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

NCT ID: NCT01479465

Last Updated: 2019-04-17

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

266 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-12-31

Study Completion Date

2015-02-28

Brief Summary

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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

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Conditions

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Colorectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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.

Group Type EXPERIMENTAL

Simtuzumab

Intervention Type BIOLOGICAL

SIM administered via intravenous infusion over 30 minutes

Leucovorin

Intervention Type DRUG

l-Leucovorin 200 mg/m\^2 or dl-leucovorin 400 mg/m\^2 administered via intravenous infusion over 2 hours

Irinotecan

Intervention Type DRUG

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

Fluorouracil

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

Simtuzumab

Intervention Type BIOLOGICAL

SIM administered via intravenous infusion over 30 minutes

Leucovorin

Intervention Type DRUG

l-Leucovorin 200 mg/m\^2 or dl-leucovorin 400 mg/m\^2 administered via intravenous infusion over 2 hours

Irinotecan

Intervention Type DRUG

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

Fluorouracil

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

Simtuzumab

Intervention Type BIOLOGICAL

SIM administered via intravenous infusion over 30 minutes

Leucovorin

Intervention Type DRUG

l-Leucovorin 200 mg/m\^2 or dl-leucovorin 400 mg/m\^2 administered via intravenous infusion over 2 hours

Irinotecan

Intervention Type DRUG

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

Fluorouracil

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

Placebo to match SIM

Intervention Type DRUG

Placebo to match SIM administered via intravenous infusion over 30 minutes

Leucovorin

Intervention Type DRUG

l-Leucovorin 200 mg/m\^2 or dl-leucovorin 400 mg/m\^2 administered via intravenous infusion over 2 hours

Irinotecan

Intervention Type DRUG

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

Fluorouracil

Intervention Type DRUG

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

Interventions

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Simtuzumab

SIM administered via intravenous infusion over 30 minutes

Intervention Type BIOLOGICAL

Placebo to match SIM

Placebo to match SIM administered via intravenous infusion over 30 minutes

Intervention Type DRUG

Leucovorin

l-Leucovorin 200 mg/m\^2 or dl-leucovorin 400 mg/m\^2 administered via intravenous infusion over 2 hours

Intervention Type DRUG

Irinotecan

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

Intervention Type DRUG

Fluorouracil

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

Intervention Type DRUG

Other Intervention Names

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SIM; GS-6624 Folinic acid

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Zung Thai, MD

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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Clearview Cancer Institute

Huntsville, Alabama, United States

Site Status

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Site Status

Central Hematology Oncology Medical Group, Inc.

Alhambra, California, United States

Site Status

Comprehensive Blood and Cancer Center

Bakersfield, California, United States

Site Status

Providence Saint Joseph Medical Center-Disney Family Cancer Center

Burbank, California, United States

Site Status

Wilshire Oncology Medical Group, Inc.

Corona, California, United States

Site Status

Saint Jude Heritage Healthcare

Fullerton, California, United States

Site Status

University of California San Diego Medical Center

La Jolla, California, United States

Site Status

Pacific Shores Medical Group

Long Beach, California, United States

Site Status

Comprehensive Hematology Oncology Centers, Inc.

Los Angeles, California, United States

Site Status

TORI Network (Translational Oncology Research Intl)

Los Angeles, California, United States

Site Status

UCLA Community Oncology Practice

Los Angeles, California, United States

Site Status

Stanford University Medical Center

Palo Alto, California, United States

Site Status

Wilshire Oncology Medical Group, Inc.

