FOLFOX Plus SIR-SPHERES MICROSPHERES Versus FOLFOX Alone in Patients With Liver Mets From Primary Colorectal Cancer
SIRFLOX
Randomised Comparative Study Of Folfox6m Plus Sir-Spheres® Microspheres Versus Folfox6m Alone As First Line Treatment In Patients With Nonresectable Liver Metastases From Primary Colorectal Carcinoma
1 other identifier
interventional
530
11 countries
111
Brief Summary
This study is a randomized multi-center trial that will assess the effect of adding Selective Internal Radiation Therapy (SIRT), using SIR-Spheres microspheres®, to a standard chemotherapy regimen of FOLFOX as first line therapy in patients with non-resectable liver metastases from primary colorectal adenocarcinoma. Treatment with the biologic agent bevacizumab, if part of the standard of care at participating institutions, is allowed within this study at the discretion of the treating Investigator.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for not_applicable colorectal-cancer
Started Aug 2006
Longer than P75 for not_applicable colorectal-cancer
111 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
Study Start
First participant enrolled
August 1, 2006
CompletedFirst Submitted
Initial submission to the registry
July 25, 2008
CompletedFirst Posted
Study publicly available on registry
July 29, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2015
CompletedResults Posted
Study results publicly available
March 26, 2019
CompletedMarch 26, 2019
March 1, 2019
8.8 years
July 25, 2008
November 7, 2018
March 1, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-Free Survival (PFS) at Any Site
PFS defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as an increase in the sum of the longest diameters of ≥ 20% and an absolute increase in the sum of the longest diameters of ≥ 5 mm, or the appearance of a new lesion.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Secondary Outcomes (1)
Percentage of Participants With Overall Response
Through study completion, up to 60 months
Study Arms (2)
mFOLFOX6 + SIRT
EXPERIMENTALA single injection of SIR-Spheres microspheres into the liver plus systemic chemotherapy consisting of Oxaliplatin + Leucovorin + 5-Fluorouracil (FOLFOX)
mFOLFOX6
ACTIVE COMPARATORSystemic chemotherapy consisting of Oxaliplatin + Leucovorin + 5- Fluorouracil (FOLFOX).
Interventions
SIR-Spheres microspheres (yttrium-90 \[Y-90\] labelled resin microspheres), hepatic artery injection administered on Day 3 or 4 of cycle 1. mFOLFOX6 administered on Day 1 and at the start of each cycle every 14 days: 85 or 60 mg/m2 oxaliplatin by 2-hour intravenous (IV) infusion + 200 mg/m2 leucovorin by 2-hour IV infusion + 400 mg/m2 5-fluorouracil (5-FU) by IV bolus + 2.4 g/m2 5-FU by 46-hour continuous IV infusion. Treatment with the biologic agent bevacizumab, if part of standard practice at the participating institution, was permitted at the discretion of the treating Investigator. In the event that leucovorin was not available, use of levofolinic acid (the active S enantiomer) was acceptable at half the dose of the racemic leucovorin i.e. 100 mg/m2.
mFOLFOX6 administered on Day 1 and at the start of each cycle every 14 days: 85 or 60 mg/m2 oxaliplatin by 2-hour intravenous (IV) infusion + 200 mg/m2 leucovorin by 2-hour IV infusion + 400 mg/m2 5-fluorouracil (5-FU) by IV bolus + 2.4 g/m2 5-FU by 46-hour continuous IV infusion. Treatment with the biologic agent bevacizumab, if part of standard practice at the participating institution, was permitted at the discretion of the treating Investigator. In the event that leucovorin was not available, use of levofolinic acid (the active S enantiomer) was acceptable at half the dose of the racemic leucovorin i.e. 100 mg/m2.
Eligibility Criteria
You may qualify if:
- Unequivocal and measurable CT evidence of liver metastases which are not treatable by surgical resection or local ablation.
- Limited extra-hepatic metastases in the lung and/or lymph nodes are permitted (Lung: 5 lesions total, \< 1 cm, or 1 single lesion of up to 1.7 cm; Lymph nodules in one single anatomic area (pelvis, abdomen or chest): any number, \< 2 cm).
- Suitable for either treatment regimen.
- Prior chemotherapy for metastatic colorectal cancer is not allowed.
- WHO performance status 0-1.
- Adequate hematological, renal and hepatic function.
- Age 18 years or older.
- Willing and able to provide written informed consent.
- Life expectancy of at least 3 months without any active treatment.
You may not qualify if:
- Evidence of ascites, cirrhosis, portal hypertension, main portal or venous tumor involvement or thrombosis as determined by clinical or radiologic assessment.
- Previous radiotherapy delivered to the upper abdomen.
- Non-malignant disease that would render the patient unsuitable for treatment according to the protocol.
- Peripheral neuropathy \> grade 1 (NCI-CTC).
- Dose limiting toxicity with previous adjuvant 5-FU or oxaliplatin chemotherapy.
- Pregnant or breast-feeding.
- Other active malignancy.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Sirtex Medicallead
Study Sites (111)
Pinnacle Oncology Hematology
Scottsdale, Arizona, 85258, United States
City of Hope Hospital
Duarte, California, 91010, United States
Florida International University College of Medicine Practice
North Miami Beach, Florida, 33169, United States
Vanguard Health
Berwyn, Illinois, 60402, United States
University of Illinois at Chicago
Chicago, Illinois, 60612, United States
Ingalls Memorial Hospital
Harvey, Illinois, 80426, United States
Adventist Hinsdale Hospital
Hinsdale, Illinois, 60525, United States
University of Louisville
Louisville, Kentucky, 40202, United States
University of Maryland Medical Center
Baltimore, Maryland, 21201, United States
William Beaumont Hospital
Royal Oak, Michigan, 48073, United States
Virginia Piper Cancer Institute
Minneapolis, Minnesota, 55407, United States
Holy Name Hospital
Teaneck, New Jersey, 07666, United States
Montefiore Medical Center
The Bronx, New York, 10467, United States
Carolinas Hematology-Oncology Associates
Charlotte, North Carolina, 28203, United States
Carolinas Medical Center
Charlotte, North Carolina, 28203, United States
Altru Health Systems
Grand Forks, North Dakota, 58201, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15232, United States
St. Mark's Hospital
Salt Lake City, Utah, 84124, United States
University of Washington
Seattle, Washington, 98109, United States
Aurora St. Luke's Medical Center
Milwaukee, Wisconsin, 53215, United States
Medical College of Wisconsin/Froedtert Memorial Lutheran Hospital
Milwaukee, Wisconsin, 53226, United States
Concord Hospital
Concord, New South Wales, 2139, Australia
St. Vincent's Hospital
Darlinghurst, New South Wales, 2010, Australia
Nepean Cancer Care Centre
Kingswood, New South Wales, Australia
St. George Hospital
Kogarah, New South Wales, 2217, Australia
Royal North Shore Hospital
St Leonards, New South Wales, 2065, Australia
Sydney Adventist Hospital
Wahroonga, New South Wales, 2076, Australia
Westmead Hospital
Westmead, New South Wales, 2145, Australia
Wesley Medical Centre
Auchenflower, Queensland, 4066, Australia
Cairns Private Hospital
Cairns, Queensland, 4870, Australia
Royal Brisbane and Women's Hospital
Herston, Queensland, 4029, Australia
Gold Coast Health Service District
Southport, Queensland, 4215, Australia
HOCA Gold Coast Centre
Southport, Queensland, 4215, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia
Ashford Cancer Centre
Ashford, South Australia, Australia
Flinders Medical Centre
Bedford Park, South Australia, Australia
Lyell McEwin Hospital
Elizabeth Vale, South Australia, 5012, Australia
Queen Elizabeth II Hospital
Woodville South, South Australia, Australia
Royal Hobart Hospital
Hobart, Tasmania, 7000, Australia
Monash Medical Centre
Bentleigh East, Victoria, Australia
John Fawkner Private Hospital
Coburg, Victoria, 3058, Australia
Western Hospital
Footscray, Victoria, 3011, Australia
Peninsula Oncology Centre
Frankston, Victoria, 3199, Australia
South Eastern Private
Noble Park, Victoria, 3174, Australia
Royal Melbourne Hospital
Parkville, Victoria, 3050, Australia
Ringwood/Knox Private
Ringwood, Victoria, 3135, Australia
Maroondah Public
Ringwood East, Victoria, 3135, Australia
Hollywood Private Hospital
Nedlands, Western Australia, 6009, Australia
Sir Charles Gairdner Hospital
Nedlands, Western Australia, Australia
Mount Medical Centre
Perth, Western Australia, 6005, Australia
Royal Perth Hospital
Perth, Western Australia, Australia
OL Vrouw Ziekenhuis Aalst Gastro-Enterologie
Aalst, 9300, Belgium
ZNA Middelheim
Antwerp, 2020, Belgium
Antwerp University Hospital
Antwerp, Belgium
Imelda Ziekenhuis GI Clinical Research Centre
Bonheiden, 2820, Belgium
Sint-Josef Ziekenhuie (Campus Bornem)
Bornem, 2880, Belgium
Institut Jules Bordet - Centre de Tumeurs d'ULB
Brussels, Belgium
Universiteits Ziekenhuis Gent
Ghent, 9000, Belgium
AZ Maria Middelares
Ghent, Belgium
Hospital de Jolimont
Haine-Saint-Paul, 7100, Belgium
UZ Leuven, Campus Gasthuisberg
Leuven, 3000, Belgium
Centre Hospitalier Universitaire de Liege
Liège, Belgium
VZW Emmaus St. Maarten Ziekenhuis Mechelen and St. Marten Ziekenhuis Duffel
Mechelen, 2800, Belgium
AZ Heilige Familie
Reet, 2840, Belgium
Sint-Augustinus Ziekenhuis
Wilrijk, 2610, Belgium
CHU de Bordeau
Bordeaux, 33000, France
Hospitalier Universitaire de Grenoble C.H.U.
