A Phase III Study of Xilonix in Patients With Advanced Colorectal Cancer
- Registration Number
- NCT01767857
- Lead Sponsor
- Janssen Research & Development, LLC
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 643
- 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.
- Subjects will not be treated with any radiation, chemotherapy, or investigational agents while enrolled in this protocol.
- Eastern Cooperative Oncology Group (ECOG) performance status 0,1, or 2.
- At least 2 weeks since the last previous cancer treatment including: chemotherapy, radiation therapy, immunotherapy, surgery, hormonal therapy, or targeted biologics.
- Age ≥ 18 years, male or female subjects.
- 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.
- Adequate renal function, defined by serum creatinine ≤ 1.5 x ULN.
- Adequate hepatic function
- Adequate bone marrow function
- For women of childbearing potential (WOCBP), a negative serum pregnancy test result at Screening.
- Signed and dated institutional review board (IRB)-approved informed consent before any protocol-specific screening procedures are performed.
- Patients enrolled must, in the Investigator's judgment, be healthy enough to stay on the clinical trial for three months.
- Mechanical obstruction that would prevent adequate oral nutritional intake.
- Serious uncontrolled medical disorder, or active infection, that would impair the ability of the patient to receive protocol therapy.
- Uncontrolled or significant cardiovascular disease, including:
- Dementia or altered mental status that would prohibit the understanding or rendering of informed consent.
- 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.
- Immunocompromised subjects, including subjects known to be infected with human immunodeficiency virus (HIV).
- Known hepatitis B surface antigen and/or positive hepatitis C antibody and presence of hepatitis C RNA.
- History of tuberculosis (latent or active) or positive Interferon-gamma release assay (IGRA).
- Receipt of a live (attenuated) vaccine within 1 month prior to Screening
- Subjects with history of hypersensitivity to compounds of similar chemical or biologic composition of XILONIX™.
- Women who are pregnant or breastfeeding.
- 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.
- Weight loss >20% in the previous 6 months.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo administered IV every two weeks, plus best supportive care Xilonix Xilonix MABp1 administered IV every two weeks, plus best supportive care
- Primary Outcome Measures
Name Time Method Overall Survival (OS) Up to 18 months Overall survival time was defined as the duration from the date of randomization until death or last follow-up. OS was summarized by Kaplan-Meier method and compared between the treatment groups using un-adjusted log-rank test.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Platelet Counts Baseline and Week 8 Change from baseline in platelet counts up to Week 8 was evaluated.
Change From Baseline in Lean Body Mass (LBM) Measured by Dual-energy X-ray Absorptiometry (DEXA) Scans Baseline and Week 8 Change from baseline in LBM as measured by Dexa scans was reported. DEXA is an X-ray imaging modality used to determine the mass of one material in the presence of another material, using the knowledge of their unique X-ray attenuation at different energies.
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) Baseline and Week 8 The EORTC QLQ-C30 questionnaire incorporates nine multi-item scales: 5 functional scales (physical, cognitive, role, emotional, and social); 3 symptom scales (pain, fatigue, and appetite loss) and a Global Health Status/QoL scale. Each item, except Global Health Status, is answered on a four-point scale (1-4): 1-not at all, 2-a little, 3-quite a bit, 4-very much. Response to Global Health Status is measured on a 1 to 7 scale. "1" being very poor and "7" being excellent. Each scale (symptom scale \[pain, fatigue, and appetite loss\] and Global Health Status/Quality of Life \[QoL\] scale) was linearly transformed to be in range from 0-100 where a higher score represents good health status, while lower scores indicate poor health status. As planned, the data for symptom scales (pain, fatigue, appetite loss) and a Global Health Status/QoL scale was evaluated and reported.
Progression Free Survival (PFS) Up to 18 Months PFS was defined as time from randomization to tumor progression or death. Progressive Disease defined as increase in tumor burden greater than or equals to (\>=) 25 (%) percent relative to nadir (minimum recorded tumor burden) confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented. Participants surviving without disease progression at end of study were censored. PFS was compared by Kaplan-Meier method using log-rank test.
Percentage of Participants With Objective Response (OR) Up to 18 months The percentage of OR was estimated by dividing the total number of confirmed complete response (CR) and partial response (PR) by the total number of participants randomized where CR was complete disappearance of all lesions (whether measurable or not, and no new lesions); confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented and PR was decrease in tumor burden \>= 50 % relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation.
Percentage of Participants With Disease Control Up to 18 months Percentage of participants who achieved disease control was estimated by dividing the total number of confirmed CRs, PRs and stable disease (SD) by the total number of participants randomized where CR was complete disappearance of all lesions (whether measurable or not, and no new lesions); confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented, PR was decrease in tumor burden \>= 50% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation and SD defined as not meeting criteria for CR and PR, in absence of Progressive Disease (increase in tumor burden \>= 25 % relative to nadir (minimum recorded tumor burden) confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented).
Trial Locations
- Locations (113)
The Center for Cancer and Blood Disorders, a Division of Regional Cancer Care Associates LLC.
🇺🇸Bethesda, Maryland, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Good Samaritan Hospital Corvallis - SHOC
🇺🇸Corvallis, Oregon, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Lyell McEwin Hospital
🇦🇺Elizabeth Vale, South Australia, Australia
Charleston Hematology Oncology Associates, PA
🇺🇸Charleston, South Carolina, United States
St. Charles Health System, Inc.
🇺🇸Bend, Oregon, United States
LKH Salzburg 3rd Medical Department with Hematology
🇦🇹Salzburg, Austria
Cliniques Universitaires Saint-Luc
🇧🇪Brussels, Belgium
"B" Dept. Of Internal Medicine, National Institute of Oncology
🇭🇺Budapest, Hungary
Klinikum Wels-Grieskirchen GmbH, IV. Internal Department
🇦🇹Wels, Austria
Grand Hôpital de Charleroi, Grand Rue 3
🇧🇪Charleroi, Hainaut, Belgium
U.O. Oncologia Medica
🇮🇹Pontedera, Italy
Szpital Wojewodzki w Gdyni Sp. Z o.o., Szpital Morski im PCK
🇵🇱Gdynia, Poland
Institut Jules Bordet
🇧🇪Brussels, Belgium
Dept. Of Oncology, Tolna County Balassa Janos Hospital
🇭🇺Szekszárd, Hungary
FONDAZIONE POLIAMBULANZA â€" ISTITUTO OSPEDALIERO
🇮🇹Brescia, Italy
A.O. Universitaria Arcispedale S.Anna Di Ferrara
🇮🇹Cona, Italy
Uzsoki Hospital, Dept. of Oncoradiology
🇭🇺Budapest, Hungary
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Azienda Ospedaliera University Pisana Uo Oncol Medica 2
🇮🇹Pisa, Italy
Academic Medical Centre Amsterdam
🇳🇱Amsterdam, Netherlands
University Medical Center Utrecht Heidelberglaan
🇳🇱Utrecht, Netherlands
Istituto Oncologico della Svizzera Italiania
🇨🇭Bellinzona, Switzerland
Kantonsspital GraubÃnden
🇨🇭Chur, Switzerland
Northwest Alabama Cancer Center, PC
🇺🇸Muscle Shoals, Alabama, United States
Pacific Cancer Medical Center, