Clinical trial NCT01721954: FOLFOX6m Plus SIR-Spheres Microspheres vs FOLFOX6m Alone in Patients With Liver Mets From Primary Colorectal Cancer
Official title: Assessment of Overall Survival of FOLFOX6m Plus SIR-Spheres Microspheres Versus FOLFOX6m Alone as First-line Treatment in Patients With Non-resectable Liver Metastases From Primary Colorectal Carcinoma in a Randomised Clinical Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colorectal Cancer Metastatic
Keywords: colon
rectum
metastatic colorectal cancer
liver metastases
Lead sponsor: Sirtex Medical
Sponsor class: INDUSTRY
First posted: 2012-11-06
Enrollment: 209
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 study that will compare the efficacy and safety of selective internal radiation therapy (SIRT) using SIR-Spheres microspheres plus a standard chemotherapy regimen of FOLFOX6m versus FOLFOX6m alone as first-line therapy in patients with non-resectable liver metastases from primary colorectal carcinoma.

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 Investigator.


Eligibility criteria: Inclusion Criteria:

* Age 18 years or older
* Willing and able to provide written informed consent
* 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)
* All imaging evidence used as part of the screening process must be within 28 days
* Suitable for either treatment regimen
* WHO performance status 0-1
* Adequate hematological, renal and hepatic function
* Life expectancy of at least 3 months without any active treatment

Exclusion Criteria:

* Evidence of ascites, cirrhosis, portal hypertension, main portal or venous involvement or thrombosis as determined by clinical or radiologic assessment
* Previous radiotherapy delivered to the liver
* Non-malignant disease that would render the patient unsuitable for treatment according to the protocol
* Peripheral neuropathy \> grade 2 (NCI-CTC)
* Dose-limiting toxicity associated with previous adjuvant 5-FU or oxaliplatin chemotherapy
* Prior non-adjuvant chemotherapy for any malignancy. Adjuvant chemotherapy for colorectal cancer is permitted provided that it was completed more than 6 months before entry into the study
* Pregnant or breast feeding
* Concurrent or prior history of cancer other than adequately treated non-melanoma skin cancer or carcinoma in situ of the cervix
* Allergy to contrast media that would preclude angiography of the hepatic arteries

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: From date of randomization until the date of death from any cause assessed up 3 yrs 8 months
Secondary outcomes:
measure: Progression-free Survival
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 3 years 8 months.
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Orlando
country: United States
facility: Orlando Health
state: Florida
city: Pembroke Pines
country: United States
facility: Memorial Healthcare
state: Florida
city: Chicago
country: United States
facility: University of Illinois Chicago
state: Illinois
city: Hinsdale
country: United States
facility: Adventist Midwest Health
state: Illinois
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Center
state: New York
city: New York
country: United States
facility: Lenox Hill Hospital
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Spartanburg
country: United States
facility: Spartanburg Regional Healthcare / Gibbs Cancer Center
state: South Carolina
city: Dallas
country: United States
facility: Methodist Hospital Dallas
state: Texas
city: Salt Lake City
country: United States
facility: St. Mark's Hospital
state: Utah
city: Burlington
country: United States
facility: Fletcher Allen Health Care
state: Vermont
city: Morgantown
country: United States
facility: West Virginia University Healthcare
state: West Virginia
city: Milwaukee
country: United States
facility: Aurora St. Luke's Medical Center
state: Wisconsin
city: Albury
country: Australia
facility: Border Medical Oncology Research Unit
state: New South Wales
city: Gosford
country: Australia
facility: Gosford Hospital
state: New South Wales
city: Wollongong
country: Australia
facility: Southern Medical Day Care Centre
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane Hospital
state: Queensland
city: Southport
country: Australia
facility: Gold Coast Health Services District
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Hobart
country: Australia
facility: Hobart Hospital
state: Tasmania
city: Bentleigh East
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Box Hill
country: Australia
facility: Box Hill 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 Hospital
state: Victoria
city: Ringwood East
country: Australia
facility: Maroondah Hospital
state: Victoria
city: Murdoch
country: Australia
facility: St. John of God Murdoch Hospital
state: Western Australia
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Aalst
country: Belgium
facility: OL Vrouw Ziekenhuis
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Edegem
country: Belgium
facility: University of Antwerp
city: Gent
country: Belgium
facility: Universiteits Ziekenhuis Gent - Dienst Digestieve Oncologie
city: Gent
country: Belgium
facility: AZ Maria Middelaress
city: Liege
country: Belgium
facility: CHU Sart Tilman
city: Amiens Cedex 1
country: France
facility: CHU Amiens
city: Clichy Cedex
country: France
facility: Centre Hospitalier General de Longjumeau
city: Clichy Cedex
country: France
facility: Hopital Beaujon
city: Grenoble Cedex 9
country: France
facility: Hopital Albert Michallon - Grenoble
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou
city: Pessac
country: France
facility: CHU de Bordeaux - Hopital Saint Andre
city: Poitiers cedex
country: France
facility: CHU de Poitiers, Pole regional de cancerologie
city: Rennes Cedex
country: France
facility: Centre Eugene Marquis
city: Berlin
country: Germany
facility: Vivantes Klinikum Neukolln Klinik fur Innere Medizin - Hamatologie und Onkologie
city: Heilbronn
country: Germany
facility: SLK-Kliniken Heilbronn GmbH, Klinik fur Radiologie
city: Karlsruhe
country: Germany
facility: Stadtisches Klinikum Karlsruheg GMBH Klinik fur Nuklearmedizin
city: Magdeburg
country: Germany
facility: Schwerpunktpraxix fur Hamatologie und Onkologie
city: Magdeburg
country: Germany
facility: Universitaetsklinikum Magdeburg, Klinik fur Radiologie und Nuklearmedizin
city: Magdeburg
country: Germany
facility: Klinikum Magdeburg GmbH, Klinik fur Allgemein und Viszeralchirurgie
city: Marburg
country: Germany
facility: Universitatsklinikum Marburg Klinik fur Hamatologie, Onkologie und Immunologie
city: Muenster
country: Germany
facility: St. Franziskus Hospital Muenster
city: Munchen
country: Germany
facility: Klinikum rechts der Isar der TU Munchen Medizinische Klinik II
city: Munich
country: Germany
facility: Klinikum der Universitat Munchen
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Shaare-Zedek Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Tel Aviv
country: Israel
facility: TA Sourasky Medical Center, Oncology Department 6
city: Tel Hashomer
country: Israel
facility: Sheba Medical Center - Governmental Hospital - Oncology Division
city: Aosta
country: Italy
facility: Ospedale Regionale U. Parini
city: Bergamo
country: Italy
facility: Dipartimento di Oncologia, Ospendali Riuniti di Bergamo
city: Bologna
country: Italy
facility: A.O.U. die Bologna
city: Cuneo
country: Italy
facility: Ufficio Sperimentale Cliniche, Oncologia Medica di Carle, Ospendale Santa Croce e Carle di Cuneo
city: Pisa
country: Italy
facility: U.O. Oncologia Medica II, Nuovo Ospendale Santa Chiara, Azienda Ospendaliero Universitaria Pisana, Presidio Ospendaliero di Cisanello
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul St. Mary's Hospital
city: Newtown
country: New Zealand
facility: Wellington Hospital
state: Wellington
city: Dunedin
country: New Zealand
facility: Dunedin Hospital
city: Grafton
country: New Zealand
facility: Auckland University
city: Palmerston North
country: New Zealand
facility: Regional Cancer Treatment Service
city: Porto
country: Portugal
facility: Instituto Portugues de Oncologia do Porto Francisco Gentil, E.P.E.
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
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.