Clinical Trials Register

Summary
EudraCT Number:	2020-003440-92
Sponsor's Protocol Code Number:	INFINITY
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:	2021-05-24
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

2020-003440-92

A.3

Full title of the trial

TremelImumab aNd durvalumab combination For the non-operatIve management (NOM) of Microsatellite InstabiliTY (MSI)-high resectable gastric or gastroesophageal junction cancer: The multicentre, single-arm, multi-cohort, Phase II INFINITY study.

Combinazione di tremelimumab e durvalumab finalizzata alla gestione non chirurgica del carcinoma gastrico o gastroesofageo resecabile con elevata istabilità microsatellitare: stduio multicentrico, a singolo braccio, multi-coorte, di fase II INFINITY.

A.3.1

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

Study on the combination of two immunotherapeutic agents as pre-surgical therapy or definitive treatment in patients with resectable gastric or gastroesophageal junction cancer with microsatellite instability.

Studio con la combinazione di due farmaci immunoterapici come terapia prima della chirurgia o come terapia definitiva in pazienti con tumore gastrico o della giunzione gastro-esofagea operabile con instabilità dei microsatelliti.

A.3.2

Name or abbreviated title of the trial where available

Infinity

INFINITY

A.4.1

Sponsor's protocol code number

INFINITY

A.5.4

Other Identifiers

Name:

INFINITY

Number:

INFINITY

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	G.O.N.O. - GRUPPO ONCOLOGICO DEL NORD OVEST
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	Fondazione GONO
B.4.2	Country	Italy
B.4.1	Name of organisation providing support	AstraZeneca S.p.A.
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	Fondazione GONO
B.5.2	Functional name of contact point	Ufficio Sperimentazioni sede operat
B.5.3	Address:
B.5.3.1	Street Address	Via Roma, 67
B.5.3.2	Town/ city	Pisa
B.5.3.3	Post code	56126
B.5.3.4	Country	Italy
B.5.4	Telephone number	+39050992192
B.5.5	Fax number	+39050992069
B.5.6	E-mail	infinitystudy@istitutotumori.mi.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	No
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	Durvalumab
D.3.2	Product code	[MEDI4736]
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	Durvalumab
D.3.9.1	CAS number	1428935-60-7
D.3.9.2	Current sponsor code	Durvalumab
D.3.9.3	Other descriptive name	Durvalumab is a fully human, immunoglobulin G1 kappa monoclonal antibody that selectively blocks the interaction of PD-L1 with PD-1 and CD80. Durvalumab does not induce antibody dependent cell-mediated cytotoxicity (ADCC). Selective blockade of PD-L1/PD-1 and PD-L1/CD80 interactions enhances antitumour immune responses and increases T-cell activation.
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
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.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	No
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	Tremelimumab
D.3.2	Product code	[MEDI1123]
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	Tremelimumab
D.3.9.2	Current sponsor code	Tremelimumab
D.3.9.3	Other descriptive name	Fully human monoclonal antibody against CTLA-4. Immune checkpoint blocker
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
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

The disease under clinical investigation is represented by resectable gastric or gastroesophageal junction (Siewert II-III) adenocarcinoma staged as cT = 2, any cN, or any cT, cN1-3 (TNM classification 8th edition), without distant metastases (cM0).The study requires central confirmation of tumor molecular status of microsatellite instability and dMMR by both immunohistochemistry and multiplex polymerase chain reaction, and EBV-negative status by silver-in situ hybridization.

La malattia oggetto di studio clinico è costituita dall'adenocarcinoma gastrico o della giunzione gastroesofagea (Siewert II-III) resecabile, stadiato clinicamente secondo la classificazione TNM (8° edizione) come cT = 2, ogni cN, oppure ogni cT, cN1-3, senza evidenza di metastasi a distanza (cM0). E' necessaria conferma centralizzata di instabilità microsatellitare mediante immunoistochimica e reazione polimerasica a catena, e status EBV-negativo mediante ibridizzazione in situ argentica.

E.1.1.1

Medical condition in easily understood language

Cancer in the stomach or in the junction between the stomach and the oesophagus, without metastases in other organs and surgically resectable, with microsatellite instability and no EBV infection.

Tumore nello stomaco o nella giunzione tra stomaco ed esofago, senza metastasi in altri organi e asportabile chirurgicamente, con instabilità dei microsatelliti e assenza di infezione da EBV.

