Efficacy and Safety of Simtuzumab (SIM) With FOLFIRI as Second Line Treatment in Colorectal Adenocarcinoma

Gilead Sciences

Status and phase: Terminated; Phase 2

Conditions: Colorectal Cancer

Treatments: Drug: Fluorouracil; Drug: Irinotecan; Biological: Simtuzumab; Drug: Placebo to match SIM; Drug: Leucovorin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01479465

GS-US-295-0203

2011-003754-61 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 266 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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266 participants in 4 patient groups

FOLFIRI + SIM 700 mg (Part A)

Experimental group

Description:

Participants will receive SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycle until disease progression or unacceptable toxicity.

Treatment:

Drug: Irinotecan

Biological: Simtuzumab

Drug: Fluorouracil

Drug: Leucovorin

FOLFIRI + SIM 200 mg (Part B)

Experimental group

Description:

Participants will receive SIM 200 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycle until disease progression or unacceptable toxicity.

Treatment:

Drug: Irinotecan

Biological: Simtuzumab

Drug: Fluorouracil

Drug: Leucovorin

FOLFIRI + SIM 700 mg (Part B)

Experimental group

Description:

Participants will receive SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycle until disease progression or unacceptable toxicity.

Treatment:

Drug: Irinotecan

Biological: Simtuzumab

Drug: Fluorouracil

Drug: Leucovorin

FOLFIRI + Placebo (Part B)

Experimental group

Description:

Participants will receive placebo to match SIM via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycle until disease progression or unacceptable toxicity.

Treatment:

Drug: Irinotecan

Drug: Placebo to match SIM

Drug: Fluorouracil

Drug: Leucovorin