Clinical Trials Register

Summary
EudraCT Number:	2011-003754-61
Sponsor's Protocol Code Number:	GS-US-295-0203
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2012-03-06
Trial results	View 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

2011-003754-61

A.3

Full title of the trial

A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of GS-6624 Combined with FOLFIRI as Second Line Treatment for Metastatic KRAS Mutant Colorectal Adenocarcinoma that Has Progressed Following a First Line Oxaliplatin- and Fluoropyrimidine-Containing Regimen.

Studio di fase 2 randomizzato, doppio cieco, controllato con placebo per valutare l'efficacia e la sicurezza di GS-6624 combinato con FOLFIRI come trattamento di seconda linea per l'adenocarcinoma colo-rettale metastatico, mutante KRAS con progressione dopo un regime di prima linea con oxaliplatino e fluoropirimidina.

A.3.1

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

This is a clinical research study involving an experimental drug named GS-6624 for the treatment of metastatic colorectal adenocarcinoma, a sub-type of cancer of the colon and/or rectum. The purpose of this study is to test the effectiveness and safety of GS-6624 at different dose levels when it is given with FOLFIRI.

Studio clinico con un medicinale sperimentale chiamato GS-6624 per il trattamento dell'adenocarcinoma colo-rettale metastatico, un sottotipo di cancro del colon e/o del retto. Lo scopo di questo studio e' di valutare l'efficacia e la sicurezza di GS-6624 a diversi dosaggi quando somministrato con FOLFIRI.

A.4.1

Sponsor's protocol code number

GS-US-295-0203

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	GILEAD SCIENCE INC.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Gilead Sciences Inc.
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	Gilead Sciences Inc.
B.5.2	Functional name of contact point	Medical Monitor
B.5.3	Address:
B.5.3.1	Street Address	333 Lakeside Drive
B.5.3.2	Town/ city	Foster City
B.5.3.3	Post code	CA 94404
B.5.3.4	Country	United States
B.5.4	Telephone number	+1 650 522 4707
B.5.5	Fax number	+1 866 454 1397
B.5.6	E-mail	zung.thai@gilead.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	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	NA
D.3.2	Product code	GS-6624
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	NA
D.3.9.1	CAS number	NA
D.3.9.2	Current sponsor code	GS-6624
D.3.9.3	Other descriptive name	NA
D.3.9.4	EV Substance Code	NA
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	10
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	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	Yes
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for injection
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	FLUOROURACIL
D.3.9.1	CAS number	51-21-8
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	NA
D.3.9.4	EV Substance Code	SUB07721MIG
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	non noto
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.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	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	IRINOTECAN HYDROCHLORIDE
D.3.9.1	CAS number	136572-09-3
D.3.9.4	EV Substance Code	SUB02772MIG
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	non noto
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.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CALCIUM LEVOFOLINATE PENTAHYDRATE
D.3.9.4	EV Substance Code	SUB11775MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	up to
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	non noto

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Metastatic KRAS Mutant Colorectal Adenocarcinoma

Adenocarcinoma colo-rettale metastatico KRAS mutante

E.1.1.1

Medical condition in easily understood language

Metastatic Mutant Colorectal Cancer

Tumore metastatico mutante del colonretto

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	SOC
E.1.2	Classification code	10029104
E.1.2	Term	Neoplasms benign, malignant and unspecified (incl cysts and polyps)
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10052360
E.1.2	Term	Colorectal adenocarcinoma
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 the additive efficacy of GS-6624 vs. placebo in combination with FOLFIRI as measured by improvement in progression free survival (PFS).

Confrontare l'efficacia additiva di GS-6624 rispetto al placebo in combinazione con FOLFIRI, misurata in base al miglioramento della sopravvivenza senza progressione (PFS, progression-free survival).

E.2.2

Secondary objectives of the trial

• To compare the additive efficacy of GS-6624 vs. placebo in combination with FOLFIRI as measured by improvement in overall survival; • To compare the additive efficacy of GS-6624 vs. placebo in combination with FOLFIRI as measured by improvement in objective response rate per RECIST (ver. 1.1); • To compare the safety of GS-6624 vs. placebo in combination with FOLFIRI as measured by incidence of adverse events, infusion site reactions, clinical relevant changes in laboratory values, ECG, and vital signs

