Efficacy and Safety of Simtuzumab (SIM) With FOLFIRI as Second Line Treatment in Colorectal Adenocarcinoma
A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of GS-6624 Combined With FOLFIRI as Second Line Treatment for Metastatic KRAS Mutant Colorectal Adenocarcinoma That Has Progressed Following a First Line Oxaliplatin- and Fluoropyrimidine-Containing Regimen
2 other identifiers
interventional
266
7 countries
109
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 colorectal-cancer
Started Dec 2011
109 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 9, 2011
CompletedFirst Posted
Study publicly available on registry
November 24, 2011
CompletedStudy Start
First participant enrolled
December 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
February 1, 2015
CompletedResults Posted
Study results publicly available
April 17, 2019
CompletedApril 17, 2019
March 1, 2019
2.8 years
November 9, 2011
March 26, 2019
March 26, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression Free Survival (PFS)
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.
Randomization up to 27 months
Secondary Outcomes (2)
Overall Survival (OS)
Randomization up to 33 months
Objective Response Rate (ORR)
Randomization up to 27 months
Study Arms (4)
FOLFIRI + SIM 700 mg (Part A)
EXPERIMENTALParticipants 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)
EXPERIMENTALParticipants 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)
EXPERIMENTALParticipants 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)
EXPERIMENTALParticipants 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.
Interventions
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
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Gilead Scienceslead
Study Sites (109)
Clearview Cancer Institute
Huntsville, Alabama, 35801, 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.
Corona, 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
Long 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
Wilshire Oncology Medical Group, Inc.
Pomona, California, United States
Cancer Care Associates Medical Group
Redondo Beach, California, United States
Pacific Shores Medical Group
Redondo Beach, California, United States
Sharp Health Care
San Diego, California, United States
San Jose Medical Group
San Jose, California, United States
Central Coast Medical Oncology Corp
Santa Maria, California, United States
Yale University Smilow Cancer Hospital
New Haven, Connecticut, 06520, United States
Georgetown University
Washington D.C., District of Columbia, United States
Florida Cancer Specialists
Gainesville, Florida, United States
MD Anderson Cancer Center
Orlando, Florida, United States
Florida Cancer Specialists
St. 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
Tufts Medical Center
Boston, Massachusetts, 02111, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
West Michigan Cancer Center
Kalamazoo, Michigan, United States
Hematology and Oncology Associates at BridgePoint
Tupelo, Mississippi, United States
Saint Joseph Oncology, Inc.
Saint Joseph, Missouri, United States
Montana Cancer Institute
Missoula, Montana, 59802, United States
Southeast Nebraska Cancer Center
Lincoln, Nebraska, United States
Comprehensive Cancer Centers of Nevada
Henderson, Nevada, United States
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, United States
New York University Clinical Cancer Center
New York, New York, 10016, United States
Oncology Hematology Care, Inc.
Cincinnati, Ohio, United States
Signal Point Clinical Research Center, LLC
Middletown, Ohio, United States
Oncology Hematology Care, Inc.
Wilmington, Ohio, United States
Kaiser Permanente Northwest Region Oncology Hematology
Portland, Oregon, United States
South Carolina Oncology Associates
Columbia, South Carolina, United States
Tennessee Oncology, PLLC
Nashville, Tennessee, 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, 76508, United States
The Center for Cancer and Blood Disorders
Weatherford, Texas, United States
Utah Cancer Specialists
Salt Lake City, Utah, United States
Intermountain Healthcare
St. George, Utah, United States
Virginal Cancer Specialists, PC
Fairfax, Virginia, 22033, United States
Virginia Cancer Institute
Midlothian, Virginia, United States
Virginia Cancer Institute
Richmond, Virginia, United States
Seattle Cancer Care Alliance
Seattle, Washington, United States
University of Wisconsin
Madison, Wisconsin, United States
Centre Hospitalier Universitaire Estaing
Clermont-Ferrand, Auvergne, 63003, France
Centre Eugène Marquis
Rennes, Brittany Region, 35042, France
Centre Georges François Leclerc
Dijon, France
Centre Oscar Lambret, Dept. de Cancerologie Digestive et Urologique
Lille, France
Centre Hospitalier Régional Universitaire Hôpital Saint Eloi
Montpellier, France
Centre Antoine Lacassagne
Nice, France
Institut Paoli Calmettes Centre Régional de Lutte Contre le Cancer
Rennes, France
Hôpital Trousseau - Service de Gastroenterologie
Tours, France
Universitätsklinikums Mannheim
Mannheim, Baden-Wuerttenberg, 68167, Germany
Universitätsklinikum Ulm
Ulm, Baden-Wurttemberg, 89081, Germany
Ludwig-Maximilians-Universität München Klinikum Großhadern
München, Bavaria, 81377, Germany
Klinikum Region Hannover GmbH, Krankenhaus Siloah
Hanover, Lower Saxony, 30449, Germany
Universitätsklinikum Rostock
Rostock, Mecklenburg-Vorpommern, 18055, Germany
Medizinische Universitätsklinik Bochum
Bochum, North Rhine-Westphalia, 44892, Germany
Universitätsklinikum Essen
Essen, North Rhine-Westphalia, 45122, Germany
Krankenanstalt Mutterhaus der Borromäerinnen e.V.
