Clinical trial NCT01483027: Efficacy Evaluation of TheraSphere Following Failed First Line Chemotherapy in Metastatic Colorectal Cancer
Official title: A Phase III Clinical Trial Evaluating TheraSphere® in Patients With Metastatic Colorectal Carcinoma of the Liver Who Have Failed First Line Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Colorectal Cancer Metastatic
Lead sponsor: Boston Scientific Corporation
Sponsor class: INDUSTRY
Collaborators: name: Biocompatibles UK Ltd
First posted: 2011-12-01
Enrollment: 428
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: The effectiveness and safety of TheraSphere will be evaluated in patients with colorectal cancer with metastases in the liver, who are scheduled to receive second line chemotherapy. All patients receive the standard of care chemotherapy with or without the addition of TheraSphere.


Eligibility criteria: Inclusion Criteria

* Must be male or female, 18 years of age or older, and of any ethnic or racial group
* If primary tumor has not been resected, it must be clinically stable
* Must have colorectal cancer with unresectable metastatic disease to the liver (unresectable unilobar or bilobar disease) who have disease progression in the liver with oxaliplatin or irinotecan based first line chemotherapy
* Must be eligible to receive second-line standard-of-care chemotherapy with either 1) an oxaliplatin-based chemotherapy regimen, or 2) an irinotecan-based chemotherapy regimen
* Must have baseline efficacy images with measurable target tumors in the liver according to RECIST 1.1 using standard imaging techniques taken within 28 days prior to randomization. Images must be taken after, or at the time of completion of first line chemotherapy
* Tumor replacement \<50% of total liver volume
* Current Eastern Cooperative Oncology Group (ECOG) of 0-1 through screening to first treatment on study
* Will have completed the first line chemotherapy regimen at least 14 days prior to initiation of 2nd line chemotherapy under the protocol
* Patient is willing to participate in the study and has signed the study informed consent
* Serum creatinine ≤ 2.0 mg/dL
* Serum bilirubin up to 1.2 x upper limit of normal
* Albumin ≥ 3.0 g/dL
* Must have neutrophil count \>1200/mm3 (1.2x109/L)

Exclusion Criteria

* History of hepatic encephalopathy
* Contraindications to angiography and selective visceral catheterization such as bleeding diathesis or coagulopathy that is not correctable by usual therapy of hemostatic agents (eg. closure device)
* History of severe peripheral allergy or intolerance to contrast agents, narcotics, sedatives or atropine that cannot be managed medically
* Presentation of pulmonary insufficiency or clinically evident chronic obstructive pulmonary disease
* Cirrhosis or portal hypertension
* Prior external beam radiation treatment to the liver
* Prior intra-arterial liver directed therapy, including transcatheter arterial chemoembolization (TACE) or Y-90 microsphere therapy
* Planned treatment with biological agents within 28 days prior to receiving TheraSphere
* Planned liver directed therapy or radiation therapy
* Intervention for, or compromise of, the Ampulla of Vater
* Clinically evident ascites (trace ascites on imaging is acceptable)
* Toxicities due to prior cancer therapy that have not resolved before the initiation of study treatment, if the Investigator determines that the continuing complication will compromise the safe treatment of the patient
* Significant life-threatening extra-hepatic disease, including patients who are on dialysis, have unresolved diarrhea, have serious unresolved infections including patients who are known to be human immunodeficiency virus (HIV) positive or have acute hepatitis B virus (HBV) or hepatitis C virus (HCV)
* confirmed extra-hepatic metastases. Limited indeterminate extra-hepatic lesions in the lung and/or lymph nodes are permitted (up to 5 lesions in the lung, with each individual lesion \<1 cm; any number of lymph nodes with each individual nodes \<1.5 cm)
* Contraindications to the planned second line standard-of-care chemotherapy regimen
* Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to randomization, and must not be breastfeeding and must agree to use contraceptive for duration of study.
* Participation in a clinical trial with an investigational therapy within 30 days prior to randomization
* Co-morbid disease or condition that would place the patient at undue risk and preclude safe use of TheraSphere treatment, in the Investigator's judgment

