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.

• Register: EUCTR
• Last refreshed on: 26 January 2015
• Main ID: EUCTR2011-003754-61-DE
• Date of registration: 16/04/2012
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences, Inc.
• Public title: 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.
• Scientific title: 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.
• Date of first enrolment: 12/07/2012
• Target sample size: 266
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-003754-61
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

France, Germany, Italy, Poland, Spain, United States

Contacts

• Name: Medical Monitor
• Affiliation: Gilead Sciences, Inc.

• Name: Medical Monitor
• Affiliation: Gilead Sciences, Inc.

Key inclusion & exclusion criteria

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.

Are the trial subjects under 18? no
Number of subjects for this age range:
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 10

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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Metastatic KRAS Mutant Colorectal Adenocarcinoma
MedDRA version: 17.0 Level: PT Classification code 10052360 Term: Colorectal adenocarcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Code: GS-6624
Pharmaceutical Form: Solution for infusion
Current Sponsor code: GS-6624
Other descriptive name: GS-6624
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Secondary Objective: • 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.

Primary end point(s): Progression free survival signs

Main Objective: 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.

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.

Secondary Outcome(s)

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.

Timepoint(s) of evaluation of this end point: Overall survival is measured as time from date of randomization to death regardless of cause.

Secondary ID(s)

GS-US-295-0203

2011-003754-61-ES

Source(s) of Monetary Support

Gilead Sciences, Inc.