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	LLT
E.1.2	Classification code	10073379
E.1.2	Term	Tubular adenocarcinoma gastric
E.1.2	System Organ Class	100000004864

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10073378
E.1.2	Term	Signet-ring cell adenocarcinoma 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

To assess the activity of the immunotherapy combination of tremelimumab plus durvalumab as neoadjuvant (cohort 1) or definitive (cohort 2) treatment of resectable microsatellite instability (MSI)-high gastric cancer.

Valutare l’attività della combinazione di farmaci immunoterapici tremelimumab e durvalumab in qualità di trattamento neoadiuvante (coorte 1) o definitivo (coorte 2) per il tumore gastrico o della giunzione gastroesofagea con instabilità microsatellitare e resecabile.

E.2.2

Secondary objectives of the trial

To assess the impact of immunotherapy combination of tremelimumab plus durvalumab on patients’ quality of life in the neoadjuvant (cohort 1) or potentially definitive (cohort 2) treatment setting.
To assess the efficacy of immunotherapy combination of tremelimumab plus durvalumab in terms of disease-free survival and overall survival in the neoadjuvant setting (cohort 1) and in the non-operative management setting (cohort 2).
To assess the impact of immunotherapy combination of tremelimumab plus durvalumab on gastrectomy-free survival in the non-operative management setting (cohort 2).
To assess the safety of immunotherapy combination of tremelimumab plus durvalumab in the neoadjuvant (coorte 1) and in the non-operative management setting (cohort 2).
To conduct exploratory translational analyses aimed at identifying which subgroup of patients may derive the highest chance of definitive cure from immunotherapy combination of tremelimumab plus durvalumab (cohort 1 and 2).

Valutare l’impatto della combinazione di tremelimumab e durvalumab sulla qualità di vita dei pazienti nell'ambito del trattamento neoadiuvante (coorte 1) o potenzialmente definitivo (coorte 2).
Valutare l’efficacia della combinazione di tremelimumab e durvalumab in termini di sopravvivenza libera da malattia e globale nell'ambito del trattamento neoadiuvante (coorte 1) o della gestione non operatoria (coorte 2).
Valutare l’impatto della combinazione di tremelimumab e durvalumab sulla sulla sopravvivenza libera da gastrectomia nei pazienti seguiti nell’ambito della gestione non operatoria (coorte 2).
Valutare il profilo di tollerabilità della combinazione di tremelimumab e durvalumab nell'ambito neoadiuvante (coorte 1) o della gestione non operatoria (coorte 2).
Condurre analisi esploratorie di carattere traslazionale mirate ad individuare un sottogruppo di pazienti che possa trarre il massimo beneficio in termini di eradicazione completa di malattia dopo trattamento (coorte 1 e 2)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent and any locally required authorization (such as the European Union [EU] Data Privacy Directive) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
2. Age = 18 years old.
3. ECOG Performance Status 0-1.
4. Body weight >30 kg.
5. Diagnosis of resectable gastric or gastroesophageal junction (Siewert II-III) cancer, categorized according to TNM classification 8th edition:
• cT = 2, any cN, M0
• Any cT, cN1-3, M0
6. Absence of distant metastases as defined by negativity of computed tomography (CT) and 18-fluorodeoxyglucose positron-emission tomography (18-FDG PET).
7. Life expectancy of at least 12 weeks
8. MSI-high and dMMR status confirmed by IHC and multiplex PCR, and EBV-negative status by ISH, as determined centrally at the Co-ordinating Centre.
9. Adequate bone marrow and organ function, as defined by laboratory tests:
a. Neutrophil count = 1.5 x 103/µL
b. Platelet count = 100 x 106/µL
c. Haemoglobin = 9 g/dL
d. Total bilirubin lower than 1.5 time the upper-normal limits (ULN) of the Institutional normal values
e. AST (SGOT) and/or ALT (SGPT) < 2.5 x ULN
f. Creatinine clearance (calculated according to Cockroft and Gault) > 40 mL/min or serum creatinine < 1.5 x ULN.

1. Consenso informato alle procedure dello studio e alle analisi molecolari.
2. Età = 18 anni.
3. ECOG Performance Status 0-1.
4. Peso corporeo >30 kg.
5. Diagnosi di carcinoma dello stomaco o della giunzione gastro-esofagea (Siewert II-III), definito secondo la classificazione TNM 8th edizione:
cT = 2, ogni cN, M0 oppure ogni cT, cN1-3, M0
6. Assenza di metastasi a distanza, sulla base della negatività alla TAC torace-addome-pelvi e 18-FDG PET.
7. Aspettativa di vita di almeno 12 settimane.
8. Positività per instabilità microsatellitare e dello status di deficit del mismatch repair confermata con immunoistochimica e PCR, e negatività per EBV con ibridazione in situ, determinate centralmente presso il Centro Coordinatore.
9. Adeguata funzionalità d’organo, definita dai test di laboratorio:
a. Neutrofili = 1.5 x 103/µL
b. Piastrine = 100 x 106/µL
c. Emoglobina = 9 g/dL
d. Bilirubina totale < 1.5 volte il limite superiore del valore normale (ULN)
e. AST (SGOT) e/o ALT (SGPT) < 2.5 x ULN
f. Clearance della creatinina (calcolata secondo l’equazione di Cockroft and Gault) > 40 mL/min or creatinine sierica < 1.5 x ULN.

