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.
- Conditions
- Metastatic KRAS Mutant Colorectal AdenocarcinomaMedDRA version: 17.1Level: PTClassification code 10052360Term: Colorectal adenocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2011-003754-61-PL
- Lead Sponsor
- Gilead Sciences, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 266
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:
o Experienced radiographic disease progression during
first-line therapy, or
o Experienced radiographic disease progression within
6 months after the last dose of first-line therapy, or
o 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
o 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 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.
9. 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.
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:
o neutrophils = 1.5 x 109/L
o platelets = 100 x 109/L
o 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 CstableCTT 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:
o Direct or total bilirubin = 1.5 x upper limit of normal
(ULN).
o ALT and AST = 2.5 x ULN, in case of liver
metastases = 5 x ULN.
14. Serum creatinine = 1.5 x 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
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 antibiotics 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method