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

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ClinicalTrials.gov Identifier: NCT01479465
Recruitment Status : Terminated
First Posted : November 24, 2011
Results First Posted : April 17, 2019
Last Update Posted : April 17, 2019
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Biological: Simtuzumab Drug: Placebo to match SIM Drug: Leucovorin Drug: Irinotecan Drug: Fluorouracil Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 266 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : December 2011
Actual Primary Completion Date : October 2014
Actual Study Completion Date : February 2015

Arm Intervention/treatment
Experimental: FOLFIRI + SIM 700 mg (Part A)
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.
Biological: Simtuzumab
SIM administered via intravenous infusion over 30 minutes
Other Name: SIM; GS-6624

Drug: Leucovorin
l-Leucovorin 200 mg/m^2 or dl-leucovorin 400 mg/m^2 administered via intravenous infusion over 2 hours
Other Name: Folinic acid

Drug: Irinotecan
Irinotecan 180 mg/m^2 administered via intravenous infusion over 90 minutes

Drug: Fluorouracil
Fluorouracil 400 mg/m^2 administered via intravenous bolus and 2400 mg/m^2 via intravenous infusion over 46 hours

Experimental: FOLFIRI + SIM 200 mg (Part B)
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.
Biological: Simtuzumab
SIM administered via intravenous infusion over 30 minutes
Other Name: SIM; GS-6624

Drug: Leucovorin
l-Leucovorin 200 mg/m^2 or dl-leucovorin 400 mg/m^2 administered via intravenous infusion over 2 hours
Other Name: Folinic acid

Drug: Irinotecan
Irinotecan 180 mg/m^2 administered via intravenous infusion over 90 minutes

Drug: Fluorouracil
Fluorouracil 400 mg/m^2 administered via intravenous bolus and 2400 mg/m^2 via intravenous infusion over 46 hours

Experimental: FOLFIRI + SIM 700 mg (Part B)
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.
Biological: Simtuzumab
SIM administered via intravenous infusion over 30 minutes
Other Name: SIM; GS-6624

Drug: Leucovorin
l-Leucovorin 200 mg/m^2 or dl-leucovorin 400 mg/m^2 administered via intravenous infusion over 2 hours
Other Name: Folinic acid

Drug: Irinotecan
Irinotecan 180 mg/m^2 administered via intravenous infusion over 90 minutes

Drug: Fluorouracil
Fluorouracil 400 mg/m^2 administered via intravenous bolus and 2400 mg/m^2 via intravenous infusion over 46 hours

Experimental: FOLFIRI + Placebo (Part B)
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.
Drug: Placebo to match SIM
Placebo to match SIM administered via intravenous infusion over 30 minutes

Drug: Leucovorin
l-Leucovorin 200 mg/m^2 or dl-leucovorin 400 mg/m^2 administered via intravenous infusion over 2 hours
Other Name: Folinic acid

Drug: Irinotecan
Irinotecan 180 mg/m^2 administered via intravenous infusion over 90 minutes

Drug: Fluorouracil
Fluorouracil 400 mg/m^2 administered via intravenous bolus and 2400 mg/m^2 via intravenous infusion over 46 hours




Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: 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 :
  1. Overall Survival (OS) [ Time Frame: 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.

