FOLFOX6m Plus SIR-Spheres Microspheres vs FOLFOX6m Alone in Patients With Liver Mets From Primary Colorectal Cancer

NCT01721954 | Completed Phase 3 Results DMC

• 1 other identifier: STX0112
• Study Type: interventional
• Target: 209
• Locations: 13 countries
• Sites: 83

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.

Conditions

Colorectal Cancer Metastatic

Keywords

colon; rectum; metastatic colorectal cancer; liver metastases

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  OS defined as the time interval between the date of randomization and the date of death from any cause.

  From date of randomization until the date of death from any cause assessed up 3 yrs 8 months

Secondary Outcomes (1)

• Progression-free Survival

  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.

Study Arms (2)

Control Arm

ACTIVE COMPARATOR

Systemic chemotherapy with FOLFOX6m plus or minus bevacizumab repeated every two weeks until evidence of treatment failure.

Drug: FOLFOX6m

Experimental Arm

EXPERIMENTAL

Systemic chemotherapy with FOLFOX6m plus or minus bevacizumab plus SIR-Spheres microspheres.

Drug: FOLFOX6m; Device: SIR-Spheres microspheres

Interventions

FOLFOX6m DRUG

Control Arm; Experimental Arm

SIR-Spheres microspheres DEVICE

Experimental Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sirtex Medical: lead

Study Sites (83)

City of Hope

Duarte, California, 91010, United States

Location

Orlando Health

Orlando, Florida, 32806, United States

Location

Memorial Healthcare

Pembroke Pines, Florida, 33028, United States

Location

University of Illinois Chicago

Chicago, Illinois, 60607, United States

Location

Adventist Midwest Health

Hinsdale, Illinois, 60521, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Roswell Park Cancer Center

Buffalo, New York, 14263, United States

Location

Lenox Hill Hospital

New York, New York, 10075, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, 28203, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Spartanburg Regional Healthcare / Gibbs Cancer Center

Spartanburg, South Carolina, 29303, United States

Location

Methodist Hospital Dallas

Dallas, Texas, 75203, United States

Location

St. Mark's Hospital

Salt Lake City, Utah, 84124, United States

Location

Fletcher Allen Health Care

Burlington, Vermont, 05405, United States

Location

West Virginia University Healthcare

Morgantown, West Virginia, 26506, United States

Location

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, 53215, United States

Location

Border Medical Oncology Research Unit

Albury, New South Wales, 2640, Australia

Location

Gosford Hospital

Gosford, New South Wales, 2250, Australia

Location

Southern Medical Day Care Centre

Wollongong, New South Wales, 2500, Australia

Location

Royal Brisbane Hospital

Herston, Queensland, 4029, Australia

Location

Gold Coast Health Services District

Southport, Queensland, 4215, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Hobart Hospital

Hobart, Tasmania, 7000, Australia

Location

Monash Medical Centre

Bentleigh East, Victoria, 3165, Australia

Location

Box Hill Hospital

Box Hill, Victoria, 3128, Australia

Location

Western Hospital

Footscray, Victoria, 3011, Australia

Location

Peninsula Oncology Centre

Frankston, Victoria, 3199, Australia

Location

South Eastern Hospital

Noble Park, Victoria, 3174, Australia

Location

Maroondah Hospital

Ringwood East, Victoria, 3135, Australia

Location

St. John of God Murdoch Hospital

Murdoch, Western Australia, 6150, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