Trier, Rhineland-Palatinate, 54290, Germany
Universitätsklinikum Dresden
Dresden, Saxony, 01307, Germany
Universitätsklinikum der Friedrich-Schiller-Universität Jena
Jena, Thuringia, 07747, Germany
Städtisches Klinikum Frankfurt-Höchst
Frankfurt, Germany
Katholisches Marienkrankenhaus gGmbH
Hamburg, 22045, Germany
University Magdeburg
Magdeburg, Germany
Ospedale Unico Versilia
Lido di Camaiore, Lucca, 55043, Italy
Azienda Ospedaliera San Gerardo di Monza
Monza, Monza E Brianza, 20052, Italy
Arcispedale Santa Maria Nuova IRCCS
Reggio Emilia, Reggio Nella Emilia, 42100, Italy
Istituto Europeo di Oncologia
Milan, 20141, Italy
Ospedale Niguarda Cà Granda
Milan, 20162, Italy
Ospedale Civile SS Annunziata ASL 1
Sassari, 07100, Italy
Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie, Spólka z o. o.
Krakow, Lesser Poland Voivodeship, 31-826, Poland
Uniwersyteckie Centrum Kliniczne
Gdansk, Pomeranian Voivodeship, 80-952, Poland
Olsztynski Osrodek Onkologiczny "Kopernik" sp. z o. o.
Olsztyn, Warmian-Masurian Voivodeship, 10-513, Poland
Centrum Onkologii im. Prof. Franciszka Lukaszczyka w Bydgoszczy
Bydgoszcz, Poland
Centralny Szpital Kliniczny MSWiA
Warsaw, Poland
Centrum Onkologii - Instytut im Marii Sklodowskiej-Curie
Warsaw, Poland
State Institution of Healthcare "Arkhangelsk Regional Clinical Oncology Dispensary"
Arkhangelsk, Russia
Republican Clinical Oncologic Dispensary of Ministry of health of Republic Tatarstan
Kazan', Russia
Kursk Regional Oncologic Dispensary
Kursk, Russia
Cancer Research Center n.a. Blokhin, Chemotherapy Dept.
Moscow, Russia
Non-State Institution of healthcare "Central Clinical Hospital #1 OAO RZD"
Moscow, Russia
State Institution "Blokhin Cancer Research Centre RAMS"
Moscow, Russia
Nizhny Novgorod City Oncology Dispensary
Nizhny Novgorod, Russia
State Healthcare Institution of Omsk Region "Clinical Oncologic Dispensary"
Omsk, Russia
N.N.Petrov Research Institute of Oncology
Saint Petersburg, Russia
Centro Oncológico Regional de Galicia
A Coruña, La Coruna, 15009, Spain
Hospital Nuestra Señora de Sonsoles
Ávila, 05004, Spain
Hospital Universitario Vall d'Hebron
Barcelona, 08035, Spain
Hospital Universitario de Girona Doctor Josep Trueta
Girona, 17007, Spain
Hospital Universitario Ramón y Cajal
Madrid, 28034, Spain
Hospital Clinico Universitario San Carlos
Madrid, 28040, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Centro Integral Oncológico Clara Campal, Hospital de Madrid Norte-San Chinarro
Madrid, 28050, Spain
Hospital Universitario La Paz
Madrid, Spain
Instituto de Investigación Sanitaria
Madrid, Spain
Hospital Clinico Universitario de Valencia
Valencia, 46010, Spain
Related Publications (1)
Hecht JR, Benson AB 3rd, Vyushkov D, Yang Y, Bendell J, Verma U. A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Simtuzumab in Combination with FOLFIRI for the Second-Line Treatment of Metastatic KRAS Mutant Colorectal Adenocarcinoma. Oncologist. 2017 Mar;22(3):243-e23. doi: 10.1634/theoncologist.2016-0479. Epub 2017 Feb 28.
PMID: 28246207DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Gilead Clinical Study Information Center
- Organization
- Gilead Sciences
Study Officials
- STUDY DIRECTOR
Zung Thai, MD
Gilead Sciences
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 9, 2011
First Posted
November 24, 2011
Study Start
December 1, 2011
Primary Completion
October 1, 2014
Study Completion
February 1, 2015
Last Updated
April 17, 2019
Results First Posted
April 17, 2019
Record last verified: 2019-03