Clinical Trials Register

Summary
EudraCT Number:	2011-003754-61
Sponsor's Protocol Code Number:	GS-US-295-0203
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2012-04-12
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

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.

Estudio de fase 2, aleatorizado, doble ciego, controlado con placebo para evaluar la eficacia y seguridad del GS-6624 combinado con FOLFIRI como tratamiento de segunda línea para el adenocarcinoma colorrectal metastásico con mutaciones en KRAS que ha experimentado progresión después de un tratamiento de primera línea con oxaliplatino y 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. We want to find out what effects, good and/or bad, GS-6624 has on you and your metastatic colorectal adenocarcinoma when it is given with FOLFIRI.

Ensayo clínico para investigar un producto experimental llamado GS-6624 para el tratamiento del adenocarcinoma colorrectal metastásico, un sub-tipo de cancer de colon y/o recto.

El propósito del estudio es evaluar la efectividad y la seguridad de GS-6624 a diferentes dosis cuando se administra junto con FOLFIRI. Se pretende averiguar qué efectos, buenos y/o malos produce GS-6624 sobre usted y sobre su adenocarcinoma colorrectal metastásico cuando se administra 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 Sciences, 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	+1650522 4707
B.5.5	Fax number	+1866454 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.3.2	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.3.9.2	Current sponsor code	GS-6624
D.3.9.3	Other descriptive name	GS-6624
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	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.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 colorrectal con mutación en KRAS

E.1.1.1

Medical condition in easily understood language

Metastatic Mutant Colorectal Cancer

Cáncer colorrectal metastásico mutante.

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	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) in subjects with metastatic KRAS mutant colorectal adenocarcinoma who have progressed
following a first line oxaliplatin- and fluoropyrimidine-containing regimen.

Comparar la eficacia acumulada del GS-6624 respecto al placebo en combinación con FOLFIRI medida por la mejora de la supervivencia libre de progresión (SLP) en los sujetos con adenocarcinoma colorrectal metastásico con mutaciones en KRAS que hayan experimentado progresión de la enfermedad después de un tratamiento de primera línea con oxaliplatino y fluoropirimidina.

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.

? Comparar la eficacia acumulada del GS-6624 respecto al placebo en combinación con FOLFIRI medida según la mejora en la supervivencia general;
? Comparar la eficacia acumulada del GS-6624 respecto al placebo en combinación con FOLFIRI medida según la mejora en la tasa de respuesta objetiva según los criterios RECIST (versión 1.1);
? Comparar la seguridad del GS-6624 respecto al placebo en combinación con FOLFIRI medida por la incidencia de acontecimientos adversos, reacciones en el lugar de la inyección y las alteraciones clínicas relevantes en los valores de laboratorio, el ECG y las constantes vitales.

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 o 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, defined with all of following criteria: 1. Lesions accurately measured in at least 1 dimension 2. The longest diameter in the plane of measurement is to be recorded 3. A minimum size of 10 mm if CT slice thickness ? 5 mm; if thickness is > 5 mm then the minimum size of measurable lesions should be twice slice thickness.
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.
15. No relevant toxicities due to prior medical treatment at time
of study entry.

1. Adenocarcinoma del colon o el recto con mutaciones en KRAS confirmado histológicamente.
2. El sujeto debe haber recibido tratamiento combinado de primera línea con oxaliplatino y una fluoropirimidina con o sin bevacizumab para enfermedad metastásica y
?Haber experimentado progresión radiográfica de la enfermedad durante el tratamiento de primera línea, o
?Haber experimentado progresión radiográfica de la enfermedad en los seis meses posteriores a la última dosis del tratamiento de primera línea, o
?Haber interrumpido parte o la totalidad del tratamiento de primera línea debido a toxicidad y haber experimentado progresión radiográfica de la enfermedad en los seis meses posteriores a la última dosis del tratamiento de primera línea; o
?Haber experimentado progresión radiográfica de la enfermedad tras la terapia de primera línea y no ser apto para un tratamiento con oxaliplatino adicional.
3. Enfermedad en estadio IV.
4. ECOG 0-2.
5. Mayor de 18 años.
6. Esperanza de vida estimada > 3 meses.
7. Enfermedad medible con los criterios RECIST (versión 1.1), definida con todos los siguientes criterios:
1.Lesiones medidas con exactitud en al menos una dimensión
2.Debe registrarse el mayor diámetro en el plano de la medición
3.Tamaño mínimo de 10 mm si el grosor de corte de la TC es menos o igual a 5 mm; si el grosor es > 5 mm, el tamaño mínimo de las lesiones medibles debe ser el doble del grosor del corte.
8. Las mujeres fértiles deben acceder a utilizar un método anticonceptivo médicamente aprobado (esto es, mecánico o farmacológico) y sus parejas deben acceder a usar un método anticonceptivo de barrera adicional durante la totalidad del estudio y hasta 90 días después de la última administración del fármaco del estudio.
9. Los sujetos de sexo masculino deben acceder a utilizar preservativos durante las relaciones sexuales y a no donar esperma durante la totalidad del estudio y hasta 90 días después de la última administración del fármaco del estudio.
10. Función hematológica adecuada:
?neutrófilos mayor o igual a 1,5 x 109/l
?trombocitos mayor o igual a 100 x 109/l
?hemoglobina mayor o igual a 9 g/dl.
11. Coagulación: Índice internacional normalizado (International Normalized Ratio, INR) menor o igual a 1,6 (a menos que se reciba tratamiento anticoagulante). Los pacientes con anticoagulación a dosis completa deben recibir una dosis estable (duración mínima de 14 días) de anticoagulante oral o heparina de bajo peso molecular. Si está recibiendo warfarina, el paciente debe tener un INR menor o igual a 3,0 y ninguna hemorragia activa (esto es, ninguna hemorragia en los 14 días previos a la primera dosis del tratamiento del estudio).
12. Función hepática adecuada:
?Bilirrubina directa o total menor o igual a 1,5 x límite superior de lo normal (LSN).
?ALT y AST menor o igual a 2,5 x LSN, en caso de metástasis hepáticas menor o igual a 5 x LSN.
13. Creatinina sérica menor o igual a 1,5 x LSN.
14. Ninguna operación de cirugía mayor en las cuatro semanas previas al inicio del tratamiento.
15. Ninguna toxicidad relevante del tratamiento médico previo en el momento de la entrada en el estudio.

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, formulation excipients, irinotecan, 5 FU,
or leucovorin.

1. Más de un tratamiento quimioterapéutico previo para el cáncer colorrectal en estadio 4.
2. Tratamiento médico experimental en los 30 días previos a la entrada en el estudio.
3. Mujeres embarazadas o lactantes (el embarazo debe descartarse mediante pruebas de detección de beta HCG).
4. Metástasis cerebrales presuntas o conocidas.
5. Íleo agudo o subagudo, enfermedad intestinal inflamatoria crónica o diarrea crónica.
6. Deficiencia conocida de dihidropirimidina deshidrogenasa (no es necesario un cribado especial).
7. Deficiencia conocida de la glucuronoconjugación (no es necesario un cribado especial).
8. Abuso conocido de alcohol o drogas u otro trastorno médico o psiquiátrico que contraindique la participación en el estudio.
9. Antecedentes o presencia de cualquier tipo de cáncer, distinto de cáncer colorrectal, en los tres años previos a la inclusión, con la excepción de carcinoma basocelular o espinocelular de la piel extirpado o carcinoma cervicouterino in situ o carcinoma de mama in situ que ha sido extirpado o resecado por completo y del que no hay signos de recidiva local o metástasis
10. Infarto de miocardio en los seis meses previos al día 1 del estudio, insuficiencia cardíaca congestiva sintomática (clasificación de la Asociación Cardiológica de Nueva York > clase II), angina de pecho inestable o arritmia cardíaca inestable que requiere tratamiento farmacológico;
11. Enfermedad hepática clínicamente activa, incluyendo hepatitis activa (de cualquier etiología) o cirrosis.
12. Infección sistémica fúngica, bacteriana, vírica u otra que no esté controlada (se define como que muestra signos/síntomas continuos relacionados con la infección y no mejora) a pesar del uso de los antibióticos apropiados.
13. Tratamiento antitumoral (quimioterapia, tratamiento con anticuerpos, tratamiento molecular dirigido, tratamiento retinoide, tratamiento hormonal) en los 21 días previos a la aleatorización;
14. No se permite el tratamiento previo con irinotecán para la enfermedad metastásica. Sin embargo, se permite la terapia adyuvante previa con irinotecán.
15. Hipersensibilidad conocida a los productos en investigación del estudio, los excipientes de la formulación, el irinotecán, el 5-FU o la leucovorina.

E.5 End points

E.5.1

Primary end point(s)

Progression free survival signs

Signos de supervivencia libre de progresión.

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.

Supervivencia libre de progresión. Se evalúa como el tiempo transcurrido desde la fecha de aleatorización hasta el primer evento de a) muerte sin importar la causa o b) primer indicador de progresión de la enfermedad.

E.5.2

Secondary end point(s)

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 supervivencia total se mide por el tiempo transcurrido desde la fecha de aleatorización hasta la muerte, por la causa que sea.

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

France

Germany

Italy

Poland

Spain

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

Last patient, last visit

Última visita del último paciente.

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:

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.

Los sujetos recibirán el nivel de cuidados habituales previsto por los centros en que son tratados tras terminar su participación en el ensayo.

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

2012-05-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-03-09

P. End of Trial
P.	End of Trial Status	Prematurely Ended

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials