Clinical trial NCT01479465: Efficacy and Safety of Simtuzumab (SIM) With FOLFIRI as Second Line Treatment in Colorectal Adenocarcinoma
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: GSI
Gilead
Gilead Sciences
GS-6624
Colorectal Cancer
KRAS
Oncology
monoclonal antibody
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2011-11-24
Enrollment: 266
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Randomization up to 27 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Randomization up to 33 months
measure: Objective Response Rate (ORR)
timeFrame: Randomization up to 27 months
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Clearview Cancer Institute
state: Alabama
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Alhambra
country: United States
facility: Central Hematology Oncology Medical Group, Inc.
state: California
city: Bakersfield
country: United States
facility: Comprehensive Blood and Cancer Center
state: California
city: Burbank
country: United States
facility: Providence Saint Joseph Medical Center-Disney Family Cancer Center
state: California
city: Corona
country: United States
facility: Wilshire Oncology Medical Group, Inc.
state: California
city: Fullerton
country: United States
facility: Saint Jude Heritage Healthcare
state: California
city: La Jolla
country: United States
facility: University of California San Diego Medical Center
state: California
city: Long Beach
country: United States
facility: Pacific Shores Medical Group
state: California
city: Los Angeles
country: United States
facility: Comprehensive Hematology Oncology Centers, Inc.
state: California
city: Los Angeles
country: United States
facility: TORI Network (Translational Oncology Research Intl)
state: California
city: Los Angeles
country: United States
facility: UCLA Community Oncology Practice
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: Pomona
country: United States
facility: Wilshire Oncology Medical Group, Inc.
state: California
city: Redondo Beach
country: United States
facility: Cancer Care Associates Medical Group
state: California
city: Redondo Beach
country: United States
facility: Pacific Shores Medical Group
state: California
city: San Diego
country: United States
facility: Sharp Health Care
state: California
city: San Jose
country: United States
facility: San Jose Medical Group
state: California
city: Santa Maria
country: United States
facility: Central Coast Medical Oncology Corp
state: California
city: New Haven
country: United States
facility: Yale University Smilow Cancer Hospital
state: Connecticut
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Gainesville
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Orlando
country: United States
facility: MD Anderson Cancer Center
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Atlanta
country: United States
facility: Peachtree Hematology Oncology Consultants, PC
state: Georgia
city: Lawrenceville
country: United States
facility: Suburban Hematology Oncology Associates, PC
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Simon Cancer Center
state: Indiana
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Tupelo
country: United States
facility: Hematology and Oncology Associates at BridgePoint
state: Mississippi
city: Saint Joseph
country: United States
facility: Saint Joseph Oncology, Inc.
state: Missouri
city: Missoula
country: United States
facility: Montana Cancer Institute
state: Montana
city: Lincoln
country: United States
facility: Southeast Nebraska Cancer Center
state: Nebraska
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: New York
country: United States
facility: New York University Clinical Cancer Center
state: New York
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc.
state: Ohio
city: Middletown
country: United States
facility: Signal Point Clinical Research Center, LLC
state: Ohio
city: Wilmington
country: United States
facility: Oncology Hematology Care, Inc.
state: Ohio
city: Portland
country: United States
facility: Kaiser Permanente Northwest Region Oncology Hematology
state: Oregon
city: Columbia
country: United States
facility: South Carolina Oncology Associates
state: South Carolina
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center at Dallas
state: Texas
city: Fort Worth
country: United States
facility: Center for Cancer and Blood Disorders, PC
state: Texas
city: Lubbock
country: United States
facility: Joe Arrington Cancer Research and Treatment Center
state: Texas
city: Temple
country: United States
facility: Scott & White Memorial
state: Texas
city: Weatherford
country: United States
facility: The Center for Cancer and Blood Disorders
state: Texas
city: Saint George
country: United States
facility: Intermountain Healthcare
state: Utah
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists
state: Utah
city: Fairfax
country: United States
facility: Virginal Cancer Specialists, PC
state: Virginia
city: Midlothian
country: United States
facility: Virginia Cancer Institute
state: Virginia
city: Richmond
country: United States
facility: Virginia Cancer Institute
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Clermont Ferrand
country: France
facility: Centre Hospitalier Universitaire Estaing
state: Auvergne
city: Rennes Cedex
country: France
facility: Centre Eugène Marquis
state: Bretagne
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Lille Cedex
country: France
facility: Centre Oscar Lambret, Dept. de Cancerologie Digestive et Urologique
city: Montpellier Cedex 5
country: France
facility: Centre Hospitalier Régional Universitaire Hôpital Saint Eloi
city: Nice Cedex 2
country: France
facility: Centre Antoine Lacassagne
city: Rennes Cedex
country: France
facility: Institut Paoli Calmettes Centre Régional de Lutte Contre le Cancer
city: Tours
country: France
facility: Hôpital Trousseau - Service de Gastroenterologie
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
state: Baden-Wuerttemberg
city: Mannheim
country: Germany
facility: Universitätsklinikums Mannheim
state: Baden-Wuerttenberg
city: München
country: Germany
facility: Ludwig-Maximilians-Universität München Klinikum Großhadern
state: Bayern
city: Rostock
country: Germany
facility: Universitätsklinikum Rostock
state: Mecklenburg-Vorpommern
city: Hannover
country: Germany
facility: Klinikum Region Hannover GmbH, Krankenhaus Siloah
state: Niedersachsen
city: Bochum
country: Germany
facility: Medizinische Universitätsklinik Bochum
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: Universitätsklinikum Essen
state: Nordrhein-Westfalen
city: Trier
country: Germany
facility: Krankenanstalt Mutterhaus der Borromäerinnen e.V.
