Efficacy and Safety of Simtuzumab (SIM) With FOLFIRI as Second Line Treatment in Colorectal Adenocarcinoma
- Conditions
- Colorectal Cancer
- Interventions
- 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
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 266
- 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
- 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)
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Providence Saint Joseph Medical Center-Disney Family Cancer Center
🇺🇸Burbank, California, United States
Hematology and Oncology Associates at BridgePoint
🇺🇸Tupelo, Mississippi, United States
Southeast Nebraska Cancer Center
🇺🇸Lincoln, Nebraska, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Clearview Cancer Institute
🇺🇸Huntsville, Alabama, United States
Central Hematology Oncology Medical Group, Inc.
🇺🇸Alhambra, California, United States
Comprehensive Blood and Cancer Center
🇺🇸Bakersfield, 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
TORI Network (Translational Oncology Research Intl)
🇺🇸Los Angeles, California, United States
UCLA Community Oncology Practice
🇺🇸Los Angeles, California, United States
Stanford University Medical Center
🇺🇸Palo Alto, California, United States
Cancer Care Associates Medical Group
🇺🇸Redondo Beach, California, United States
San Jose Medical Group
🇺🇸San Jose, California, United States
Florida Cancer Specialists
🇺🇸Saint Petersburg, Florida, United States
Peachtree Hematology Oncology Consultants, PC
🇺🇸Atlanta, Georgia, United States
Suburban Hematology Oncology Associates, PC
🇺🇸Lawrenceville, Georgia, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Indiana University Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Saint Joseph Oncology, Inc.
🇺🇸Saint Joseph, Missouri, United States
Signal Point Clinical Research Center, LLC
🇺🇸Middletown, Ohio, United States
New York University Clinical Cancer Center
🇺🇸New York, New York, United States
Oncology Hematology Care, Inc.
🇺🇸Wilmington, Ohio, United States
South Carolina Oncology Associates
🇺🇸Columbia, South Carolina, United States
University of Texas Southwestern Medical Center at Dallas
🇺🇸Dallas, Texas, United States
Center for Cancer and Blood Disorders, PC
🇺🇸Fort Worth, Texas, United States
Joe Arrington Cancer Research and Treatment Center
🇺🇸Lubbock, Texas, United States
Scott & White Memorial
🇺🇸Temple, Texas, United States
The Center for Cancer and Blood Disorders
🇺🇸Weatherford, Texas, United States
Intermountain Healthcare
🇺🇸Saint George, Utah, United States
Virginal Cancer Specialists, PC
🇺🇸Fairfax, Virginia, United States
Virginia Cancer Institute
🇺🇸Richmond, Virginia, United States
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
Centre Hospitalier Universitaire Estaing
🇫🇷Clermont Ferrand, Auvergne, France
Centre Oscar Lambret, Dept. de Cancerologie Digestive et Urologique
🇫🇷Lille Cedex, France
Centre Eugène Marquis
🇫🇷Rennes Cedex, Bretagne, France
Centre Georges François Leclerc
🇫🇷Dijon, France
Centre Antoine Lacassagne
🇫🇷Nice Cedex 2, France
Centre Hospitalier Régional Universitaire Hôpital Saint Eloi
🇫🇷Montpellier Cedex 5, France
Institut Paoli Calmettes Centre Régional de Lutte Contre le Cancer
🇫🇷Rennes Cedex, France
Hôpital Trousseau - Service de Gastroenterologie
🇫🇷Tours, France
Universitätsklinikum Ulm
🇩🇪Ulm, Baden-Wuerttemberg, Germany
Universitätsklinikums Mannheim
🇩🇪Mannheim, Baden-Wuerttenberg, Germany
Ludwig-Maximilians-Universität München Klinikum Großhadern
🇩🇪München, Bayern, Germany
Universitätsklinikum Rostock
🇩🇪Rostock, Mecklenburg-Vorpommern, Germany
Klinikum Region Hannover GmbH, Krankenhaus Siloah
🇩🇪Hannover, Niedersachsen, Germany
Medizinische Universitätsklinik Bochum
🇩🇪Bochum, Nordrhein-Westfalen, Germany
Universitätsklinikum Essen
🇩🇪Essen, Nordrhein-Westfalen, Germany
Krankenanstalt Mutterhaus der Borromäerinnen e.V.
🇩🇪Trier, Rheinland-Pfalz, Germany
Universitätsklinikum Dresden
🇩🇪Dresden, Sachsen, Germany
Städtisches Klinikum Frankfurt-Höchst
🇩🇪Frankfurt, Germany
Katholisches Marienkrankenhaus gGmbH
🇩🇪Hamburg, Germany
University Magdeburg
🇩🇪Magdeburg, Germany
Istituto Europeo di Oncologia
🇮🇹Milano, Italy
Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie, Spólka z o. o.
🇵🇱Kraków, Malopolskie, Poland
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Pomorskie, Poland
Olsztynski Osrodek Onkologiczny "Kopernik" sp. z o. o.
🇵🇱Olsztyn, Warminsko-Mazurskie, Poland
Centrum Onkologii - Instytut im Marii Sklodowskiej-Curie
🇵🇱Warszawa, Poland
State Institution of Healthcare "Arkhangelsk Regional Clinical Oncology Dispensary"
🇷🇺Arkhangelsk, Russian Federation
Cancer Research Center n.a. Blokhin, Chemotherapy Dept.
🇷🇺Moscow, Russian Federation
Non-State Institution of healthcare "Central Clinical Hospital #1 OAO RZD"
🇷🇺Moscow, Russian Federation
State Institution "Blokhin Cancer Research Centre RAMS"
🇷🇺Moscow, Russian Federation
Nizhny Novgorod City Oncology Dispensary
🇷🇺Nizhny Novgorod, Russian Federation
State Healthcare Institution of Omsk Region "Clinical Oncologic Dispensary"
🇷🇺Omsk, Russian Federation
Centro Oncológico Regional de Galicia
🇪🇸A Coruña, La Coruna, Spain
Hospital Nuestra Señora de Sonsoles
🇪🇸Avila, Spain
Hospital Universitario de Girona Doctor Josep Trueta
🇪🇸Gerona, Spain
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Clinico Universitario San Carlos
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Centro Integral Oncológico Clara Campal, Hospital de Madrid Norte-San Chinarro
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Instituto de Investigación Sanitaria
🇪🇸Madrid, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Ospedale Unico Versilia
🇮🇹Lido di Camaiore, Lucca, Italy
Azienda Ospedaliera San Gerardo di Monza
🇮🇹Monza, Monza E Brianza, Italy
Arcispedale Santa Maria Nuova IRCCS
🇮🇹Reggio Emilia, Reggio Nella Emilia, Italy
Ospedale Niguarda CÃ Granda
🇮🇹Milano, Italy
Ospedale Civile SS Annunziata ASL 1
🇮🇹Sassari, Italy
Sharp Health Care
🇺🇸San Diego, California, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
Utah Cancer Specialists
🇺🇸Salt Lake City, Utah, United States
Kaiser Permanente Northwest Region Oncology Hematology
🇺🇸Portland, Oregon, United States
Tennessee Oncology, PLLC
🇺🇸Nashville, Tennessee, United States
Universitätsklinikum der Friedrich-Schiller-Universität Jena
🇩🇪Jena, Thuringen, Germany
Montana Cancer Institute
🇺🇸Missoula, Montana, United States
Centrum Onkologii im. Prof. Franciszka Lukaszczyka w Bydgoszczy
🇵🇱Bydgoszcz, Poland
Centralny Szpital Kliniczny MSWiA
🇵🇱Warszawa, Poland
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Georgetown University
🇺🇸Washington, District of Columbia, United States
Yale University Smilow Cancer Hospital
🇺🇸New Haven, Connecticut, United States
Republican Clinical Oncologic Dispensary of Ministry of health of Republic Tatarstan
🇷🇺Kazan, Russian Federation
Kursk Regional Oncologic Dispensary
🇷🇺Kursk, Russian Federation
N.N.Petrov Research Institute of Oncology
🇷🇺Saint Petersburg, Russian Federation
MD Anderson Cancer Center
🇺🇸Orlando, Florida, United States
Central Coast Medical Oncology Corp
🇺🇸Santa Maria, California, United States