Confrontare l'efficacia additiva di GS-6624 rispetto al placebo in combinazione con FOLFIRI, misurata in base: - al miglioramento della sopravvivenza globale; - al tasso di risposta obiettiva con RECIST[Response Evaluation Criteria in Solid Tumors]( ver.1.1). Confrontare la sicurezza di GS-6624 vs placebo in combinazione con FOLFIRI come misurazione dell'incidenza di eventi avversi, reazioni presso il sito di infusione, cambiamenti clinicamente rilevanti nei valori di laboratorio, ECG e parametri vitali.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. KRAS mutated, histologically confirmed adenocarcinoma of the colon or rectum. 2. The subject must have received first-line combination therapy containing oxaliplatin and a fluoropyrimidine with or without bevacizumab for metastatic disease and or Experienced radiographic disease progression during first-line therapy, or Experienced radiographic disease progression within 6 months after the last dose of first-line therapy, or Discontinued part or all of first-line therapy due to toxicity and experienced radiographic disease progression within 6 months after the last dose of first-line therapy; or Not be a candidate for therapy with additional oxaliplatin. 3. Stage IV disease. 4. ECOG 0-2. 5. Age ≥ 18 years. 6. Estimated life expectancy > 3 months. 7. Measurable disease per RECIST version 1.1. 8. Women of childbearing potential must agree to use one medically approved (ie, mechanical or pharmacological) contraceptive measure and have their partners agree to an additional barrier method of contraception for the duration of the study and for 90 days after the last administration of study drug. 9. Male subjects must agree to use condoms during heterosexual intercourse and avoid sperm donation for the duration of this study and for 90 days after the last administration of study drug. 10. Adequate hematologic function: neutrophils ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, hemoglobin ≥ 9 g/dL. 11. Coagulation: International Normalized Ratio (INR) ≤ 1.6 (unless receiving anticoagulation therapy). Patients on fulldose anticoagulation must be on a stable dose (minimum duration 14 days) of oral anticoagulant or low molecular weight heparin. If receiving warfarin, the patient must have an INR ≤ 3.0 and no active bleeding (ie, no bleeding within 14 days prior to first dose of study therapy). 12. Adequate hepatic function: Direct or total bilirubin ≤ 1.5 x upper limit of normal (ULN). ALT and AST ≤ 2.5 x ULN, in case of liver metastases ≤ 5 x ULN. 13. Serum creatinine ≤ 1.5 x ULN. 14. No major operations within 4 weeks prior to treatment start.

1. Adenocarcinoma mutato KRAS, confermato dall’esame istologico del colon o del retto. 2. Il soggetto deve avere ricevuto una terapia combinatoria di prima linea contenente oxaliplatino e una fluoropirimidina con o senza bevacizumab per malattia metastatica e : - aver riscontrato progressione radiografica della malattia confermata durante la terapia di prima linea, - aver riscontrato progressione radiografica della malattia confermata entro 6 mesi dall’ultima dose di terapia di prima linea, o - aver interrotto parte della terapia o tutta la terapia di prima linea a causa della tossicità e progressione radiografica della malattia confermata entro 6 mesi dall’ultima dose di terapia di prima linea, o - aver riscontrato progressione radiografica della malattia confermata dopo terapia di prima linea e non essere candidato alla terapia con oxaliplatino aggiuntivo. 3. Malattia di Stadio IV. 4. ECOG 0-2. 5. Età ≥ 18 anni. 6. Aspettativa di vita stimata > 3 mesi. 7. Malattia misurabile in base a RECIST versione 1.1. 8. Le donne potenzialmente fertili devono convenire di utilizzare una misura contraccettiva approvata dal medico (cioè, meccanica o farmacologica) e fare accettare al partner di utilizzare un ulteriore metodo barriera di contraccezione per la durata dello studio e per 90 giorni dopo l’ultima somministrazione del farmaco in studio. 9. I soggetti di sesso maschile devono convenire di utilizzare il preservativo durante il rapporto eterosessuale e di evitare la donazione dello sperma per la durata dello studio e per i 90 giorni dopo l’ultima somministrazione del farmaco in studio. 10. Funzionalità ematologica adeguata: - neutrofili ≥ 1,5 x 109/l; - piastrine ≥ 100 x 109/l; - emoglobina ≥ 9 g/dl. 11. Coagulazione: rapporto normalizzato internazionale (INR, International Normalized Ratio) ≤ 1,6 (a meno che non riceva terapia anticoagulante). I pazienti con dose completa di anticoagulante devono assumere una dose stabile (durata minima 14 giorni) di anticoagulante orale o di eparina a basso peso molecolare. Se assume warfarin, il paziente deve avere un INR ≤ 3.0 e senza emorragia attiva (cioè, senza emorragia nei 14 giorni prima della prima dose della terapia dello studio). 12. Funzionalità epatica adeguata: - bilirubina diretta o totale ≤ 1,5 x limite superiore della norma (ULN); - ALT e AST ≤ 2,5 x ULN, in caso di metastasi al fegato ≤ 5 x ULN. 13. Creatinina sierica ≤ 1,5 x ULN. 14. Nessuna operazione importante nelle 4 settimane precedenti l’inizio del trattamento.

E.4

Principal exclusion criteria

1. More than 1 prior chemotherapy regimen for stage 4 colorectal cancer. 2. Experimental medical treatment within 30 days prior to study entry. 3. Pregnant or breast feeding women (pregnancy needs to be excluded by testing of beta-HCG). 4. Known or suspected cerebral metastases. 5. Acute or subacute ileus, chronic inflammatory bowel disease, or chronic diarrhea. 6. Known dihydropyrimidine dehydrogenase-deficiency (special screening not required). 7. Known glucuronidation-deficiency (special screening not required). 8. Known alcohol or drug abuse or any other medical or psychiatric condition which contraindicates participation in the study. 9. History or presence of any form of cancer, other than colorectal cancer, within the 3 years prior to enrollment, with the exception of excised basal cell or squamous cell carcinoma of the skin, or cervical carcinoma in situ or breast carcinoma in situ that has been excised or resected completely and is without evidence of local recurrence or metastasis. 10. Myocardial infarction within the last 6 months of study Day 1, symptomatic congestive heart failure (New York Heart Association Classification > Class II), unstable angina, or unstable cardiac arrhythmia requiring medication. 11. Clinically active liver disease, including active hepatitis (any etiology) or cirrhosis. 12. Systemic fungal, bacterial, viral, or other infection that is not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement) despite appropriate antibiotics use. 13. Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, retinoid therapy, hormonal therapy) within 21 days prior to randomization. 14. Prior irinotecan therapy. 15. Known hypersensitivity to the study investigational medicinal products.

