Clinical trial NCT00724503: FOLFOX Plus SIR-SPHERES MICROSPHERES Versus FOLFOX Alone in Patients With Liver Mets From Primary Colorectal Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Colorectal Cancer
Colorectal Carcinoma
Liver Metastases
Keywords: colon cancer
Colorectal carcinoma
liver metastases
SIR-Spheres microspheres
yttrium-90
FOLFOX
bevacizumab
metastatic colorectal cancer
Lead sponsor: Sirtex Medical
Sponsor class: INDUSTRY
First posted: 2008-07-29
Enrollment: 530
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: 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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria

* 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.
* Prior non-adjuvant chemotherapy for any malignancy. Adjuvant chemotherapy for colorectal cancer is not an exclusion criteria provided that it was completed more than 6 months before entry into the study.
* Pregnant or breast-feeding.
* Other active malignancy.

Primary outcomes:
measure: Progression-Free Survival (PFS) at Any Site
timeFrame: 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:
measure: Percentage of Participants With Overall Response
timeFrame: Through study completion, up to 60 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Pinnacle Oncology Hematology
state: Arizona
city: Duarte
country: United States
facility: City of Hope Hospital
state: California
city: North Miami Beach
country: United States
facility: Florida International University College of Medicine Practice
state: Florida
city: Berwyn
country: United States
facility: Vanguard Health
state: Illinois
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Harvey
country: United States
facility: Ingalls Memorial Hospital
state: Illinois
city: Hinsdale
country: United States
facility: Adventist Hinsdale Hospital
state: Illinois
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute
state: Minnesota
city: Teaneck
country: United States
facility: Holy Name Hospital
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Charlotte
country: United States
facility: Carolinas Hematology-Oncology Associates
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Grand Forks
country: United States
facility: Altru Health Systems
state: North Dakota
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Salt Lake City
country: United States
facility: St. Mark's Hospital
state: Utah
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Milwaukee
country: United States
facility: Aurora St. Luke's Medical Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin/Froedtert Memorial Lutheran Hospital
state: Wisconsin
city: Concord
country: Australia
facility: Concord Hospital
state: New South Wales
city: Darlinghurst
country: Australia
facility: St. Vincent's Hospital
state: New South Wales
city: Kingswood
country: Australia
facility: Nepean Cancer Care Centre
state: New South Wales
city: Kogarah
country: Australia
facility: St. George Hospital
state: New South Wales
city: St Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Wahroonga
country: Australia
facility: Sydney Adventist Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Auchenflower
country: Australia
facility: Wesley Medical Centre
state: Queensland
city: Cairns
country: Australia
facility: Cairns Private Hospital
state: Queensland
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Southport
country: Australia
facility: Gold Coast Health Service District
state: Queensland
city: Southport
country: Australia
facility: HOCA Gold Coast Centre
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Ashford
country: Australia
facility: Ashford Cancer Centre
state: South Australia
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Elizabeth Vale
country: Australia
facility: Lyell McEwin Hospital
state: South Australia
city: Woodville South
country: Australia
facility: Queen Elizabeth II Hospital
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Bentleigh East
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Coburg
country: Australia
facility: John Fawkner Private Hospital
state: Victoria
city: Footscray
country: Australia
facility: Western Hospital
state: Victoria
city: Frankston
country: Australia
facility: Peninsula Oncology Centre
state: Victoria
city: Noble Park
country: Australia
facility: South Eastern Private
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Ringwood East
country: Australia
facility: Maroondah Public
state: Victoria
city: Ringwood
country: Australia
facility: Ringwood/Knox Private
state: Victoria
city: Nedlands
country: Australia
facility: Hollywood Private Hospital
state: Western Australia
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Perth
country: Australia
facility: Mount Medical Centre
state: Western Australia
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Aalst
country: Belgium
facility: OL Vrouw Ziekenhuis Aalst Gastro-Enterologie
city: Antwerpen
country: Belgium
facility: ZNA Middelheim
city: Antwerp
country: Belgium
facility: Antwerp University Hospital
city: Bonheiden
country: Belgium
facility: Imelda Ziekenhuis GI Clinical Research Centre
city: Bornem
country: Belgium
facility: Sint-Josef Ziekenhuie (Campus Bornem)
city: Brussels
country: Belgium
facility: Institut Jules Bordet - Centre de Tumeurs d'ULB
city: Gent
country: Belgium
facility: Universiteits Ziekenhuis Gent
city: Gent
country: Belgium
facility: AZ Maria Middelares
city: Haine-Saint-Paul
country: Belgium
facility: Hospital de Jolimont
city: Leuven
country: Belgium
facility: UZ Leuven, Campus Gasthuisberg
city: Liege
country: Belgium
facility: Centre Hospitalier Universitaire de Liege
city: Mechelen
country: Belgium
facility: VZW Emmaus St. Maarten Ziekenhuis Mechelen and St. Marten Ziekenhuis Duffel
city: Reet
country: Belgium
facility: AZ Heilige Familie
city: Wilrijk
country: Belgium
facility: Sint-Augustinus Ziekenhuis
city: Bordeaux
country: France
facility: CHU de Bordeau
city: La Tronche
country: France
facility: Hospitalier Universitaire de Grenoble C.H.U.
