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

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01479465
• Other study ID #: GS-US-295-0203
• Secondary ID: 2011-003754-61
• Status: Terminated
• Phase: Phase 2
• Start date: December 2011
• Est. completion date: February 2015

Study information

• Verified date: March 2019
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 266
• Est. completion date: February 2015
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Biological:
• Simtuzumab
SIM administered via intravenous infusion over 30 minutes

Drug:
• Placebo to match SIM
Placebo to match SIM administered via intravenous infusion over 30 minutes
• Leucovorin
l-Leucovorin 200 mg/m^2 or dl-leucovorin 400 mg/m^2 administered via intravenous infusion over 2 hours
• Irinotecan
Irinotecan 180 mg/m^2 administered via intravenous infusion over 90 minutes
• Fluorouracil
Fluorouracil 400 mg/m^2 administered via intravenous bolus and 2400 mg/m^2 via intravenous infusion over 46 hours

Locations

Country	Name	City	State
France	Centre Hospitalier Universitaire Estaing	Clermont Ferrand	Auvergne
France	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	Centre Eugène Marquis	Rennes Cedex	Bretagne
France	Institut Paoli Calmettes Centre Régional de Lutte Contre le Cancer	Rennes Cedex
France	Hôpital Trousseau - Service de Gastroenterologie	Tours
Germany	Medizinische Universitätsklinik Bochum	Bochum	Nordrhein-Westfalen
Germany	Universitätsklinikum Dresden	Dresden	Sachsen
Germany	Universitätsklinikum Essen	Essen	Nordrhein-Westfalen
Germany	Städtisches Klinikum Frankfurt-Höchst	Frankfurt
Germany	Katholisches Marienkrankenhaus gGmbH	Hamburg
Germany	Klinikum Region Hannover GmbH, Krankenhaus Siloah	Hannover	Niedersachsen
Germany	Universitätsklinikum der Friedrich-Schiller-Universität Jena	Jena	Thuringen
Germany	University Magdeburg	Magdeburg
Germany	Universitätsklinikums Mannheim	Mannheim	Baden-Wuerttenberg
Germany	Ludwig-Maximilians-Universität München Klinikum Großhadern	München	Bayern
Germany	Universitätsklinikum Rostock	Rostock	Mecklenburg-Vorpommern
Germany	Krankenanstalt Mutterhaus der Borromäerinnen e.V.	Trier	Rheinland-Pfalz
Germany	Universitätsklinikum Ulm	Ulm	Baden-Wuerttemberg
Italy	Ospedale Unico Versilia	Lido di Camaiore	Lucca
Italy	Istituto Europeo di Oncologia	Milano
Italy	Ospedale Niguarda Cà Granda	Milano
Italy	Azienda Ospedaliera San Gerardo di Monza	Monza	Monza E Brianza
Italy	Arcispedale Santa Maria Nuova IRCCS	Reggio Emilia	Reggio Nella Emilia
Italy	Ospedale Civile SS Annunziata ASL 1	Sassari
Poland	Centrum Onkologii im. Prof. Franciszka Lukaszczyka w Bydgoszczy	Bydgoszcz
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk	Pomorskie
Poland	Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie, Spólka z o. o.	Kraków	Malopolskie
Poland	Olsztynski Osrodek Onkologiczny "Kopernik" sp. z o. o.	Olsztyn	Warminsko-Mazurskie
Poland	Centralny Szpital Kliniczny MSWiA	Warszawa
Poland	Centrum Onkologii - Instytut im Marii Sklodowskiej-Curie	Warszawa
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
Spain	Centro Oncológico Regional de Galicia	A Coruña	La Coruna
Spain	Hospital Nuestra Señora de Sonsoles	Avila
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Universitario de Girona Doctor Josep Trueta	Gerona
Spain	Centro Integral Oncológico Clara Campal, Hospital de Madrid Norte-San Chinarro	Madrid
Spain	Hospital Clinico Universitario San Carlos	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Instituto de Investigación Sanitaria	Madrid
Spain	Hospital Clinico Universitario de Valencia	Valencia
United States	Central Hematology Oncology Medical Group, Inc.	Alhambra	California
United States	Peachtree Hematology Oncology Consultants, PC	Atlanta	Georgia
United States	Comprehensive Blood and Cancer Center	Bakersfield	California
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Providence Saint Joseph Medical Center-Disney Family Cancer Center	Burbank	California
United States	Northwestern University	Chicago	Illinois
United States	Oncology Hematology Care, Inc.	Cincinnati	Ohio
United States	South Carolina Oncology Associates	Columbia	South Carolina
United States	Wilshire Oncology Medical Group, Inc.	Corona	California
United States	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas
United States	Virginal Cancer Specialists, PC	Fairfax	Virginia
United States	Center for Cancer and Blood Disorders, PC	Fort Worth	Texas
United States	Saint Jude Heritage Healthcare	Fullerton	California
United States	Florida Cancer Specialists	Gainesville	Florida
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Comprehensive Cancer Centers of Nevada	Henderson	Nevada
United States	Clearview Cancer Institute	Huntsville	Alabama
United States	Indiana University Simon Cancer Center	Indianapolis	Indiana
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	University of California San Diego Medical Center	La Jolla	California
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Suburban Hematology Oncology Associates, PC	Lawrenceville	Georgia
United States	Southeast Nebraska Cancer Center	Lincoln	Nebraska
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	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas
United States	University of Wisconsin	Madison	Wisconsin
United States	Signal Point Clinical Research Center, LLC	Middletown	Ohio
United States	Virginia Cancer Institute	Midlothian	Virginia
United States	Montana Cancer Institute	Missoula	Montana
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Yale University Smilow Cancer Hospital	New Haven	Connecticut
United States	New York University Clinical Cancer Center	New York	New York
United States	MD Anderson Cancer Center	Orlando	Florida
United States	Stanford University Medical Center	Palo Alto	California
United States	Wilshire Oncology Medical Group, Inc.	Pomona	California
United States	Kaiser Permanente Northwest Region Oncology Hematology	Portland	Oregon
United States	Cancer Care Associates Medical Group	Redondo Beach	California
United States	Pacific Shores Medical Group	Redondo Beach	California
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Intermountain Healthcare	Saint George	Utah
United States	Saint Joseph Oncology, Inc.	Saint Joseph	Missouri
United States	Florida Cancer Specialists	Saint Petersburg	Florida
United States	Utah Cancer Specialists	Salt Lake City	Utah
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	Seattle Cancer Care Alliance	Seattle	Washington
United States	Scott & White Memorial	Temple	Texas
United States	Hematology and Oncology Associates at BridgePoint	Tupelo	Mississippi
United States	Georgetown University	Washington	District of Columbia
United States	The Center for Cancer and Blood Disorders	Weatherford	Texas
United States	Oncology Hematology Care, Inc.	Wilmington	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  Poland,  Russian Federation,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Survival (OS)	The OS is measured as time from date of randomization to death regardless of cause. The OS was analyzed using KM estimates.	Randomization up to 33 months
Secondary	Objective Response Rate (ORR)	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.	Randomization up to 27 months