Pomona, California, United States

Site Status

Cancer Care Associates Medical Group

Redondo Beach, California, United States

Site Status

Pacific Shores Medical Group

Redondo Beach, California, United States

Site Status

Sharp Health Care

San Diego, California, United States

Site Status

San Jose Medical Group

San Jose, California, United States

Site Status

Central Coast Medical Oncology Corp

Santa Maria, California, United States

Site Status

Yale University Smilow Cancer Hospital

New Haven, Connecticut, United States

Site Status

Georgetown University

Washington D.C., District of Columbia, United States

Site Status

Florida Cancer Specialists

Gainesville, Florida, United States

Site Status

MD Anderson Cancer Center

Orlando, Florida, United States

Site Status

Florida Cancer Specialists

St. Petersburg, Florida, United States

Site Status

Peachtree Hematology Oncology Consultants, PC

Atlanta, Georgia, United States

Site Status

Suburban Hematology Oncology Associates, PC

Lawrenceville, Georgia, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Indiana University Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

Tufts Medical Center

Boston, Massachusetts, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

West Michigan Cancer Center

Kalamazoo, Michigan, United States

Site Status

Hematology and Oncology Associates at BridgePoint

Tupelo, Mississippi, United States

Site Status

Saint Joseph Oncology, Inc.

Saint Joseph, Missouri, United States

Site Status

Montana Cancer Institute

Missoula, Montana, United States

Site Status

Southeast Nebraska Cancer Center

Lincoln, Nebraska, United States

Site Status

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, United States

Site Status

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Site Status

New York University Clinical Cancer Center

New York, New York, United States

Site Status

Oncology Hematology Care, Inc.

Cincinnati, Ohio, United States

Site Status

Signal Point Clinical Research Center, LLC

Middletown, Ohio, United States

Site Status

Oncology Hematology Care, Inc.

Wilmington, Ohio, United States

Site Status

Kaiser Permanente Northwest Region Oncology Hematology

Portland, Oregon, United States

Site Status

South Carolina Oncology Associates

Columbia, South Carolina, United States

Site Status

Tennessee Oncology, PLLC

Nashville, Tennessee, United States

Site Status

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, United States

Site Status

Center for Cancer and Blood Disorders, PC

Fort Worth, Texas, United States

Site Status

Joe Arrington Cancer Research and Treatment Center

Lubbock, Texas, United States

Site Status

Scott & White Memorial

Temple, Texas, United States

Site Status

The Center for Cancer and Blood Disorders

Weatherford, Texas, United States

Site Status

Utah Cancer Specialists

Salt Lake City, Utah, United States

Site Status

Intermountain Healthcare

St. George, Utah, United States

Site Status

Virginal Cancer Specialists, PC

Fairfax, Virginia, United States

Site Status

Virginia Cancer Institute

Midlothian, Virginia, United States

Site Status

Virginia Cancer Institute

Richmond, Virginia, United States

Site Status

Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

University of Wisconsin

Madison, Wisconsin, United States

Site Status

Centre Hospitalier Universitaire Estaing

Clermont-Ferrand, Auvergne, France

Site Status

Centre Eugène Marquis

Rennes, Brittany Region, France

Site Status

Centre Georges François Leclerc

Dijon, , France

Site Status

Centre Oscar Lambret, Dept. de Cancerologie Digestive et Urologique

Lille, , France

Site Status

Centre Hospitalier Régional Universitaire Hôpital Saint Eloi

Montpellier, , France

Site Status

Centre Antoine Lacassagne

Nice, , France

Site Status

Institut Paoli Calmettes Centre Régional de Lutte Contre le Cancer

Rennes, , France

Site Status

Hôpital Trousseau - Service de Gastroenterologie

Tours, , France

Site Status

Universitätsklinikums Mannheim

Mannheim, Baden-Wuerttenberg, Germany

Site Status

Universitätsklinikum Ulm

Ulm, Baden-Wurttemberg, Germany

Site Status

Ludwig-Maximilians-Universität München Klinikum Großhadern

München, Bavaria, Germany

Site Status

Klinikum Region Hannover GmbH, Krankenhaus Siloah

Hanover, Lower Saxony, Germany

Site Status

Universitätsklinikum Rostock

Rostock, Mecklenburg-Vorpommern, Germany

Site Status

Medizinische Universitätsklinik Bochum

Bochum, North Rhine-Westphalia, Germany

Site Status

Universitätsklinikum Essen

Essen, North Rhine-Westphalia, Germany

Site Status

Krankenanstalt Mutterhaus der Borromäerinnen e.V.

