Clinical Trials Register

Summary
EudraCT Number:	2016-004394-40
Sponsor's Protocol Code Number:	TRIPLETE
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-09-10
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

2016-004394-40

A.3

Full title of the trial

Randomized phase III study of triplet mFOLFOXIRI plus PANITUMUMAB versus mFOLFOX6 plus PANITUMUMAB as initial therapy for unresectable RAS and BRAF wild-type metastatic colorectal cancer patients

Studio di fase III randomizzato con tripletta mFOLFOX IRI più panitumumab verso mFOLFOX6 più panitmumab come prima linea di terapia in pazienti con carcinoma colorettale metastatico inoperabile RAS e BRAF wild-type.

A.3.1

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

FOLFOXIRI plus Panitumumab or FOLFOX plus Panitumumab in the treatment of metastatic colorectal cancer.

folfoxiri più panitumumab contro folfox più panitumumab nel carcinoma del colonretto metastatico.

A.3.2

Name or abbreviated title of the trial where available

TRIPLETE

A.4.1

Sponsor's protocol code number

TRIPLETE

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	Fondazione GONO
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	Italy
B.4.1	Name of organisation providing support	G.O.N.O.
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	G.O.N.O. - GRUPPO ONCOLOGICO DEL NORD OVEST
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	tripletestudy@gmail.com

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	VECTIBIX - 20 MG/ML CONCENTRATO PER SOLUZIONE PER INFUSIONE - USO ENDOVENOSO 1 FLACONCINO (VETRO) 20 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	AMGEN EUROPE B.V.
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	Panitumumab
D.3.2	Product code	[Panitumumab]
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	PANITUMUMAB
D.3.9.1	CAS number	339177-26-3
D.3.9.2	Current sponsor code	Panitumumab
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	Yes
D.3.11.13.1	Other medicinal product type	Ab monoclonale prodotto da DNA ricombinante
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	FLUOROURACILE AHCL - 50MG/ML SOLUZIONE INIETTABILE O INFUSIONE 1 FLACONCINO IN VETRO DA 100 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	ACCORD HEALTHCARE LIMITED
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	Fluorouracile
D.3.2	Product code	[Fluorouracile]
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	5 Fluorouracile
D.3.9.1	CAS number	51-21-8
D.3.9.2	Current sponsor code	5 Fluorouracile
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	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	OXALIPLATINO ACCORD - 5 MG/ML CONCENTRATO PER SOLUZIONE PER INFUSIONE 1 FLACONCINO IN VETRO DA 40 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	Oxaliplatino
D.3.2	Product code	[Oxaliplatino]
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	OXALIPLATINO
D.3.9.1	CAS number	63121-00-6
D.3.9.2	Current sponsor code	Oxaliplatino
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	5
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: 4
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	CALCIO LEVOFOLINATO TEVA - 25 MG POLVERE PER SOLUZIONE INIETTABILE 1 FLACONCINO
D.2.1.1.2	Name of the Marketing Authorisation holder	TEVA 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	Calcio Levofolinato
D.3.2	Product code	[Calcio Levofolinato]
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	CALCIO LEVOFOLINATO
D.3.9.1	CAS number	80433-71-2
D.3.9.2	Current sponsor code	Calcio levofolinato
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	25
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: 5
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	IRINOTECAN CSC - 20 MG/ML CONCENTRATO PER SOLUZIONE PER INFUSIONE 1 FLACONCINO IN VETRO DA 15 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	CSC PHARMACEUTICALS HANDELS 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	Irinotecan
D.3.2	Product code	[Irinotecan]
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	Irinotecan
D.3.9.1	CAS number	100286-90-6
D.3.9.2	Current sponsor code	Irinotecan
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	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

Metastatic Colorectal Cancer

Carcinoma Colorettale metastatico

E.1.1.1

Medical condition in easily understood language

colorectal cancer spread at distance

tumore al colon retto diffuso a distanza

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	10052362
E.1.2	Term	Metastatic colorectal 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

compare the activity of panitumumab in combination with mFOLFOX6 or with mFOLFOXIRI in RAS and BRAF wt mCRC patients in terms of Overall Response Rate according to RECIST version 1.1

Distribuzione del tasso di risposte complessive (ORR)

E.2.2

Secondary objectives of the trial

Safety profile;
Duration of Progression-free Survival (PFS);
Duration of Overall Survival (OS);
Centrally assessed ORR;
Distribution of Early Tumour Shrinkage (ETS);
Deepness of response (DoR)
R0 Resection Rate
Translational analyses