La Tronche, 38700, France
Centre Hospitalier General de Longjumeau
Longjumeau, 91161, France
Hopital de l'Archet II, CHU de Nice
Nice, 06202, France
Hospital European Georges Pompidou
Paris, 7590, France
Centre Eugene Marquis
Rennes, France
Internistische Gemeinschaftspraxis
Altstadt, 84028, Germany
Charite Campus Virchow Klinikum
Berlin, 1335, Germany
Braxiskooperation Bonn, Fachartze fur Innere Medizin
Bonn, 53123, Germany
Johanniterkrankenhaus Bonn
Bonn, Germany
Universitaetsklinikum Bonn
Bonn, Germany
Kliniken Essen Mitte
Essen, 45136, Germany
Gemeinschaftspraxis Hamatologie und internistische Onkologie
Essen, Germany
Universitat Frankfurt Institute fur Diagnostic und Interventionelle Radiologie
Frankfurt, 6059, Germany
Asklepios Klinik Altona, Abt. Radiologie, Neuroradiologie, Nuklearmedizin
Hamburg, 20367, Germany
Universitastsklinikum Saarland
Hamburg, Germany
Praxisgemeinschaft Dr. med. Peter Sandor und Peter Kohl
Holzkirch, 83607, Germany
Onklogische Praxis Dr. Gerald Gehbauer
Ingolstadt, 85049, Germany
Klinikum Karlsruhe, Stadtisches Klinikum Karlsruhe, Zentralinstitut fur Bildgebende Diagnostik
Karlsruhe, 76133, Germany
Schwerpunktpraxis fur Hamatologie und Onkologie
Magdeburg, 39104, Germany
Klinikum Magdeburg GmbH, Klinik für Hämatologie/Onkologie
Magdeburg, 39130, Germany
Universitaetsklinikum Magdeburg
Magdeburg, Germany
Universitatsklinikum GieBen und Marburg
Marburg, 35043, Germany
Hamato-Onkologische Schwerpunktspraxis
München, Germany
Klinikum Bogenhausen
München, Germany
Klinikum der Universitaet Muenchen
München, Germany
Klinikum rechts der Isar der TU Munchen
München, Germany
Schwerpunktspraxis fur Hamatologie und Internistische Onkologie
München, Germany
Praxis fur Hamatologie und Internnistische Onkologie
Velbert, 42551, Germany
Schwerpunktspraxis und Tagesklinik Dr. Perker/Dr. Sandherr
Weilheim, Germany
Rambam Medical Center
Haifa, Israel
Shaare-Zedek Medical Centre
Jerusalem, 91031, Israel
Rabin Medical Center, Beilinson Hospital
Petah Tikva, 49100, Israel
Sheba Medical Center
Ramat Gan, 52621, Israel
TA Sourasky Medical Center
Tel Aviv, 64239, Israel
A.O.U. die Bologna
Bologna, 40138, Italy
University of Auckland
Auckland, New Zealand
Christchurch Hospital
Christchurch, New Zealand
Dunedin Hospital
Dunedin, New Zealand
Wellington Hospital
Newtown, New Zealand
Palmerston North Hospital
Palmerston, New Zealand
Wojskowy Instytut Medyczny (WIM)
Warsaw, 04-141, Poland
Clinica Universitaria de Navarra
Pamplona, 31008, Spain
Hospital de Navarra, Servicio de Ongoligia, Planta Baja
Pamplona, 31008, Spain
Universitatsspital Zurich
Zurich, CH-8091, Switzerland
Related Publications (5)
