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

Phase 2

Terminated

• Conditions: Colorectal Cancer
• Interventions: Drug: Placebo to match SIM; Biological: Simtuzumab; Drug: Leucovorin; Drug: Irinotecan; Drug: Fluorouracil

• Registration Number: NCT01479465
• Lead Sponsor: Gilead Sciences

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-11-09
• Study First Submitted QC: 2011-11-22
• Study First Posted: 2011-11-24
• Study Start: 2011-12
• Primary Completion: 2014-10
• Study Completion: 2015-02
• Disposition First Submitted: 2015-03-10
• Disposition First Submitted QC: 2015-03-10
• Disposition First Posted: 2015-03-30
• Status Verified: 2019-03
• Results First Submitted: 2019-03-26
• Results First Submitted QC: 2019-03-26
• Last Update Submitted: 2019-03-26
• Results First Posted: 2019-04-17
• Last Update Posted: 2019-04-17

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 266

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FOLFIRI + Placebo (Part B)	Placebo to match SIM	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.
FOLFIRI + SIM 700 mg (Part A)	Simtuzumab	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.
FOLFIRI + SIM 200 mg (Part B)	Simtuzumab	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.
FOLFIRI + SIM 700 mg (Part B)	Simtuzumab	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.
FOLFIRI + SIM 700 mg (Part A)	Leucovorin	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.
FOLFIRI + SIM 700 mg (Part A)	Irinotecan	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.
FOLFIRI + SIM 700 mg (Part A)	Fluorouracil	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.
FOLFIRI + SIM 200 mg (Part B)	Leucovorin	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.
FOLFIRI + Placebo (Part B)	Irinotecan	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.
FOLFIRI + SIM 200 mg (Part B)	Irinotecan	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.
FOLFIRI + SIM 200 mg (Part B)	Fluorouracil	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.
FOLFIRI + SIM 700 mg (Part B)	Irinotecan	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.
FOLFIRI + SIM 700 mg (Part B)	Leucovorin	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.
FOLFIRI + SIM 700 mg (Part B)	Fluorouracil	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.
FOLFIRI + Placebo (Part B)	Leucovorin	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.
FOLFIRI + Placebo (Part B)	Fluorouracil	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.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	Randomization up to 27 months	The PFS was defined as the time from the date of randomization to the earliest event time of: a) death regardless of cause, or b) first indication of disease progression. PFS was analyzed using Kaplan-Meier (KM) estimates.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Randomization up to 33 months	The OS is measured as time from date of randomization to death regardless of cause. The OS was analyzed using KM estimates.
Objective Response Rate (ORR)	Randomization up to 27 months	Objective response was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria (version 1.1) as Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD). The ORR was defined as the percentage of participants who achieved a CR or PR.

Trial Locations

Locations (103)

Clearview Cancer Institute; 🇺🇸 Huntsville, Alabama, United States

Banner MD Anderson Cancer Center; 🇺🇸 Gilbert, Arizona, United States

Central Hematology Oncology Medical Group, Inc.; 🇺🇸 Alhambra, California, United States

Comprehensive Blood and Cancer Center; 🇺🇸 Bakersfield, California, United States

Providence Saint Joseph Medical Center-Disney Family Cancer Center; 🇺🇸 Burbank, California, United States

Wilshire Oncology Medical Group, Inc.; 🇺🇸 Pomona, California, United States

Saint Jude Heritage Healthcare; 🇺🇸 Fullerton, California, United States

University of California San Diego Medical Center; 🇺🇸 La Jolla, California, United States

Pacific Shores Medical Group; 🇺🇸 Redondo Beach, California, United States

Comprehensive Hematology Oncology Centers, Inc.; 🇺🇸 Los Angeles, California, United States

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