FOLFOX Plus SIR-SPHERES MICROSPHERES Versus FOLFOX Alone in Patients With Liver Mets From Primary Colorectal Cancer

NCT ID: NCT00724503

Last Updated: 2019-03-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 530 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-08-31
• Study Completion Date: 2015-05-31

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.

Conditions

Colorectal Cancer; Colorectal Carcinoma; Liver Metastases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

mFOLFOX6 + SIRT

A single injection of SIR-Spheres microspheres into the liver plus systemic chemotherapy consisting of Oxaliplatin + Leucovorin + 5-Fluorouracil (FOLFOX)

Group Type: EXPERIMENTAL

SIR-Spheres yttrium-90 microspheres

Intervention Type: DEVICE

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

Systemic chemotherapy consisting of Oxaliplatin + Leucovorin + 5- Fluorouracil (FOLFOX).

Group Type: ACTIVE_COMPARATOR

Systemic chemotherapy (FOLFOX)

Intervention Type: DRUG

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.

Interventions

SIR-Spheres yttrium-90 microspheres

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.

Intervention Type: DEVICE

Systemic chemotherapy (FOLFOX)

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.

Intervention Type: DRUG

Other Intervention Names

mFOLFOX6m + SIRT; SIR-Spheres Y-90 microspheres; mFOLFOX6

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.
• Pregnant or breast-feeding.
• Other active malignancy.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sirtex Medical

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter Gibbs, MD

Role: PRINCIPAL_INVESTIGATOR

Melbourne Health

Guy van Hazel, MD

Role: PRINCIPAL_INVESTIGATOR

Mount Medical Centre

Locations

Schwerpunktspraxis fur Hamatologie und Internistische Onkologie

München, , Germany

Praxis fur Hamatologie und Internnistische Onkologie

Velbert, , Germany

Schwerpunktspraxis und Tagesklinik Dr. Perker/Dr. Sandherr

Weilheim, , Germany

Rambam Medical Center

Haifa, , Israel

Shaare-Zedek Medical Centre

Jerusalem, , Israel

Rabin Medical Center, Beilinson Hospital

Petah Tikva, , Israel

Sheba Medical Center

Ramat Gan, , Israel

TA Sourasky Medical Center

Tel Aviv, , Israel

A.O.U. die Bologna

Bologna, , 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, , Poland

Clinica Universitaria de Navarra

Pamplona, , Spain

Hospital de Navarra, Servicio de Ongoligia, Planta Baja

Pamplona, , Spain

Universitatsspital Zurich

Zurich, , Switzerland

Pinnacle Oncology Hematology

Scottsdale, Arizona, United States

City of Hope Hospital

Duarte, California, United States

Florida International University College of Medicine Practice

North Miami Beach, Florida, United States

Vanguard Health

Berwyn, Illinois, United States

University of Illinois at Chicago

Chicago, Illinois, United States

Ingalls Memorial Hospital

Harvey, Illinois, United States

Adventist Hinsdale Hospital

Hinsdale, Illinois, United States

University of Louisville

Louisville, Kentucky, United States

University of Maryland Medical Center

Baltimore, Maryland, United States

William Beaumont Hospital

Royal Oak, Michigan, United States

Virginia Piper Cancer Institute

Minneapolis, Minnesota, United States

Holy Name Hospital

Teaneck, New Jersey, United States

Montefiore Medical Center

The Bronx, New York, United States

Carolinas Hematology-Oncology Associates

Charlotte, North Carolina, United States

Carolinas Medical Center

Charlotte, North Carolina, United States

Altru Health Systems

Grand Forks, North Dakota, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

St. Mark's Hospital

Salt Lake City, Utah, United States

University of Washington

Seattle, Washington, United States

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, United States

Medical College of Wisconsin/Froedtert Memorial Lutheran Hospital

Milwaukee, Wisconsin, United States

Concord Hospital

Concord, New South Wales, Australia

St. Vincent's Hospital

Darlinghurst, New South Wales, Australia

Nepean Cancer Care Centre

Kingswood, New South Wales, Australia

St. George Hospital

Kogarah, New South Wales, Australia

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Sydney Adventist Hospital

Wahroonga, New South Wales, Australia

Westmead Hospital

Westmead, New South Wales, Australia

Wesley Medical Centre

Auchenflower, Queensland, Australia

Cairns Private Hospital

Cairns, Queensland, Australia

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Gold Coast Health Service District