Primary outcomes:
measure: Progression Free Survival
timeFrame: From date of randomization until the date of first documented progression, as defined by RECIST 1:1 or date of death from any cause, whichever comes first, assessed up to a minimum of 1 year follow up or until study completion
measure: Hepatic Progression-Free Survival (HPFS)
timeFrame: Time from randomization until hepatic PD by BICR per RECIST 1.1 or death, whichever occurs first, assessed up to a minimum of 1 year follow up or study completion.
Secondary outcomes:
measure: Overall Survival
timeFrame: Time from date of randomization until date of death due to any cause; patients remaining on study post progression were followed until study completion; duration of follow up could be a few months to several years depending on when event was met.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: San Francisco
country: United States
facility: University of California San Fransico, Moffitt Hospital
state: California
city: Aurora
country: United States
facility: University of Colorado Denver Anschutz Medical Campus
state: Colorado
city: Newark
country: United States
facility: Christiana Care Hospital
state: Delaware
city: Boca Raton
country: United States
facility: Lynn Clinical Research Center, Boca Raton Regional Hospital
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine, Florida
state: Florida
city: Tampa
country: United States
facility: Moffit Cancer Center
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Urbana
country: United States
facility: Carle Clinic
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Farmington Hills
country: United States
facility: Wayne State Harper Hospita Karmanos Cancer Institute
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health
state: Michigan
city: Royal Oak
country: United States
facility: Beaumont Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Allina Health, Virginia Piper Cancer Institute
state: Minnesota
city: Minneapolis
country: United States
facility: Minneapolis
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Mallinckrodt Institute of Radiology
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University, Wexner Medical Center
state: Ohio
city: Dayton
country: United States
facility: Miami Valley Hospital
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Trevose
country: United States
facility: Aria Health
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: UT MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: St. Marks Hospital
state: Utah
city: Norfolk
country: United States
facility: Sentara Norfolk General
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: La Crosse
country: United States
facility: Gundersen Medical Foundation
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin/Froedtert Memorial Lutheran Hospital
state: Wisconsin
city: Wauwatosa
country: United States
facility: Aurora Research Institute
state: Wisconsin
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Aalst
country: Belgium
facility: Onze-Lieve-Vrouwziekenuis VZW Campus Aalst
city: Gent
country: Belgium
facility: AZ - Sint Lucas
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Halifax
country: Canada
facility: QEII Health Services Center, Halifax Infirmary Site
state: Nova Scotia
city: London
country: Canada
facility: London Regional Cancer program
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: University Health Network , Mount Sinai Hospital
state: Ontario
city: Montreal, Quebec
country: Canada
facility: McGill University Health Center - Glen Site
state: Quebec
city: Saskatoon
country: Canada
facility: Royal University Hospital
state: Saskatchewan
city: Hong Kong
country: China
facility: Hong Kong Sanatorium Hospital
city: Hong Kong
country: China
facility: Queen Mary Hospital
city: Montpellier
country: France
facility: CHRU Montpellier - Hopital St Eloi
state: Cedex 5
city: Angers
country: France
facility: CUH d'Angers
state: Cedex 9
city: Toulouse
country: France
facility: CHU Toulouse, Hôpital Rangueil
state: Cedex 9
city: Bordeaux
country: France
facility: Institut Bergognié
city: Clichy
country: France
facility: Hôpital Beaujon
city: Créteil
country: France
facility: Hôpital Henri Mondor
city: Dijon cedex
country: France
facility: Centre Georges Francois Leclerc
city: Lyon
country: France
facility: Centre Hospitalier Lyon-Sud
city: Marseille
country: France
facility: Hôpital La Timone
city: Nantes
country: France
facility: CHU Nantes-Hôtel Dieu
city: Nice
country: France
facility: CHU de Nice,, Hopital Archet 2 - Service d'Imagerie Médicale niveau -2
city: Pessac
country: France
facility: CHU Bordeaux
city: Poitiers
country: France
facility: Hôpital La Milétrie, CHU Poitiers, hépato gastroenterologie
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Bonn,
country: Germany
facility: Universitätsklinikum Bonn
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heilbronn
country: Germany
facility: SLK Kliniken, Heilbronn GmbH
city: Homburg
country: Germany
facility: Universitätsklinikum des Saarlandes
city: Leipzig
country: Germany
facility: University Hospital of Leipzig
city: Marburg
country: Germany
facility: Universitaetsklinikum Marburg Klinik für Dermatologie und Allergologie
city: Tübingen
country: Germany
facility: Eberhard-Karls-University Tübingen
city: Bologna
country: Italy
facility: Azienda Ospedaliera-Universitaria, Policlinico Sant'Orsola Malpighi
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: St. Mary's Hospital
city: Bialystok
country: Poland
facility: Białostockie Centrum Onkologii
city: Gliwice
country: Poland
facility: Centrum Onkologii - Instytut, im. Marii Skłodowskiej-Curie
city: Grudziądz
country: Poland
facility: Regionalny Szpital Specjalistyczny im. Dr Władysława Biegańskiego
city: Lublin
country: Poland
facility: Oddział Onkologii Klinicznej; Centrum Onkologii Ziemi Lubelskiej im. Św.Jana z Dukli.
city: Poznan
country: Poland
facility: Szpital Kliniczny im. Heliodora Święcickiego
city: Warszawa
country: Poland
facility: Centralny Szpital Kliniczny MSWiA
city: Warszawa
country: Poland
facility: Centrum Onkologii - Instytut
city: Warszawa
country: Poland
facility: Wojskowy Instytut Medyczny
city: Singapore
country: Singapore
facility: National University Hospital
city: Alcorcón
country: Spain
facility: Hospital Universitario Fundación Alcorcón
city: Barcelona,
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Coslada
country: Spain
facility: Hospital Universitario del Henares
city: Fuenlabrada
country: Spain
facility: Hospital Universitario de Fuenlabrada
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Málaga - Hospital General
city: Murcia,
country: Spain
facility: Hospital Universitario Virgen de la Arrixaca
city: Oviedo
country: Spain
facility: Avenida de Roma, s/n, Hospital Universitario Central de Asturias
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: Sabadell
country: Spain
facility: Parc Taulí Sabadell Hospital Universitari
city: Valencia
country: Spain
facility: Hospital Universitari i Politècnic La Fe
city: Zaragoza
country: Spain
facility: HCU Lozano Blesa, Planta 11-Oncología-Secretaría
city: Aberdeen
country: United Kingdom
facility: NHS Grampian - Aberdeen Royal Infirmary
city: Bath
country: United Kingdom
facility: Royal United Hospital Bath NHS Trust
city: Bebington
country: United Kingdom
facility: The Clatterbrdige Cancer Centre NHSF Trust
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital Cancer Centre
city: Bournemouth
country: United Kingdom
facility: The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust - Royal Bournemouth Hospital
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol NHS Foundation Trust - Bristol Haematology and Oncology Centre
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust - Addenbrookes Hospital
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: Glasgow,
country: United Kingdom
facility: Beatson Cancer Centre and University of Glasgow
city: Glasgow
country: United Kingdom
facility: University of Glasgow
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital
city: Huddersfield
country: United Kingdom
facility: Calderdale and Huddersfield NHS Foundation Trust - Huddersfield Royal Infirmary
city: Leeds
country: United Kingdom
facility: Leeds Hospitals NHS Trust
city: London
country: United Kingdom
facility: UCLH, University College London Hospitals
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Newcastle
country: United Kingdom
facility: The Newcastle upon Tyne Hospitals NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospital NHS Trust
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust Churchill Hospital
city: Romford
country: United Kingdom
facility: Barking, Havering and Redbridge University Hospitals NHS Trust - Queen's Hospital
city: Sheffield
country: United Kingdom
facility: Western Park Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
city: Swindon
country: United Kingdom
facility: Great Western Hospitals NHS Foundation Trust - The Great Western Hospital
city: Taunton
country: United Kingdom
facility: Taunton and Somerset NHS Foundation Trust - Musgrove Park Hospital
city: Walsall
country: United Kingdom
facility: Walsall Healthcare NHS Trust - Manor Hospital
city: Wolverhampton
country: United Kingdom
facility: The Royal Wolverhampton NHS Trust - New Cross Hospital
Study officials:
affiliation: Northwestern University
name: Mary F Mulcahy, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mulcahy MF, Mahvash A, Pracht M, Montazeri AH, Bandula S, Martin RCG 2nd, Herrmann K, Brown E, Zuckerman D, Wilson G, Kim TY, Weaver A, Ross P, Harris WP, Graham J, Mills J, Yubero Esteban A, Johnson MS, Sofocleous CT, Padia SA, Lewandowski RJ, Garin E, Sinclair P, Salem R; EPOCH Investigators. Radioembolization With Chemotherapy for Colorectal Liver Metastases: A Randomized, Open-Label, International, Multicenter, Phase III Trial. J Clin Oncol. 2021 Dec 10;39(35):3897-3907. doi: 10.1200/JCO.21.01839. Epub 2021 Sep 20.
citation: Chauhan N, Mulcahy MF, Salem R, Benson Iii AB, Boucher E, Bukovcan J, Cosgrove D, Laframboise C, Lewandowski RJ, Master F, El-Rayes B, Strosberg JR, Sze DY, Sharma RA. TheraSphere Yttrium-90 Glass Microspheres Combined With Chemotherapy Versus Chemotherapy Alone in Second-Line Treatment of Patients With Metastatic Colorectal Carcinoma of the Liver: Protocol for the EPOCH Phase 3 Randomized Clinical Trial. JMIR Res Protoc. 2019 Jan 17;8(1):e11545. doi: 10.2196/11545.