Trier, Rhineland-Palatinate, Germany

Site Status

Universitätsklinikum Dresden

Dresden, Saxony, Germany

Site Status

Universitätsklinikum der Friedrich-Schiller-Universität Jena

Jena, Thuringia, Germany

Site Status

Städtisches Klinikum Frankfurt-Höchst

Frankfurt, , Germany

Site Status

Katholisches Marienkrankenhaus gGmbH

Hamburg, , Germany

Site Status

University Magdeburg

Magdeburg, , Germany

Site Status

Ospedale Unico Versilia

Lido di Camaiore, Lucca, Italy

Site Status

Azienda Ospedaliera San Gerardo di Monza

Monza, Monza E Brianza, Italy

Site Status

Arcispedale Santa Maria Nuova IRCCS

Reggio Emilia, Reggio Nella Emilia, Italy

Site Status

Istituto Europeo di Oncologia

Milan, , Italy

Site Status

Ospedale Niguarda Cà Granda

Milan, , Italy

Site Status

Ospedale Civile SS Annunziata ASL 1

Sassari, , Italy

Site Status

Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie, Spólka z o. o.

Krakow, Lesser Poland Voivodeship, Poland

Site Status

Uniwersyteckie Centrum Kliniczne

Gdansk, Pomeranian Voivodeship, Poland

Site Status

Olsztynski Osrodek Onkologiczny "Kopernik" sp. z o. o.

Olsztyn, Warmian-Masurian Voivodeship, Poland

Site Status

Centrum Onkologii im. Prof. Franciszka Lukaszczyka w Bydgoszczy

Bydgoszcz, , Poland

Site Status

Centralny Szpital Kliniczny MSWiA

Warsaw, , Poland

Site Status

Centrum Onkologii - Instytut im Marii Sklodowskiej-Curie

Warsaw, , Poland

Site Status

State Institution of Healthcare "Arkhangelsk Regional Clinical Oncology Dispensary"

Arkhangelsk, , Russia

Site Status

Republican Clinical Oncologic Dispensary of Ministry of health of Republic Tatarstan

Kazan', , Russia

Site Status

Kursk Regional Oncologic Dispensary

Kursk, , Russia

Site Status

Cancer Research Center n.a. Blokhin, Chemotherapy Dept.

Moscow, , Russia

Site Status

Non-State Institution of healthcare "Central Clinical Hospital #1 OAO RZD"

Moscow, , Russia

Site Status

State Institution "Blokhin Cancer Research Centre RAMS"

Moscow, , Russia

Site Status

Nizhny Novgorod City Oncology Dispensary

Nizhny Novgorod, , Russia

Site Status

State Healthcare Institution of Omsk Region "Clinical Oncologic Dispensary"

Omsk, , Russia

Site Status

N.N.Petrov Research Institute of Oncology

Saint Petersburg, , Russia

Site Status

Centro Oncológico Regional de Galicia

A Coruña, La Coruna, Spain

Site Status

Hospital Nuestra Señora de Sonsoles

Ávila, , Spain

Site Status

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Universitario de Girona Doctor Josep Trueta

Girona, , Spain

Site Status

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Site Status

Hospital Clinico Universitario San Carlos

Madrid, , Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Centro Integral Oncológico Clara Campal, Hospital de Madrid Norte-San Chinarro

Madrid, , Spain

Site Status

Hospital Universitario La Paz

Madrid, , Spain

Site Status

Instituto de Investigación Sanitaria

Madrid, , Spain

Site Status

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Site Status

Countries

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United States France Germany Italy Poland Russia Spain

References

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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.

Reference Type DERIVED
PMID: 28246207 (View on PubMed)

Other Identifiers

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2011-003754-61

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-295-0203

Identifier Type: -

Identifier Source: org_study_id

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