Profilo di tossicità; Durata della sopravvivenza complessiva (OS); Durata della sopravvivenza libera da progressione (PFS); Valutazione centralizzata dell' ORR; Distribuzione dell'Early Tumour Shrinkage (ETS); Profondità della risposta (DoR); Tasso di resezioni secondarie R0; Analisi traslazionali.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Histologically proven diagnosis of colorectal cancer.
Initially unresectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease.
At least one measurable lesion according to RECIST1.1
Availability of a tissue tumour sample (primary tumour and/or metastatic sites)
Previous adjuvant chemotherapy allowed only if with fluoropyrimidine monotherapy and more than 6 months elapsed between the end of adjuvant and first relapse.
RAS (codons 12, 13, 59, 61, 117 and 146 of KRAS and NRAS genes) and BRAF (V600E mutation) wild type status of primary colorectal cancer or related metastasis (local or central laboratory assessment).

Tumore del colon-retto metastatico inizialmente non resecabile non precedentemente trattato per la malattia metastatica.
Almeno una lesione misurabile in base ai criteri RECIST1.1.
Disponibilità del campione tumorale (primitivo e/o metastasi).
Una precedente chemioterapia adiuvante con fluoropirimidine in monoterapia è permessa se sono trascorsi almeno 6 mesi tra la fine dell’adiuvante e la prima recidiva.
Stato di RAS (codoni 12, 13, 59, 61, 117 e 146 dei geni KRAS e NRAS) e BRAF (mutazione V600E) non mutato del tumore primitivo o delle metastasi.

E.4

Principal exclusion criteria

Previous treatment for metastatic disease.
Radiotherapy to any site within 4 weeks before the study.
Previous adjuvant oxaliplatin-containing chemotherapy.
Previous treatment with EGFR inhibitors.
Untreated brain metastases or spinal cord compression or primary brain tumours.
Symptomatic peripheral neuropathy > 1 grade NCIC-CTG criteria.
Diagnosis of interstitial pneumonitis or pulmonary fibrosis.

Precedente trattamento per malattia metastatica.
Trattamento radioterapico in qualunque sede nelle 4 settimane precedenti lo studio.
Precedente chemioterapia adiuvante contenente oxaliplatino.
Precedente trattamento con inibitori di EGFR.
Metastasi cerebrali non trattate o compressione midollare o tumori cerebrali primitivi.
Neuropatia periferica sintomatica di grado > 1 secondo i criteri NCIC-CTG.
Diagnosi di polmonite interstiziale o fibrosi polmonare.

E.5 End points

E.5.1

Primary end point(s)

Distribution of overall response rate (ORR)
ORR is defined as the percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria, during the induction and the maintenance phases of treatment. The determination of clinical response will be based on investigator reported measurements. Responses will be evaluated every 8 weeks.

Distribuzione del tasso di risposte complessive (ORR).
Il tasso di risposte obiettive (ORR) è definito come la Percentuale di pazienti, relativa al totale dei soggetti arruolati che ottengono una risposta completa (CR) o parziale (PR), in base ai criteri RECIST 1.1, durante le fasi di induzione e di mantenimento. La determinazione della risposta clinica sarà basata sulle misure riportate dallo sperimentatore. Le risposte saranno valutate ogni 8 settimane.

E.5.1.1

Timepoint(s) of evaluation of this end point

48 months

48 mesi

E.5.2

Secondary end point(s)

Safety profile.
Overall Toxicity Rate is defined as the percentage of patients, relative to the total of enrolled subjects, experiencing any adverse event, according to National Cancer Institute Common Toxicity Criteria (version 4.0), during the induction and the maintenance phases of treatment.; Duration of Overall Survival (OS).
Overall survival (OS) is defined as the time from randomization to the date of death due to any cause. For patients still alive at the time of analysis, the OS time will be censored on the last date the patients were known to be alive.; Duration of Progression-free Survival (PFS).
Progression Free Survival (PFS) is defined as the time from randomization to the first documentation of objective disease progression or death due to any cause, whichever occurs first. Documentation of disease progressive disease is defined as per RECIST 1.1 criteria based on investigator assessment. PFS will be censored on the date of the last evaluable on study tumour assessment documenting absence of progressive disease for patients who are alive, on study and progression free at the time of the analysis. Alive patients having no tumour assessments after baseline will have time to event censored on the date of randomization.; Centrally assessed ORR.
Centrally assessed ORR is defined as the percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria, during the induction and the maintenance phases of treatment. The determination of clinical response will be based on central re-evaluation of CT scan images.; Early Tumour Shrinkage Rate (ETS) is defined as the percentage of patients, relative to the total of the enrolled subjects, achieving a =20% decrease in the sum of diameters of RECIST target lesions at week 8 compared to baseline.; Deepness of response (DoR).
Deepness of Response (DoR) is defined as the relative change in the sum of longest diameters of RECIST target lesions at the nadir, in the absence of new lesions or progression of non-target lesions, when compared with baseline.; R0 Resection Rate.
R0 Resection Rate is defined as the percentage of patients, relative to the total of enrolled subjects, undergoing secondary R0 resection of metastases. Secondary R0 surgery is defined as microscopically margin free complete surgical removal of all residual disease, performed during treatment or after its completion, allowed by tumoral shrinkage and/or disappearance of one or more lesions.; Translational analyses.

