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

Colorectal Cancer Clinical Trial

— SIRFLOX  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00724503
• Other study ID #: STX0206
• Status: Completed
• Phase: N/A
• Start date: August 2006
• Est. completion date: May 2015

Study information

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

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 530
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Colorectal Cancer
• Colorectal Carcinoma
• Colorectal Neoplasms
• Liver Metastases
• Liver Neoplasms
• Neoplasm Metastasis

Intervention

Device:
• 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.

Drug:
• 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.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Ashford Cancer Centre	Ashford	South Australia
Australia	Wesley Medical Centre	Auchenflower	Queensland
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Monash Medical Centre	Bentleigh East	Victoria
Australia	Cairns Private Hospital	Cairns	Queensland
Australia	John Fawkner Private Hospital	Coburg	Victoria
Australia	Concord Hospital	Concord	New South Wales
Australia	St. Vincent's Hospital	Darlinghurst	New South Wales
Australia	Lyell McEwin Hospital	Elizabeth Vale	South Australia
Australia	Western Hospital	Footscray	Victoria
Australia	Peninsula Oncology Centre	Frankston	Victoria
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Nepean Cancer Care Centre	Kingswood	New South Wales
Australia	St. George Hospital	Kogarah	New South Wales
Australia	Hollywood Private Hospital	Nedlands	Western Australia
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Australia	South Eastern Private	Noble Park	Victoria
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Mount Medical Centre	Perth	Western Australia
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Ringwood/Knox Private	Ringwood	Victoria
Australia	Maroondah Public	Ringwood East	Victoria
Australia	Gold Coast Health Service District	Southport	Queensland
Australia	HOCA Gold Coast Centre	Southport	Queensland
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	Queen Elizabeth II Hospital	Woodville South	South Australia
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Belgium	OL Vrouw Ziekenhuis Aalst Gastro-Enterologie	Aalst
Belgium	Antwerp University Hospital	Antwerp
Belgium	ZNA Middelheim	Antwerpen
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	AZ Maria Middelares	Gent
Belgium	Universiteits Ziekenhuis Gent	Gent
Belgium	Hospital de Jolimont	Haine-Saint-Paul
Belgium	UZ Leuven, Campus Gasthuisberg	Leuven
Belgium	Centre Hospitalier Universitaire de Liege	Liege
Belgium	VZW Emmaus St. Maarten Ziekenhuis Mechelen and St. Marten Ziekenhuis Duffel	Mechelen
Belgium	AZ Heilige Familie	Reet
Belgium	Sint-Augustinus Ziekenhuis	Wilrijk
France	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 Cedex
Germany	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	Gemeinschaftspraxis Hamatologie und internistische Onkologie	Essen
Germany	Kliniken Essen Mitte	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	Klinikum Magdeburg GmbH, Klinik für Hämatologie/Onkologie	Magdeburg
Germany	Schwerpunktpraxis fur Hamatologie und Onkologie	Magdeburg
Germany	Universitaetsklinikum Magdeburg	Magdeburg
Germany	Universitatsklinikum GieBen und Marburg	Marburg
Germany	Klinikum Bogenhausen	Muenchen
Germany	Klinikum der Universitaet Muenchen	Muenchen
Germany	Hamato-Onkologische Schwerpunktspraxis	Munchen
Germany	Klinikum rechts der Isar der TU Munchen	Munchen
Germany	Schwerpunktspraxis fur Hamatologie und Internistische Onkologie	Munchen
Germany	Praxis fur Hamatologie und Internnistische Onkologie	Velbert
Germany	Schwerpunktspraxis und Tagesklinik Dr. Perker/Dr. Sandherr	Weilheim
Israel	Rambam Medical Center	Haifa
Israel	Shaare-Zedek Medical Centre	Jerusalem
Israel	Rabin Medical Center, Beilinson Hospital	Petah Tiqva
Israel	Sheba Medical Center	Ramat Gan
Israel	TA Sourasky Medical Center	Tel Aviv
Italy	A.O.U. die Bologna	Bologna
New Zealand	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
Poland	Wojskowy Instytut Medyczny (WIM)	Warsaw
Spain	Clinica Universitaria de Navarra	Pamplona
Spain	Hospital de Navarra, Servicio de Ongoligia, Planta Baja	Pamplona
Switzerland	Universitatsspital Zurich	Zurich
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Vanguard Health	Berwyn	Illinois
United States	Montefiore Medical Center	Bronx	New York
United States	Carolinas Hematology-Oncology Associates	Charlotte	North Carolina
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	University of Illinois at Chicago	Chicago	Illinois
United States	City of Hope Hospital	Duarte	California
United States	Altru Health Systems	Grand Forks	North Dakota
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Adventist Hinsdale Hospital	Hinsdale	Illinois
United States	University of Louisville	Louisville	Kentucky
United States	Aurora St. Luke's Medical Center	Milwaukee	Wisconsin
United States	Medical College of Wisconsin/Froedtert Memorial Lutheran Hospital	Milwaukee	Wisconsin
United States	Virginia Piper Cancer Institute	Minneapolis	Minnesota
United States	Florida International University College of Medicine Practice	North Miami Beach	Florida
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	William Beaumont Hospital	Royal Oak	Michigan
United States	St. Mark's Hospital	Salt Lake City	Utah
United States	Pinnacle Oncology Hematology	Scottsdale	Arizona
United States	University of Washington	Seattle	Washington
United States	Holy Name Hospital	Teaneck	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Sirtex Medical

Countries where clinical trial is conducted

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

References & Publications (1)

van Hazel GA, Heinemann V, Sharma NK, Findlay MP, Ricke J, Peeters M, Perez D, Robinson BA, Strickland AH, Ferguson T, Rodríguez J, Kröning H, Wolf I, Ganju V, Walpole E, Boucher E, Tichler T, Shacham-Shmueli E, Powell A, Eliadis P, Isaacs R, Price D, Moe — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Percentage of Participants With Overall Response	Tumour Response Rate per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT: Complete Response (CR) - Disappearance of all target lesions which is confirmed if determined by two observations not less than 4 weeks apart; Partial Response (PR) - >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	Through study completion, up to 60 months