Clinical Trials Register

Summary
EudraCT Number:	2011-003754-61
Sponsor's Protocol Code Number:	GS-US-295-0203
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2012-04-16
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

Germany - PEI

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.

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.

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 1288
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

E.1.1.1

Medical condition in easily understood language

Metastatic Mutant Colorectal Cancer

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	17.0
E.1.2	Level	PT
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.

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.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subject has signed the written informed consent
2. KRAS mutated, histologically confirmed adenocarcinoma of the colon or rectum that is not amenable to complete surgical resection.
3. The subject must have received first-line combination therapy containing oxaliplatin, and a fluoropyrimidine with or without bevacizumab for metastatic disease and must not be a candidate for further oxaliplatin, meeting one of the following criteria:
• 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
• Experienced radiographic disease progression following first line therapy and not
be a candidate for therapy with additional oxaliplatin.
4. Stage IV disease.
5. ECOG 0-2.
6. Age ≥ 18 years.
7. Estimated life expectancy > 3 months.
8. Measurable disease per RECIST (ver. 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.
9. Women of childbearing potential must agree to use one medically approved (i.e., 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.
10. Male subjects must agree to use protocol-recommended methods of contraception during heterosexual intercourse and avoid sperm donation for the duration of this study and for 90 days after the last administration of study drug.11. Adequate hematologic function:
• neutrophils ≥ 1.5 x 109/L
• platelets ≥ 100 x 109/L
• hemoglobin ≥ 9 g/dL.
12. Coagulation: International Normalized Ratio (INR) ≤ 1.6 (unless receiving anticoagulation therapy). Patients on full-dose 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).
13. Adequate hepatic function:
• Direct or total bilirubin ≤ 1.5 x upper limit of normal (ULN).
• ALT and AST ≤ 2.5x ULN, in case of liver metastases ≤ 5x ULN.
14. Serum creatinine ≤ 1.5x ULN OR creatinine clearance ≥ 60 ml/minute as calculated by the Cockroft-Gault method.
15. No major operations within 4 weeks prior to treatment start.
16. No relevant toxicities due to prior medical treatment at time of study entry.

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 homozygosity for the UGT1A1*28 allele (UGT1A1 7/7 genotype) (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, stage 0 or 1 melanoma, 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. Subjects with angina pectoris, poorly controlled ventricular arrhythmias (does not include asymptomatic, occasional premature ventricular contractions), history of clinically significant coronary heart disease or cardiomyopathy, or ECG abnormalities consistent with ischemia.11. Uncontrolled hypertension (seated systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg) at Screening.
12. Clinically active liver disease, including active hepatitis (any etiology) or cirrhosis.
13. 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 antibiotic use.
14. Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, retinoid therapy, hormonal therapy) within 21 days prior to randomization;
15. Prior irinotecan therapy for metastatic disease is not permitted. However, prior adjuvant therapy with irinotecan is permitted. The use of prior fluoropyrimidine and/or oxaliplatin as adjuvant therapy is permitted but the subject must also have received fluoropyrimidine and oxaliplatin as first line therapy for metastatic disease.
16. Known hypersensitivity to the study investigational medicinal products, formulation
excipients, irinotecan, 5 FU or leucovorin

E.5 End points

E.5.1

Primary end point(s)

Progression free survival signs

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.

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.

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

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:

256

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

266

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 our trials (both) subjects will receive appropriate standard of care provided at the respective institutions.

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

2012-05-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-07-12

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

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