E.4

Principal exclusion criteria

1. Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site)
2. Previous enrolment in the present study
3. Participation in another clinical study with an investigational product during the last 12 months
4. Signs of distant metastases.
5. Prior medical treatments or irradiation for gastric cancer.
6. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
7. Previous treatments with immune checkpoint inhibitors targeting CTLA4, including tremelimumab, PD-1 or PD-L1, including durvalumab.
8. History of allergy or severe hypersensitivity reaction to monoclonal antibodies.
9. History of autoimmune diseases or history of organ transplantation that require immunosuppressive therapy. The following are exceptions to this criterion:
• Patients with vitiligo or alopecia

• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement

• Any chronic skin condition that does not require systemic therapy

• Patients with celiac disease controlled by diet alone
10. History of active primary immunodeficiency Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA
11. Any condition requiring systemic treatment with corticosteroids at doses equal or superior to 10 mg daily of prednisone or equivalents, or other immunosuppressive drugs within 14 days from the inclusion in the study. The following medications are exceptions to this criterion:
• Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra-articular injection)

• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent

• Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
12. Administration of live vaccines within 4 weeks from the inclusion in the study. Note: Patients, if enrolled, should not receive live vaccine while receiving study drug(s) and up to 30 days after the last dose of study drug(s).
13. History of allogenic organ transplantation
14. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
15. Women in pregnancy or lactation condition. Women with child-bearing potential or sexually-active men not willing to use adequate contraception during the whole study period.
16. Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.

1. Partecipazione in un altro trial clinico con farmaci sperimentali negli ultimi 12 mesi.
2. Metastasi a distanza.
3. Precedenti trattamenti medici o radianti per il tumore gastrico.
4. Interventi di chirurgia maggiore entro 28 giorni dalla prima dose di farmaco da studio.
5. Precedenti trattamenti con immune checkpoint inhibitors diretti contro CTLA4, tra cui tremelimumab, PD-1 o PD-L1, fra i quali durvalumab.
6. Anamnesi di allergia o reazione severa di ipersensibilità ad anticorpi monoclonali.
7. Anamnesi positiva per malattie autoimmuni o trapianto d’organo con necessità di terapia immunosoppressiva, con le seguenti eccezioni: vitiligine o alopecia, ipotiroidismo (es. sindrome di Hashimoto) stabile con la terapia ormonale sostitutiva, celiachia controllata unicamente con la dieta, e ogni condizione patologica della cute che non richieda una terapia sistemica.
8. Immunodeficienza primaria, infezioni attive tra cui la tubercolosi (valutazione clinica che comprenda l’anamnesi, l’esame obiettivo e i dati radiologici, unitamente al test effettuato secondo le linee guida di pratica clinica locali), epatite B (nota positività per l’antigene di superficie di HBV, cioè HBsAg), epatite C. Pazienti con una pregressa o risolta infezione da HBV (definita come la presenza di anticorpi anti core, anti-HBc, e assenza di HBsAg) sono eleggibili per lo studio, mentre pazienti con la positività per gli anticorpi contro HCV sono eleggibili solo in caso di negatività per l’HCV RNA.
9. Ogni condizione che richieda un trattamento sistemico con corticosteroidi a dosi uguali o superiori a 10 mg di prednisone al giorno o equivalenti, oppure altri farmaci immunosoppressivi entro 14 giorni dall’inclusione nello studio. È consentito l’uso di: steroidi topici, intranasali, inalatori o in iniezioni locali (es. intrarticolari), corticosteroidi per via sistemica a dosi inferiori a 10 mg al giorno di prednisone o equivalenti, steroidi come premedicazione per reazioni di ipersensibilità (es. premedicazione per effettuazione di TAC)
10. Somministrazione di vaccini vivi entro 4 settimane dall’inclusione nello studio. Nota: In caso di arruolamento nello studio, i pazienti non dovranno ricevere vaccini vivi per tutta la durata del trattamento e fino a 30 giorni dalla somministrazione dell’ultima dose di farmaco/i.
11. Presenza di malattie intercorrenti non adeguatamente controllate, tra cui infezioni attive o in corso, scompenso cardiaco sintomatico, ipertensione non controllata, angina pectoris instabile, aritmia cardiaca, interstiziopatia polmonare, malattie croniche gastrointestinali associate a diarrea, oppure patologie psichiatriche o situazioni sociali che limiterebbero l’aderenza alle procedure dello studio, oppure incrementerebbero sostanzialmente il rischio di incidenza di eventi avversi o comprometterebbero la capacità del paziente di fornire il proprio consenso informato scritto.
12. Donne in stato di gravidanza o in corso di allattamento. Donne fertili o uomini sessualmente attivi che rifiutino di utilizzare adeguati metodi contraccettivi durante l’intero periodo di studio.
13. Concomitante arruolamento in un altro studio clinico, a meno che sia uno studio clinico osservazionale (non interventistico) oppure in corso di follow up in uno studio interventistico.