state: Rheinland-Pfalz
city: Dresden
country: Germany
facility: Universitätsklinikum Dresden
state: Sachsen
city: Jena
country: Germany
facility: Universitätsklinikum der Friedrich-Schiller-Universität Jena
state: Thuringen
city: Frankfurt
country: Germany
facility: Städtisches Klinikum Frankfurt-Höchst
city: Hamburg
country: Germany
facility: Katholisches Marienkrankenhaus gGmbH
city: Magdeburg
country: Germany
facility: University Magdeburg
city: Lido di Camaiore
country: Italy
facility: Ospedale Unico Versilia
state: Lucca
city: Monza
country: Italy
facility: Azienda Ospedaliera San Gerardo di Monza
state: Monza E Brianza
city: Reggio Emilia
country: Italy
facility: Arcispedale Santa Maria Nuova IRCCS
state: Reggio Nella Emilia
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Milano
country: Italy
facility: Ospedale Niguarda Cà Granda
city: Sassari
country: Italy
facility: Ospedale Civile SS Annunziata ASL 1
city: Kraków
country: Poland
facility: Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie, Spólka z o. o.
state: Malopolskie
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
state: Pomorskie
city: Olsztyn
country: Poland
facility: Olsztynski Osrodek Onkologiczny "Kopernik" sp. z o. o.
state: Warminsko-Mazurskie
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii im. Prof. Franciszka Lukaszczyka w Bydgoszczy
city: Warszawa
country: Poland
facility: Centralny Szpital Kliniczny MSWiA
city: Warszawa
country: Poland
facility: Centrum Onkologii - Instytut im Marii Sklodowskiej-Curie
city: Arkhangelsk
country: Russian Federation
facility: State Institution of Healthcare "Arkhangelsk Regional Clinical Oncology Dispensary"
city: Kazan
country: Russian Federation
facility: Republican Clinical Oncologic Dispensary of Ministry of health of Republic Tatarstan
city: Kursk
country: Russian Federation
facility: Kursk Regional Oncologic Dispensary
city: Moscow
country: Russian Federation
facility: Cancer Research Center n.a. Blokhin, Chemotherapy Dept.
city: Moscow
country: Russian Federation
facility: Non-State Institution of healthcare "Central Clinical Hospital #1 OAO RZD"
city: Moscow
country: Russian Federation
facility: State Institution "Blokhin Cancer Research Centre RAMS"
city: Nizhny Novgorod
country: Russian Federation
facility: Nizhny Novgorod City Oncology Dispensary
city: Omsk
country: Russian Federation
facility: State Healthcare Institution of Omsk Region "Clinical Oncologic Dispensary"
city: Saint Petersburg
country: Russian Federation
facility: N.N.Petrov Research Institute of Oncology
city: A Coruña
country: Spain
facility: Centro Oncológico Regional de Galicia
state: La Coruna
city: Avila
country: Spain
facility: Hospital Nuestra Señora de Sonsoles
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Gerona
country: Spain
facility: Hospital Universitario de Girona Doctor Josep Trueta
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Clinico Universitario San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Centro Integral Oncológico Clara Campal, Hospital de Madrid Norte-San Chinarro
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Instituto de Investigación Sanitaria
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
Study officials:
affiliation: Gilead Sciences
name: Zung Thai, MD
role: STUDY_DIRECTOR
References:
citation: 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.