Location

OL Vrouw Ziekenhuis

Aalst, 9300, Belgium

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

University of Antwerp

Edegem, 2650, Belgium

Location

Universiteits Ziekenhuis Gent - Dienst Digestieve Oncologie

Ghent, 1K12IE, Belgium

Location

AZ Maria Middelaress

Ghent, 9000, Belgium

Location

CHU Sart Tilman

Liège, 4000, Belgium

Location

CHU Amiens

Amiens, 80054, France

Location

Centre Hospitalier General de Longjumeau

Clichy, 92118, France

Location

Hopital Beaujon

Clichy, 92118, France

Location

Hopital Albert Michallon - Grenoble

Grenoble, 38043, France

Location

Hopital Europeen Georges Pompidou

Paris, 75015, France

Location

CHU de Bordeaux - Hopital Saint Andre

Pessac, 33604, France

Location

CHU de Poitiers, Pole regional de cancerologie

Poitiers, 86021, France

Location

Centre Eugene Marquis

Rennes, 35042, France

Location

Vivantes Klinikum Neukolln Klinik fur Innere Medizin - Hamatologie und Onkologie

Berlin, 12351, Germany

Location

SLK-Kliniken Heilbronn GmbH, Klinik fur Radiologie

Heilbronn, 74078, Germany

Location

Stadtisches Klinikum Karlsruheg GMBH Klinik fur Nuklearmedizin

Karlsruhe, 76133, Germany

Location

Schwerpunktpraxix fur Hamatologie und Onkologie

Magdeburg, 39104, Germany

Location

Universitaetsklinikum Magdeburg, Klinik fur Radiologie und Nuklearmedizin

Magdeburg, 39120, Germany

Location

Klinikum Magdeburg GmbH, Klinik fur Allgemein und Viszeralchirurgie

Magdeburg, 39130, Germany

Location

Universitatsklinikum Marburg Klinik fur Hamatologie, Onkologie und Immunologie

Marburg, 35043, Germany

Location

Klinikum der Universitat Munchen

Munich, 81377, Germany

Location

Klinikum rechts der Isar der TU Munchen Medizinische Klinik II

München, 81675, Germany

Location

St. Franziskus Hospital Muenster

Münster, 48145, Germany

Location

Rambam Medical Center

Haifa, 31096, Israel

Location

Shaare-Zedek Medical Center

Jerusalem, 91031, Israel

Location

Hadassah Medical Center

Jerusalem, 91120, Israel

Location

TA Sourasky Medical Center, Oncology Department 6

Tel Aviv, 64239, Israel

Location

Sheba Medical Center - Governmental Hospital - Oncology Division

Tel Litwinsky, 56261, Israel

Location

Ospedale Regionale U. Parini

Aosta, 11100, Italy

Location

Dipartimento di Oncologia, Ospendali Riuniti di Bergamo

Bergamo, 24127, Italy

Location

A.O.U. die Bologna

Bologna, 40138, Italy

Location

Ufficio Sperimentale Cliniche, Oncologia Medica di Carle, Ospendale Santa Croce e Carle di Cuneo

Cuneo, 12100, Italy

Location

U.O. Oncologia Medica II, Nuovo Ospendale Santa Chiara, Azienda Ospendaliero Universitaria Pisana, Presidio Ospendaliero di Cisanello

Pisa, 56124, Italy

Location

Wellington Hospital

Newtown, Wellington Region, 6021, New Zealand

Location

Dunedin Hospital

Dunedin, 9016, New Zealand

Location

Auckland University

Grafton, 1023, New Zealand

Location

Regional Cancer Treatment Service

Palmerston North, 4414, New Zealand

Location

Instituto Portugues de Oncologia do Porto Francisco Gentil, E.P.E.

Porto, 4200-072, Portugal

Location

National Cancer Centre Singapore

Singapore, 169610, Singapore

Location

Seoul National University Hospital

Seoul, 110-744, South Korea

Location

Korea University Anam Hospital

Seoul, 136-705, South Korea

Location

Seoul St. Mary's Hospital

Seoul, 137-701, South Korea

Location

Hospital Universitario Puerta de Hierro Majadahonda

Madrid, 28222, Spain

Location

Clinica Universidad de Navarra

Pamplona, 31008, Spain

Location

Complejo Hospitalario de Navarra

Pamplona, 31008, Spain

Location

National Taiwan University Hospital

Taipei, 10048, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Related Publications (4)

• 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: 26903575 RESULT

• 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.

  PMID: 31840815 DERIVED

• 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.

  PMID: 28781171 DERIVED

• 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.

  PMID: 28351831 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Results Point of Contact

• Title: Janet Bell, M.B.A.
• Organization: Sirtex Medical

jbell@sirtex.com

+ 888-474-7839

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2012
• First Posted: November 6, 2012
• Study Start: May 1, 2013
• Primary Completion: December 23, 2016
• Study Completion: February 28, 2017
• Last Updated: November 5, 2019
• Results First Posted: October 22, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

KR (3); IT (5); TW (2); IL (5); DE (10); PT (1); SG (1); BE (6); ES (3); NZ (4); AU (17); FR (8); US (18)