Efficacy and Safety of Simtuzumab (SIM) With FOLFIRI as Second Line Treatment in Colorectal Adenocarcinoma
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms; Adenocarcinoma
Intervention: Simtuzumab; Placebo to match SIM; Leucovorin; Irinotecan; Fluorouracil
Intervention description: SIM administered via intravenous infusion over 30 minutes; Placebo to match SIM administered via intravenous infusion over 30 minutes; l-Leucovorin 200 mg/m^2 or dl-leucovorin 400 mg/m^2 administered via intravenous infusion over 2 hours; Irinotecan 180 mg/m^2 administered via intravenous infusion over 90 minutes; Fluorouracil 400 mg/m^2 administered via intravenous bolus and 2400 mg/m^2 via intravenous infusion over 46 hours
Intervention MeSH terms: Leucovorin; Fluorouracil; Irinotecan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 266.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: GSI; Gilead; Gilead Sciences; GS-6624; Colorectal Cancer; KRAS; Oncology; monoclonal antibody

Summary:

      The primary objective of this study is to compare the additive efficacy of SIM versus placebo
      in combination with leucovorin (folinic acid), irinotecan, and fluorouracil (FOLFIRI) as
      measured by improvement in progression-free survival (PFS) in participants with metastatic
      KRAS mutant colorectal adenocarcinoma who have progressed following a first-line oxaliplatin-
      and fluoropyrimidine-containing regimen.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Metastatic colorectal carcinoma with KRAS mutation

          -  Received first line therapy and discontinued part or all of first line therapy

          -  Estimated life expectancy > 3 months

          -  Stage IV disease

          -  Eastern Cooperative Oncology Group (ECOG) performance status: 0-2

          -  Adequate hepatic and hematologic function

          -  No major operations within 4 weeks prior to treatment start

        Exclusion Criteria:

          -  More than 1 prior chemotherapy regimen for Stage 4 colorectal cancer

          -  Experimental medical treatment within 30 days prior to study entry

          -  Known or suspected cerebral metastases

          -  History or presence of any form of cancer, other that colorectal cancer, within the 3
             years prior to enrollment

          -  Known dihydropyrimidine dehydrogenase-deficiency (special screening not required)

          -  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 electrocardiogram
             (ECG) abnormalities consistent with ischemia

          -  Uncontrolled hypertension (seated systolic blood pressure > 180 mm Hg or diastolic
             blood pressure > 110 mm Hg) at screening

          -  Clinically active liver disease, including active hepatitis (any etiology) or
             cirrhosis

          -  Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy,
             retinoid therapy, hormonal therapy) within 21 days prior to randomization

          -  Prior irinotecan therapy for metastatic disease is not permitted

          -  Systemic fungal, bacterial, viral, or other infection

        Note: Other protocol defined Inclusion/Exclusion criteria may apply.