E.5 End points

E.5.1

Primary end point(s)

Cohort 1: Pathological complete response (ypT0N0) and negative ctDNA status after neoadjuvant immunotherapy in the intention-to-treat population.
Cohort 2: 2-year complete response rate, defined as the absence of macroscopic or microscopic residual disease (locally, regionally and distantly) at radiological examinations, tissue and liquid biopsy, in absence of salvage gastrectomy.

Coorte 1: Risposta patologica completa (ypT0N0), definita come assenza di cellule tumorali vitali nel tessuto asportato durante l’intervento chirurgico, nella popolazione intention-to-treat, associata alla negatività della biopsia liquida (assenza di DNA tumorale circolante).
Coorte 2: Tasso di risposta clinica completa a 2 anni, definita come assenza di malattia macroscopica o microscopica residua (locale, regionale e a distanza) a livello radiologico, tissutale e di biopsia liquida, senza ricorrere all’intervento di gastrectomia di salvataggio.

E.5.1.1

Timepoint(s) of evaluation of this end point

Cohort 1: 18 months
Cohort 2: 30 months

Coorte 1: 18 mesi
Coorte 2: 30 mesi

E.5.2

Secondary end point(s)

Patient reported outcomes (completion of quality of life questionnaires, European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-STO-22 and EuroQol EQ-5D, during the treatment phase).
3-year disease-free survival.
5-year overall survival.
Metastases-free survival.
Gastrectomy-free survival, defined as time from the inclusion in the study to the occurrence of gastrectomy or death from any cause (cohort 2 only).
Treatment safety (incidence of adverse events during the treatment and follow-up phases, assessed according to CTCAE v5.0);
Morbidity and mortality of gastrectomy following tremelimumab and durvalumab as pre-operative treatment strategy (cohort 1 only).

Patient reported outcomes (attraverso il completamento dei questionari di qualità di vita: European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-STO-22 e EuroQol EQ-5D, durante la fase di trattamento).
Sopravvivenza libera da malattia a 3 anni.
Sopravvivenza globale a 5 anni.
Sopravvivenza libera da metastasi.
Sopravvivenza libera da gastrectomia, definita come tempo intercorso tra l’inclusione nello studio e la gastrectomia o la morte per ogni causa (solo coorte 2).
Tasso di tossicità complessiva (incidenza di eventi avversi durante la fase di trattamento e/o di follow up, secondo la classificazione CTCAE v5.0);
Tasso di morbidità e di mortalità dell’intervento di gastrectomia dopo il regime di trattamento pre-operatorio con tremelimumab e durvalumab (solo coorte 1).

E.5.2.1

Timepoint(s) of evaluation of this end point

quality of life, safety, surgical morbidity/morality: 24 months.
survival endpoints: 36-60 months.

qualità di vita, tossicità e morbilità/mortalità chirurgica: 24 mesi.
endpoint di sopravvivenza: 36-60 mesi.

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)

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

Yes

E.8.1.7.1

Other trial design description

studio a singolo braccio

single arm study

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)

Subjects with disease relapse during follow-up will be followed for survival. Subjects without disease relapse after 2 years of follow-up will be followed for disease relapse and for survival until at least 5 years or more.

I soggetti con recidiva di malattia durante il follow-up verranno seguiti per la sopravvivenza. I soggetti senza recidiva di malattia dopo 2 anni di follow-up verranno seguiti per la recidiva e per la sopravvivenza fino ed eventualmente oltre 5 anni complessivi.

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

2020-12-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-12-21

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

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IMP with orphan designation in the indication
Orphan Designation Number:
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