Southport, Queensland, Australia

HOCA Gold Coast Centre

Southport, Queensland, 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, Australia

Queen Elizabeth II Hospital

Woodville South, South Australia, Australia

Royal Hobart Hospital

Hobart, Tasmania, Australia

Monash Medical Centre

Bentleigh East, Victoria, Australia

John Fawkner Private Hospital

Coburg, Victoria, Australia

Western Hospital

Footscray, Victoria, Australia

Peninsula Oncology Centre

Frankston, Victoria, Australia

South Eastern Private

Noble Park, Victoria, Australia

Royal Melbourne Hospital

Parkville, Victoria, Australia

Ringwood/Knox Private

Ringwood, Victoria, Australia

Maroondah Public

Ringwood East, Victoria, Australia

Hollywood Private Hospital

Nedlands, Western Australia, Australia

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Mount Medical Centre

Perth, Western Australia, Australia

Royal Perth Hospital

Perth, Western Australia, Australia

OL Vrouw Ziekenhuis Aalst Gastro-Enterologie

Aalst, , Belgium

ZNA Middelheim

Antwerp, , Belgium

Antwerp University Hospital

Antwerp, , Belgium

Imelda Ziekenhuis GI Clinical Research Centre

Bonheiden, , Belgium

Sint-Josef Ziekenhuie (Campus Bornem)

Bornem, , Belgium

Institut Jules Bordet - Centre de Tumeurs d'ULB

Brussels, , Belgium

Universiteits Ziekenhuis Gent

Ghent, , Belgium

AZ Maria Middelares

Ghent, , Belgium

Hospital de Jolimont

Haine-Saint-Paul, , Belgium

UZ Leuven, Campus Gasthuisberg

Leuven, , Belgium

Centre Hospitalier Universitaire de Liege

Liège, , Belgium

VZW Emmaus St. Maarten Ziekenhuis Mechelen and St. Marten Ziekenhuis Duffel

Mechelen, , Belgium

AZ Heilige Familie

Reet, , Belgium

Sint-Augustinus Ziekenhuis

Wilrijk, , Belgium

CHU de Bordeau

Bordeaux, , France

Hospitalier Universitaire de Grenoble C.H.U.

La Tronche, , France

Centre Hospitalier General de Longjumeau

Longjumeau, , France

Hopital de l'Archet II, CHU de Nice

Nice, , France

Hospital European Georges Pompidou

Paris, , France

Centre Eugene Marquis

Rennes, , France

Internistische Gemeinschaftspraxis

Altstadt, , Germany

Charite Campus Virchow Klinikum

Berlin, , Germany

Braxiskooperation Bonn, Fachartze fur Innere Medizin

Bonn, , Germany

Johanniterkrankenhaus Bonn

Bonn, , Germany

Universitaetsklinikum Bonn

Bonn, , Germany

Kliniken Essen Mitte

Essen, , Germany

Gemeinschaftspraxis Hamatologie und internistische Onkologie

Essen, , Germany

Universitat Frankfurt Institute fur Diagnostic und Interventionelle Radiologie

Frankfurt, , Germany

Asklepios Klinik Altona, Abt. Radiologie, Neuroradiologie, Nuklearmedizin

Hamburg, , Germany

Universitastsklinikum Saarland

Hamburg, , Germany

Praxisgemeinschaft Dr. med. Peter Sandor und Peter Kohl

Holzkirch, , Germany

Onklogische Praxis Dr. Gerald Gehbauer

Ingolstadt, , Germany

Klinikum Karlsruhe, Stadtisches Klinikum Karlsruhe, Zentralinstitut fur Bildgebende Diagnostik

Karlsruhe, , Germany

Schwerpunktpraxis fur Hamatologie und Onkologie

Magdeburg, , Germany

Klinikum Magdeburg GmbH, Klinik für Hämatologie/Onkologie

Magdeburg, , Germany

Universitaetsklinikum Magdeburg

Magdeburg, , Germany

Universitatsklinikum GieBen und Marburg

Marburg, , 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

Countries

United States; Australia; Belgium; France; Germany; Israel; Italy; New Zealand; Poland; Spain; Switzerland

References

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.

Reference Type: RESULT

PMID: 26903575 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31840815 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28781171 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28351831 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25487708 (View on PubMed)

Other Identifiers

STX0206

Identifier Type: -

Identifier Source: org_study_id