1. Più di un regime chemioterapico precedente per il cancro colo-rettale stadio 4. 2. Trattamento medico sperimentale nei 30 giorni precedenti l’ingresso nello studio. 3. Donne incinte o in allattamento (la gravidanza deve essere esclusa tramite analisi del beta-HCG). 4. Metastasi cerebrali note o sospette. 5. Ileo acuto o sub-acuto, malattia intestinale infiammatoria cronica, o diarrea cronica. 6. Carenza nota di diidropirimidina deidrogenasi (non è necessario uno screening speciale). 7. Carenza di glucuronidazione nota (non è necessario uno screening speciale). 8. Abuso di alcol o droghe noto o altre malattie o disturbi psichiatrici che sono una controindicazione per la partecipazione allo studio. 9. Anamnesi o presenza di qualunque forma di cancro, diverso dal cancro colo-rettale, nei 3 anni precedenti all’arruolamento, con l’eccezione del carcinoma a cellule squamose o a cellule basali escisso o del carcinoma cervicale in situ o del carcinoma alla mammella in situ che è stato escisso o resecato completamente ed è senza evidenza di recidiva locale o metastasi. 10. Infarto miocardico negli ultimi 6 mesi dello studio del Giorno 1, insufficienza cardiaca congestizia sintomatica (New York Heart Association Classification > Classe II), angina instabile, o aritmia cardiaca instabile che richiede l’intervento farmacologico. 11. Malattia epatica clinicamente attiva, compresa l’epatite attiva (qualunque eziologia) o la cirrosi. 12. Infezioni sistemiche fungine, batteriche, virali o di altro tipo non controllate (definite come con segni/sintomi in corso correlati all’infezione e senza miglioramento) nonostante l’uso di antibiotici adeguati. 13. Terapia antitumorale (chemioterapia, terapia anticorpale, terapia molecolare mirata, terapia retinoide, terapia ormonale) nei 21 giorni precedenti la randomizzazione. 14. Non è ammessa una precedente terapia con irinotecan per lesioni metastatiche. Tuttavia, è permessa una precedente terapia adiuvante con irinotecan. 15. Ipersensibilità nota ai prodotti medicinali sperimentali dello studio.

E.5 End points

E.5.1

Primary end point(s)

Progression free survival signs

Miglioramento nella sopravvivenza senza progressione

E.5.1.1

Timepoint(s) of evaluation of this end point

Progression free survival is the primary endpoint of the study and is measured as time from date of randomization to the earliest event time of a) death regardless of cause, or b) first indication of disease progression.

La sopravvivenza senza progressione è l'end point primario dello studio ed è misurato come tempo dalla data di randomizzazione al primo evento di a) decesso indipendente dalla causa o b) primo segnale di progressione della malattia.

E.5.2

Secondary end point(s)

• To compare the additive efficacy of GS-6624 vs. placebo in combination with FOLFIRI as measured by improvement in overall survival; • To compare the additive efficacy of GS-6624 vs. placebo in combination with FOLFIRI as measured by improvement in objective response rate per RECIST (ver. 1.1); • To compare the safety of GS-6624 vs placebo in combination with FOLFIRI as measured by incidence of adverse events, infusion site reactions, clinical relevant changes in laboratory values, ECG, and vital signs.

Confrontare l'efficacia additiva di GS-6624 rispetto al placebo in combinazione con FOLFIRI misurata in base: - alla sopravvivenza globale (OS, Overall Survival); - al tasso di risposta obiettiva (con RECIST [Response Evaluation Criteria in Solid Tumors]). Confrontare la sicurezza di GS-6624 vs placebo in combinazione con FOLFIRI come incidenza di eventi avversi, reazioni presso il sito di infusione, cambiamenti clinicamente rilevanti nei valori di laboratorio, ECG e parametri vitali.

E.5.2.1

Timepoint(s) of evaluation of this end point

Overall survival is measured as time from date of randomization to death regardless of cause.

La sopravvivenza globale è misurata come tempo dalla data di randomizzazione al decesso indipendente dalla causa.

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

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Yes

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

United States

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

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

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

255

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

173

F.4.2.2

In the whole clinical trial

265

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)

After termination from the trial subjects will receive appropriate standard of care provided at the respective institutions.

Al termine dello studio i soggetti riceveranno le cure standard appropriate presso le rispettive Strutture.

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

2012-03-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-02-17

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2015-01-22

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Orphan Designation Number:
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