Profilo di tossicità. Il tasso di tossicità complessiva è definito come la percentuale di pazienti, relativo al totale dei soggetti arruolati che ricevono almeno una dose del trattamento, che evidenziano un qualsiasi evento avverso, in base ai National Cancer Institute Common Toxicity Criteria (version 4.0), durante le fasi di induzione e di mantenimento.
; Durata della sopravvivenza complessiva (OS).
La sopravvivenza complessiva (OS) è definita come il tempo dalla randomizzazione alla data di morte per qualsiasi causa. Per i pazienti ancora vivi al tempo dell'analisi, la sopravvivenza complessiva sarà censorizzata all'ultima data in cui il paziente risulterà vivo.
; Durata della sopravvivenza libera da progressione (PFS).
La sopravvivenza libera da progressione (PFS) è definita come il tempo dalla randomizzazione alla prima evidenza di progressione obiettiva della malattia o morte del paziente per qualsiasi causa, a seconda di quale si verifichi prima. La determinazione di progressione di malattia sarà basata sulle misurazioni riportate dallo sperimentatore. La risposta obiettiva di malattia sarà valutata secondo i criteri RECIST 1.1. La PFS sarà censorizzata (misurata?)alla data dell'ultima valutazione che documenta l'assenza di progressione di malattia per i pazienti in studio e liberi da progressione al tempo dell'analisi. I pazienti vivi che non hanno una valutazione tumorale dopo il basale saranno censorizzati alla data di randomizzazione.; Valutazione centralizzata dell' ORR.
La valutazione centralizzata dell'ORR è definita come la percentuale di pazienti, relativa al totale dei soggetti arruolati che ottengono una risposta completa (CR) o parziale (PR), in base ai criteri RECIST 1.1, durante le fasi di induzione e di mantenimento. La determinazione della risposta clinica sarà basata sulla rivalutazione centralizzata delle immagini TAC.; Distribuzione dell'Early Tumour Shrinkage (ETS).
L'Early Tumour Shrinkage (ETS) è definita come la percentuale di pazienti, relativa al totale dei soggetti arruolati, che ottengono una riduzione della somma dei diametri delle lesioni target RECIST =20% a 8 settimane rispetto al basale.; Profondità della risposta (DoR).
La profondità della risposta (DoR) è definita come il cambiamento relativo della somma dei diametri maggiori delle lesioni target RECIST al nadir, in assenza di comparsa di nuove lesioni o progressione delle lesioni non-target, rispetto al basale.; Tasso di resezioni secondarie R0.
Il tasso di resezioni R0 è definito come la percentuale di pazienti, relativa al totale dei soggetti arruolati, che sono sottoposti a resezione secondaria delle metastasi R0. La resezione chirurgica R0 è definita come resezione di tutto il residuo di malattia con margini chirurgici microscopicamente liberi da malattia, effettuata durante il trattamento o dopo il suo completamento, permesso dalla riduzione della massa tumorale o dalla scomparsa di una o più lesioni.; Analisi traslazionali.

E.5.2.1

Timepoint(s) of evaluation of this end point

48 months; 48 months; 48 months; 48 months; 48 months; 48 months; 48 months; 48 months

48 mesi; 48 mesi; 48 mesi; 48 mesi; 48 mesi; 48 mesi; 48 mesi; 48 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

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)

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

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

nel braccio sperimentale un chemioterapico in più(Irinotecano)

Experimental Arm additional of third chemotherapy agent (Irinotecan)

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

June 2021

Giugno 2021

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:

300

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

132

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

432

F.4.2

For a multinational trial

F.4.2.1

In the EEA

432

F.4.2.2

In the whole clinical trial

432

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)

SAE will be monitored up to 30 days from last dose. other treatment after progression will be at investigator's choice.

follow up safety fino a 30 giorni ultima dose. dopo la progressione il trattamento eventuale è a discrezione dello sperimentatore.

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

2017-06-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-06-22

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-06-24

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