  2. Objective Response Rate (ORR) [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01479465


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Locations
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United States, Alabama
Clearview Cancer Institute
Huntsville, Alabama, United States, 35801
United States, Arizona
Banner MD Anderson Cancer Center
Gilbert, Arizona, United States
United States, California
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
United States, Connecticut
Yale University Smilow Cancer Hospital
New Haven, Connecticut, United States, 06520
United States, District of Columbia
Georgetown University
Washington, District of Columbia, United States
United States, Florida
Florida Cancer Specialists
Gainesville, Florida, United States
MD Anderson Cancer Center
Orlando, Florida, United States
Florida Cancer Specialists
Saint Petersburg, Florida, United States
United States, Georgia
Peachtree Hematology Oncology Consultants, PC
Atlanta, Georgia, United States
Suburban Hematology Oncology Associates, PC
Lawrenceville, Georgia, United States
United States, Illinois
Northwestern University
Chicago, Illinois, United States
United States, Indiana
Indiana University Simon Cancer Center
Indianapolis, Indiana, United States
United States, Massachusetts
Tufts Medical Center
Boston, Massachusetts, United States, 02111
Dana Farber Cancer Institute
Boston, Massachusetts, United States
United States, Michigan
West Michigan Cancer Center
Kalamazoo, Michigan, United States
United States, Mississippi
Hematology and Oncology Associates at BridgePoint
Tupelo, Mississippi, United States
United States, Missouri
Saint Joseph Oncology, Inc.
Saint Joseph, Missouri, United States
United States, Montana
Montana Cancer Institute
Missoula, Montana, United States, 59802
United States, Nebraska
Southeast Nebraska Cancer Center
Lincoln, Nebraska, United States
United States, Nevada
Comprehensive Cancer Centers of Nevada
Henderson, Nevada, United States
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, United States
United States, New York
New York University Clinical Cancer Center
New York, New York, United States, 10016
United States, Ohio
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
United States, Oregon
Kaiser Permanente Northwest Region Oncology Hematology
Portland, Oregon, United States
United States, South Carolina
South Carolina Oncology Associates
Columbia, South Carolina, United States
United States, Tennessee
Tennessee Oncology, PLLC
Nashville, Tennessee, United States
United States, Texas
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, 76508
The Center for Cancer and Blood Disorders
Weatherford, Texas, United States
United States, Utah
Intermountain Healthcare
Saint George, Utah, United States
Utah Cancer Specialists
Salt Lake City, Utah, United States
United States, Virginia
Virginal Cancer Specialists, PC
Fairfax, Virginia, United States, 22033
Virginia Cancer Institute
Midlothian, Virginia, United States
Virginia Cancer Institute
Richmond, Virginia, United States
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States
France
Centre Hospitalier Universitaire Estaing
Clermont Ferrand, Auvergne, France, 63003
Centre Eugène Marquis
Rennes Cedex, Bretagne, France, 35042
Centre Georges François Leclerc
Dijon, France
Centre Oscar Lambret, Dept. de Cancerologie Digestive et Urologique
Lille Cedex, France
Centre Hospitalier Régional Universitaire Hôpital Saint Eloi
Montpellier Cedex 5, France
Centre Antoine Lacassagne
Nice Cedex 2, France
Institut Paoli Calmettes Centre Régional de Lutte Contre le Cancer
Rennes Cedex, France
Hôpital Trousseau - Service de Gastroenterologie
Tours, France
Germany
Universitätsklinikum Ulm
Ulm, Baden-Wuerttemberg, Germany, 89081
Universitätsklinikums Mannheim
Mannheim, Baden-Wuerttenberg, Germany, 68167
Ludwig-Maximilians-Universität München Klinikum Großhadern
München, Bayern, Germany, 81377
Universitätsklinikum Rostock
Rostock, Mecklenburg-Vorpommern, Germany, 18055
Klinikum Region Hannover GmbH, Krankenhaus Siloah
Hannover, Niedersachsen, Germany, 30449
Medizinische Universitätsklinik Bochum
Bochum, Nordrhein-Westfalen, Germany, 44892
Universitätsklinikum Essen
Essen, Nordrhein-Westfalen, Germany, 45122
Krankenanstalt Mutterhaus der Borromäerinnen e.V.
Trier, Rheinland-Pfalz, Germany, 54290
Universitätsklinikum Dresden
Dresden, Sachsen, Germany, 01307
Universitätsklinikum der Friedrich-Schiller-Universität Jena
Jena, Thuringen, Germany, 07747
Städtisches Klinikum Frankfurt-Höchst
Frankfurt, Germany
Katholisches Marienkrankenhaus gGmbH
Hamburg, Germany, 22045
University Magdeburg
Magdeburg, Germany
Italy
Ospedale Unico Versilia
Lido di Camaiore, Lucca, Italy, 55043
Azienda Ospedaliera San Gerardo di Monza
Monza, Monza E Brianza, Italy, 20052
Arcispedale Santa Maria Nuova IRCCS
Reggio Emilia, Reggio Nella Emilia, Italy, 42100
Istituto Europeo di Oncologia
Milano, Italy, 20141
Ospedale Niguarda Cà Granda
Milano, Italy, 20162
Ospedale Civile SS Annunziata ASL 1
Sassari, Italy, 07100
Poland
Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie, Spólka z o. o.
Kraków, Malopolskie, Poland, 31-826
Uniwersyteckie Centrum Kliniczne
Gdansk, Pomorskie, Poland, 80-952
Olsztynski Osrodek Onkologiczny "Kopernik" sp. z o. o.
Olsztyn, Warminsko-Mazurskie, Poland, 10-513
Centrum Onkologii im. Prof. Franciszka Lukaszczyka w Bydgoszczy
Bydgoszcz, Poland
Centralny Szpital Kliniczny MSWiA
Warszawa, Poland
Centrum Onkologii - Instytut im Marii Sklodowskiej-Curie
Warszawa, Poland
Russian Federation
State Institution of Healthcare "Arkhangelsk Regional Clinical Oncology Dispensary"
Arkhangelsk, Russian Federation
Republican Clinical Oncologic Dispensary of Ministry of health of Republic Tatarstan
Kazan, Russian Federation
Kursk Regional Oncologic Dispensary
Kursk, 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
N.N.Petrov Research Institute of Oncology
Saint Petersburg, Russian Federation
Spain
Centro Oncológico Regional de Galicia
A Coruña, La Coruna, Spain, 15009
Hospital Nuestra Señora de Sonsoles
Avila, Spain, 05004
Hospital Universitario Vall d'Hebron
Barcelona, Spain, 08035
Hospital Universitario de Girona Doctor Josep Trueta
Gerona, Spain, 17007
Hospital Universitario Ramón y Cajal
Madrid, Spain, 28034
Hospital Clinico Universitario San Carlos
Madrid, Spain, 28040
Hospital Universitario 12 de Octubre
Madrid, Spain, 28041
Centro Integral Oncológico Clara Campal, Hospital de Madrid Norte-San Chinarro
Madrid, Spain, 28050
Hospital Universitario La Paz
Madrid, Spain
Instituto de Investigación Sanitaria
Madrid, Spain
Hospital Clinico Universitario de Valencia
Valencia, Spain, 46010
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Zung Thai, MD Gilead Sciences

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01479465     History of Changes
Other Study ID Numbers: GS-US-295-0203
2011-003754-61 ( EudraCT Number )
First Posted: November 24, 2011    Key Record Dates
Results First Posted: April 17, 2019
Last Update Posted: April 17, 2019
Last Verified: March 2019
Keywords provided by Gilead Sciences:
GSI
Gilead
Gilead Sciences
GS-6624
Colorectal Cancer
KRAS
Oncology
monoclonal antibody
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Colonic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Carcinoma
Irinotecan
Fluorouracil
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs