Clinical trial NCT01767857: A Phase III Study of Xilonix in Patients With Advanced Colorectal Cancer
Official title: Phase III Double-blinded, Placebo Controlled Study of Xilonix™ for Improving Survival in Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Metastatic Colorectal Cancer
Keywords: Pivotal
Colorectal
Survival
Phase 3
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2013-01-14
Enrollment: 643
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 purpose of this study is to determine if the True Human Monoclonal antibody Xilonix (MABp1) can prolong the life of colorectal carcinoma patients that are refractory to standard therapy.

Detailed description: In the setting of refractory, metastatic disease a complete resolution of tumor burden is not a reasonable expectation. Instead, the primary goal of anti-tumor therapy at this stage is to eliminate or reduce the symptomatic effects of the tumor, while trying to prolong survival for as long as possible. Due to treatment related morbidity however, few treatment modalities are ideal for this objective. Even with the most recent targeted agents (such as multi-kinase inhibitors), drug related toxicities frequently lead to relatively short treatment durations. With discontinuation of therapy, disease progression is uncontrolled and prognosis is poor.

New agents that control disease progression-while improving tumor-related symptoms, rather than causing significant therapy related morbidity-are vitally needed to treat patients with advanced cancer, including those with colorectal cancer. An approach has been taken to develop such an agent using a monoclonal antibody to block the chronic inflammation involved in both malignant disease progression and constitutional symptoms.

Xilonix™ is expected to inhibit tumor growth and metastasis by interrupting crucial signals that drive angiogenesis and invasiveness. The antibody therapy may also block tumor microenvironment infiltration by leukocytes (such as myeloid suppressor cells) that suppress antitumor immunity, enabling better host immune control of the disease. In addition to local effects on the tumor, Xilonix™ is expected to work systemically to correct the metabolic dysregulation, fatigue and anxiety mediated by chronic inflammatory signaling to the central nervous system.

Eligibility criteria: Inclusion Criteria:

1. Subjects with pathologically confirmed colorectal carcinoma that is metastatic or unresectable and which is refractory to standard therapy. To be considered refractory, a subject must have experienced progression (or intolerance) after treatment with standard approved regimens including, oxaliplatin, irinotecan flouropyrimidine, bevacizumab, and cetuximab or panitumumab if KRAS wildtype.
2. Subjects will not be treated with any radiation, chemotherapy, or investigational agents while enrolled in this protocol.
3. Eastern Cooperative Oncology Group (ECOG) performance status 0,1, or 2.
4. At least 2 weeks since the last previous cancer treatment including: chemotherapy, radiation therapy, immunotherapy, surgery, hormonal therapy, or targeted biologics.
5. Age ≥ 18 years, male or female subjects.
6. Serum potassium and magnesium levels within institutional normal limits. Total serum calcium or ionized calcium level must be greater than or equal to the lower limit of normal.
7. Adequate renal function, defined by serum creatinine ≤ 1.5 x ULN.
8. Adequate hepatic function
9. Adequate bone marrow function
10. For women of childbearing potential (WOCBP), a negative serum pregnancy test result at Screening.
11. Signed and dated institutional review board (IRB)-approved informed consent before any protocol-specific screening procedures are performed.
12. Patients enrolled must, in the Investigator's judgment, be healthy enough to stay on the clinical trial for three months.

Exclusion Criteria:

1. Mechanical obstruction that would prevent adequate oral nutritional intake.
2. Serious uncontrolled medical disorder, or active infection, that would impair the ability of the patient to receive protocol therapy.
3. Uncontrolled or significant cardiovascular disease, including:
4. Dementia or altered mental status that would prohibit the understanding or rendering of informed consent.
5. Subjects who have not recovered from the adverse effects of prior therapy at the time of enrollment to ≤ grade 1; excluding alopecia and grade 2 neuropathy.
6. Immunocompromised subjects, including subjects known to be infected with human immunodeficiency virus (HIV).
7. Known hepatitis B surface antigen and/or positive hepatitis C antibody and presence of hepatitis C RNA.
8. History of tuberculosis (latent or active) or positive Interferon-gamma release assay (IGRA).
9. Receipt of a live (attenuated) vaccine within 1 month prior to Screening
10. Subjects with history of hypersensitivity to compounds of similar chemical or biologic composition of XILONIX™.
11. Women who are pregnant or breastfeeding.
12. WOCBP or men whose sexual partners are WOCBP who are unwilling or unable to use an acceptable method of contraception for at least 1 month prior to study entry, for the duration of the study, and for at least 3 months after the last dose of study medication.
13. Weight loss \>20% in the previous 6 months.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to 18 months
Secondary outcomes:
measure: Change From Baseline in Lean Body Mass (LBM) Measured by Dual-energy X-ray Absorptiometry (DEXA) Scans
timeFrame: Baseline and Week 8
measure: Change From Baseline in Symptom Scale and Global Health Status/Quality of Life (QoL) Assessed Through the Cancer-specific European Organization for Research and Treatment of Cancer - Quality of Life Questionnaire (EORTC QLQ-C30)
timeFrame: Baseline and Week 8
measure: Change From Baseline in Platelet Counts
timeFrame: Baseline and Week 8
measure: Progression Free Survival (PFS)
timeFrame: Up to 18 Months
measure: Percentage of Participants With Objective Response (OR)
timeFrame: Up to 18 months
measure: Percentage of Participants With Disease Control
timeFrame: Up to 18 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Oncology, Bruno Cancer Center
state: Alabama
city: Mobile
country: United States
facility: Southern Cancer Center, PC
state: Alabama
city: Muscle Shoals
country: United States
facility: Northwest Alabama Cancer Center, PC
state: Alabama
city: Tucson
country: United States
facility: Arizona Oncology Associates
state: Arizona
city: Anaheim
country: United States
facility: Pacific Cancer Medical Center, Inc.
state: California
city: Fresno
country: United States
facility: California Cancer Associates for Research and Excellence, Inc. (cCARE)
state: California
city: Fullerton
country: United States
facility: St. Jude Medical Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center and LAC USC Medical Center
state: California
city: Oxnard
country: United States
facility: Ventura County Hematology-Oncology Specialists
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Institute
state: California
city: Whittier
country: United States
facility: American Institute of Research
state: California
city: Miami
country: United States
facility: Advanced Medical Specialists
state: Florida
city: Thomasville
country: United States
facility: Lewis Hall Singletary Oncology Center
state: Georgia
city: Chicago
country: United States
facility: Swedish Covenant Hospital via Clintell, Inc.
state: Illinois
city: Harvey
country: United States
facility: Ingalls Memorial Hospital
state: Illinois
city: Hines
country: United States
facility: Hines VA Hospital
state: Illinois
city: Park Ridge
country: United States
facility: Oncology Specialists, SC
state: Illinois
city: Indianapolis
country: United States
facility: Franciscan St. Francis Health
state: Indiana
city: Hutchinson
country: United States
facility: Hutchinson Clinic, P.A.
state: Kansas
city: Louisville
country: United States
facility: James Graham Brown Cancer Center
state: Kentucky
city: Bethesda
country: United States
facility: The Center for Cancer and Blood Disorders, a Division of Regional Cancer Care Associates LLC.
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: Park Nicollet
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: East Setauket
country: United States
facility: North Shore Hematology Oncology Associates, PC
state: New York
city: Mount Kisco
country: United States
facility: Northern Westchester Hospital
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Stony Brook
country: United States
facility: Stony Brook Cancer Center
state: New York
city: Washington
country: United States
facility: East Carolina Health - Beaufort, Inc. DBA Marion L. Shepard Cancer Center
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care
state: Ohio
city: Sylvania
country: United States
facility: ProMedica Flower Hospital
state: Ohio
city: Bend
country: United States
facility: St. Charles Health System, Inc.
state: Oregon
city: Corvallis
country: United States
facility: Good Samaritan Hospital Corvallis - SHOC
state: Oregon
city: Bethlehem
country: United States
facility: St. Luke's University Health Network
state: Pennsylvania
city: Philadelphia
country: United States
facility: Albert Einstein Cancer Center
state: Pennsylvania
city: Charleston
country: United States
facility: Charleston Hematology Oncology Associates, PA
state: South Carolina
city: Greenville
country: United States
facility: Bon Secours Saint Francis Cancer Center
state: South Carolina
city: Bedford
country: United States
facility: Texas Oncology
state: Texas
city: Corpus Christi
country: United States
facility: Coastal Bend Cancer Center
state: Texas
city: Dallas
country: United States
facility: Mary Crowley Cancer Research Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Dallas
state: Texas
city: Grapevine
country: United States
facility: Texas Oncology - Grapevine
state: Texas
city: Houston
country: United States
facility: Millennium Oncology
state: Texas
city: Richardson
country: United States
facility: Methodist Richardson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Brooke Army Medical Center
state: Texas
city: Temple
country: United States
facility: Scott & White Healthcare
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Longview and Tyler
state: Texas
city: Tyler
country: United States
facility: University of TX Health Science Center at Tyler
state: Texas
city: Multiple Locations
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Everett
country: United States
facility: Providence Regional Medical Center Everett, PRCP - Clinical Research
state: Washington
city: Kirkland
country: United States
facility: SCCA - Evergreen Health
state: Washington
city: Multiple Locations
country: United States
facility: University of Washington
state: Washington
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Seattle
country: United States
facility: SCCA - Group Health
state: Washington
city: St Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane & Women's Hospital
state: Queensland
city: Elizabeth Vale
country: Australia
facility: Lyell McEwin Hospital
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Saint Albans
country: Australia
facility: Western Health - Sunshine Hospital
state: Victoria
city: Linz
country: Austria
facility: Hospital Barmherzige Schwestern Linz
city: Linz
country: Austria
facility: Krankenhaus der Barmherzigen Schwestern Linz
city: Salzburg
country: Austria
facility: LKH Salzburg 3rd Medical Department with Hematology
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen GmbH, IV. Internal Department
city: Charleroi
country: Belgium
facility: Grand HÃ´pital de Charleroi, Grand Rue 3
state: Hainaut
city: Yvoir
country: Belgium
facility: CHU Dinant Godinne UCL Namur
state: Namur
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Edegem
country: Belgium
facility: Antwerp University Hospital
city: Liège
country: Belgium
facility: Domaine Universitaire du Sart Tilman
city: Brno
country: Czechia
facility: Masarykův onkologický ústav
city: Praha
country: Czechia
facility: Všeobecné fakultní nemocnice v Praze, Onkologická klinika
city: Praha
country: Czechia
facility: Thomayerova nemocnice, Onkologická klinika 1.LF TN Praha
city: Praha
country: Czechia
facility: Fakultní nemocnice v Motole, Komplexní onkologické centrum
city: Budapest
country: Hungary
facility: Semmelweis University 1st Dept. Of Internal Medicine, Oncology Division
city: Budapest
country: Hungary
facility: "B" Dept. Of Internal Medicine, National Institute of Oncology
city: Budapest
country: Hungary
facility: Uzsoki Hospital, Dept. of Oncoradiology
city: Kaposvár
country: Hungary
facility: Dept. Of Oncology, Somogy County Kaposi Mor Teaching Hospital
city: Szekszárd
country: Hungary
facility: Dept. Of Oncology, Tolna County Balassa Janos Hospital
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Brescia
country: Italy
facility: FONDAZIONE POLIAMBULANZA â€" ISTITUTO OSPEDALIERO
city: Cona
country: Italy
facility: A.O. Universitaria Arcispedale S.Anna Di Ferrara
city: Pisa
country: Italy
facility: Azienda Ospedaliera University Pisana Uo Oncol Medica 2
city: Pontedera
country: Italy
facility: U.O. Oncologia Medica
city: Rome
country: Italy
facility: San Giovanni Calibita" Fatebenefratelli Hospital
city: Amsterdam
country: Netherlands
facility: Academic Medical Centre Amsterdam
city: Breda
country: Netherlands
facility: Amphia Hospital
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht Heidelberglaan
city: Białystok
country: Poland
facility: Bialostockie Centrum Onkologii im. Marii Sklodowskiej-Curie w Bialymstoku Odzial Onkologii Klinicznej
city: Bydgoszcz
country: Poland
facility: Regionalne Centrum Onkologii Szpitala im. Prof. Franciszka Łukaszczyka
city: Gdynia
country: Poland
facility: Szpital Wojewodzki w Gdyni Sp. Z o.o., Szpital Morski im PCK
city: Konin
country: Poland
facility: Przychodnia Lekarska "Komed"
city: Kraków
country: Poland
facility: NZOZ Vesalius
city: Olsztyn
country: Poland
facility: Samodzielny Publiczny ZOZ MSZ z Warmińsko-Mazurskim Centrum Onkologii w Olsztynie
city: Warszawa
country: Poland
facility: Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie, Klinika Gastroenterologii Onkologicznej
city: Warszawa
country: Poland
facility: NZOZ Magodent sp z.o.o.
city: Barcelona
country: Spain
facility: Instituto OncolÃ³gico Dr. Rosell.
city: Barcelona
country: Spain
facility: Hospital Vall Dhebron Edificio Principal Planta Baja
city: Barcelona
country: Spain
facility: Institut CatalÃ d'Oncologia, Hospital Duran i Reynals
city: Barcelona
country: Spain
facility: Institut CatalÃ d'Oncologia
city: Benidorm
country: Spain
facility: Hospital ClÃ-nica Benidorm
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital 12 De Octubre
city: Madrid
country: Spain
facility: CIOCC, Centro Integral OncolÃ³gico Clara Campal
city: Palma
country: Spain
facility: Hospital Son LlÃ tzer
city: Valencia
country: Spain
facility: Hospital Universitario La Fe, Consultas Externas Oncologia
city: Bellinzona
country: Switzerland
facility: Istituto Oncologico della Svizzera Italiania
city: Chur
country: Switzerland
facility: Kantonsspital GraubÃnden
city: Manchester
country: United Kingdom
facility: Christie Hospital
state: Greater Manchester
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital
state: Surrey
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Hong DS, Hui D, Bruera E, Janku F, Naing A, Falchook GS, Piha-Paul S, Wheler JJ, Fu S, Tsimberidou AM, Stecher M, Mohanty P, Simard J, Kurzrock R. MABp1, a first-in-class true human antibody targeting interleukin-1alpha in refractory cancers: an open-label, phase 1 dose-escalation and expansion study. Lancet Oncol. 2014 May;15(6):656-66. doi: 10.1016/S1470-2045(14)70155-X. Epub 2014 Apr 17.