city: Longjumeau
country: France
facility: Centre Hospitalier General de Longjumeau
city: Nice
country: France
facility: Hopital de l'Archet II, CHU de Nice
city: Paris
country: France
facility: Hospital European Georges Pompidou
city: Rennes Cedex
country: France
facility: Centre Eugene Marquis
city: Altstadt
country: Germany
facility: Internistische Gemeinschaftspraxis
city: Berlin
country: Germany
facility: Charite Campus Virchow Klinikum
city: Bonn
country: Germany
facility: Braxiskooperation Bonn, Fachartze fur Innere Medizin
city: Bonn
country: Germany
facility: Johanniterkrankenhaus Bonn
city: Bonn
country: Germany
facility: Universitaetsklinikum Bonn
city: Essen
country: Germany
facility: Kliniken Essen Mitte
city: Essen
country: Germany
facility: Gemeinschaftspraxis Hamatologie und internistische Onkologie
city: Frankfurt
country: Germany
facility: Universitat Frankfurt Institute fur Diagnostic und Interventionelle Radiologie
city: Hamburg
country: Germany
facility: Asklepios Klinik Altona, Abt. Radiologie, Neuroradiologie, Nuklearmedizin
city: Hamburg
country: Germany
facility: Universitastsklinikum Saarland
city: Holzkirch
country: Germany
facility: Praxisgemeinschaft Dr. med. Peter Sandor und Peter Kohl
city: Ingolstadt
country: Germany
facility: Onklogische Praxis Dr. Gerald Gehbauer
city: Karlsruhe
country: Germany
facility: Klinikum Karlsruhe, Stadtisches Klinikum Karlsruhe, Zentralinstitut fur Bildgebende Diagnostik
city: Magdeburg
country: Germany
facility: Schwerpunktpraxis fur Hamatologie und Onkologie
city: Magdeburg
country: Germany
facility: Klinikum Magdeburg GmbH, Klinik für Hämatologie/Onkologie
city: Magdeburg
country: Germany
facility: Universitaetsklinikum Magdeburg
city: Marburg
country: Germany
facility: Universitatsklinikum GieBen und Marburg
city: Muenchen
country: Germany
facility: Klinikum Bogenhausen
city: Muenchen
country: Germany
facility: Klinikum der Universitaet Muenchen
city: Munchen
country: Germany
facility: Hamato-Onkologische Schwerpunktspraxis
city: Munchen
country: Germany
facility: Klinikum rechts der Isar der TU Munchen
city: Munchen
country: Germany
facility: Schwerpunktspraxis fur Hamatologie und Internistische Onkologie
city: Velbert
country: Germany
facility: Praxis fur Hamatologie und Internnistische Onkologie
city: Weilheim
country: Germany
facility: Schwerpunktspraxis und Tagesklinik Dr. Perker/Dr. Sandherr
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Shaare-Zedek Medical Centre
city: Petah Tiqva
country: Israel
facility: Rabin Medical Center, Beilinson Hospital
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Tel Aviv
country: Israel
facility: TA Sourasky Medical Center
city: Bologna
country: Italy
facility: A.O.U. die Bologna
city: Auckland
country: New Zealand
facility: University of Auckland
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Dunedin
country: New Zealand
facility: Dunedin Hospital
city: Newtown
country: New Zealand
facility: Wellington Hospital
city: Palmerston
country: New Zealand
facility: Palmerston North Hospital
city: Warsaw
country: Poland
facility: Wojskowy Instytut Medyczny (WIM)
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
city: Pamplona
country: Spain
facility: Hospital de Navarra, Servicio de Ongoligia, Planta Baja
city: Zurich
country: Switzerland
facility: Universitatsspital Zurich
Study officials:
affiliation: Melbourne Health
name: Peter Gibbs, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mount Medical Centre
name: Guy van Hazel, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Wolstenholme 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.
citation: Wasan 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.
citation: Virdee 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.
citation: Gibbs 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.