuto tumorale gastrico o della giunzione gastro-esofagea. Per lo scopo di questo studio, la iperespressione di HER2 è valutata tramite test IHC, seguito da ISH qualora i risultati del IHC siano equivoci (2+). Risultati positivi (3+) o negativi (+ o 1+) del test IHC non necessitano di ulteriori test ISH.
7. Frazione di eiezione ventricolare sinistra (LVEF) = 55% valutata tramite ecocardiogramma 2D.

E.4

Principal exclusion criteria

1. Subject has received prior systemic chemotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. However, subject may have received either neo-adjuvant or adjuvant chemotherapy as long as it was completed at least 6 months prior to the first dose of study treatment.
2. Subject has received radiotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma unless the radiotherapy was completed within 28 days prior to start of study treatment. Subject who received palliative radiotherapy to peripheral bone metastases = 14 days prior to start of study treatment and has recovered from all acute toxicities is allowed.
3. Subject has a cardiac dysfunction conditioning a LVEF < 55%;
4. Subject has other significant cardiovascular disease, including:
- Congestive heart failure (defined as New York Heart Association Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, stenting, coronary artery bypass graft, cerebrovascular accident or hypertensive crisis within 6 months prior to administration of first dose of study drug.
- History of clinically significant ventricular arrhythmias (i.e., sustained ventriculal tachycardia, ventricular fibrillation Torsades de Pointes);
- QTc interval > 450 msec
- Cardiac arrhythmias requiring anti-arrhythmic medications (Subject with rate controlled atrial fibrillation for > 1 month prior to first dose of study drugs are eligible)
5. Subject has known peripheral sensory neuropathy > Grade 1 unless the absence of deep tendon reflexes is the sole neurological abnormality.

1. Soggetti che abbiano ricevuto precedenti chemioterapie sistemiche per adenocarcinoma gastrico o della giunzione gastro-esofagea localmente avanzato non resecabile o metastatico. Tuttavia, i soggetti possono aver ricevuto chemioterapia neo-adiuvante o adiuvante, ammesso che sia stata completata almeno entro 6 mesi dalla prima dose del trattamento in studio.
2. Soggetti che abbiano ricevuto radioterapia per adenocarcinoma gastrico o della giunzione gastro-esofagea localmente avanzato non resecabile o metastatico, a meno che la radioterapia non sia stata completata entro 28 giorni dalla prima dose del trattamento in studio. I soggetti che abbiano ricevuto radioterapia palliativa per metastasi ossee = 14 giorni prima dell’inizio del trattamento in studio e che abbiano recuperato da tutte le tossicità acute sono ammessi.
3. Soggetti con disfunzione cardiaca condizionante un LVEF < 55%.
4. Soggetti con altri disturbi cardiovascolari significativi, inclusi:
- Insufficienza cardiaca congestizia (definita dalla New York Association Class III o IV), infarto del miocardio, angina instabile, angioplastica coronarica, stent, bypass coronarico, evento cerebrovascolare o crisi ipertensiva entro i 6 mesi precedenti la prima somministrazione del farmaco in studio.
- Storia di aritmia ventricolare significativa (es. tachicardia ventricolare sostenuta, fibrillazione ventricolare Torsione di Punta).
- Intervallo QTc>450 msec
- Aritmia cardiaca che richieda terapia anti-aritmica (soggetti con fibrillazione atriale controllata da > 1 mese prima della prima dose del farmaco in studio sono eleggibili.)
5. Soggetti con neuropatia sensoriale periferica > Grado 1.

E.5 End points

E.5.1

Primary end point(s)

Progression Free Survival (PFS)

Sopravvivenza libera da progressione (PFS)

E.5.1.1

Timepoint(s) of evaluation of this end point

12 months after enrolling each patient

A 12 mesi dall'arruolamento di ogni paziente

E.5.2

Secondary end point(s)

Overall survival (OS); Time to Progression (TTP); Complete Response (CR) or Partial Response (PR); Duration of Response (DOR); Safety profile; Quality of Life evaluation

Sopravvivenza globale (OS); Tempo di progressione (TTP); Risposta Completa o Risposta Parziale; Durata della risposta (DOR); Profilo di sicurezza; Valutazione della qualità della vita

E.5.2.1

Timepoint(s) of evaluation of this end point

12 months after enrolling each patient; 12 months after enrolling each patient; Every 8 weeks; Every 8 weeks; From Informed consent signature to the end of treatment visit; At the screening, at each cycle of induction phase, at the end of the induction phase, at each cycle of maintenance phase, at the end of treatment, at follow up

A 12 mesi dall'arruolamento di ogni paziente; A 12 mesi dall'arruolamento di ogni paziente; Ogni 8 settimane; Ogni 8 settimane; Dalla firma del consenso informato alla visita di fine trattamento; All'arruolamento, ad ogni ciclo di induzione, al termine dell'induzione, ad ogni ciclo di mantenimento, alla fine del trattamento, al follow up

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

E.8.1.1

Randomised

E.8.1.2

Open

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

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

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

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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 medical care for the condition

Trattamento da 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

2020-07-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-07-17

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

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