van Hazel GA, Heinemann V, Sharma NK, Findlay MP, Ricke J, Peeters M, Perez D, Robinson BA, Strickland AH, Ferguson T, Rodriguez J, Kroning H, Wolf I, Ganju V, Walpole E, Boucher E, Tichler T, Shacham-Shmueli E, Powell A, Eliadis P, Isaacs R, Price D, Moeslein F, Taieb J, Bower G, Gebski V, Van Buskirk M, Cade DN, Thurston K, Gibbs P. SIRFLOX: Randomized Phase III Trial Comparing First-Line mFOLFOX6 (Plus or Minus Bevacizumab) Versus mFOLFOX6 (Plus or Minus Bevacizumab) Plus Selective Internal Radiation Therapy in Patients With Metastatic Colorectal Cancer. J Clin Oncol. 2016 May 20;34(15):1723-31. doi: 10.1200/JCO.2015.66.1181. Epub 2016 Feb 22.
PMID: 26903575RESULTWolstenholme J, Fusco F, Gray AM, Moschandreas J, Virdee PS, Love S, Van Hazel G, Gibbs P, Wasan HS, Sharma RA. Quality of life in the FOXFIRE, SIRFLOX and FOXFIRE-global randomised trials of selective internal radiotherapy for metastatic colorectal cancer. Int J Cancer. 2020 Aug 15;147(4):1078-1085. doi: 10.1002/ijc.32828. Epub 2020 Jan 9.
PMID: 31840815DERIVEDWasan HS, Gibbs P, Sharma NK, Taieb J, Heinemann V, Ricke J, Peeters M, Findlay M, Weaver A, Mills J, Wilson C, Adams R, Francis A, Moschandreas J, Virdee PS, Dutton P, Love S, Gebski V, Gray A; FOXFIRE trial investigators; SIRFLOX trial investigators; FOXFIRE-Global trial investigators; van Hazel G, Sharma RA. First-line selective internal radiotherapy plus chemotherapy versus chemotherapy alone in patients with liver metastases from colorectal cancer (FOXFIRE, SIRFLOX, and FOXFIRE-Global): a combined analysis of three multicentre, randomised, phase 3 trials. Lancet Oncol. 2017 Sep;18(9):1159-1171. doi: 10.1016/S1470-2045(17)30457-6. Epub 2017 Aug 3.
PMID: 28781171DERIVEDVirdee PS, Moschandreas J, Gebski V, Love SB, Francis EA, Wasan HS, van Hazel G, Gibbs P, Sharma RA. Protocol for Combined Analysis of FOXFIRE, SIRFLOX, and FOXFIRE-Global Randomized Phase III Trials of Chemotherapy +/- Selective Internal Radiation Therapy as First-Line Treatment for Patients With Metastatic Colorectal Cancer. JMIR Res Protoc. 2017 Mar 28;6(3):e43. doi: 10.2196/resprot.7201.
PMID: 28351831DERIVEDGibbs P, Gebski V, Van Buskirk M, Thurston K, Cade DN, Van Hazel GA; SIRFLOX Study Group. Selective Internal Radiation Therapy (SIRT) with yttrium-90 resin microspheres plus standard systemic chemotherapy regimen of FOLFOX versus FOLFOX alone as first-line treatment of non-resectable liver metastases from colorectal cancer: the SIRFLOX study. BMC Cancer. 2014 Dec 1;14:897. doi: 10.1186/1471-2407-14-897.
PMID: 25487708DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Janet Bell, M.B.A.
- Organization
- Sirtex Medical
Study Officials
- PRINCIPAL INVESTIGATOR
Peter Gibbs, MD
Melbourne Health
- PRINCIPAL INVESTIGATOR
Guy van Hazel, MD
Mount Medical Centre
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 25, 2008
First Posted
July 29, 2008
Study Start
August 1, 2006
Primary Completion
May 1, 2015
Study Completion
May 1, 2015
Last Updated
March 26, 2019
Results First Posted
March 26, 2019
Record last verified: 2019-03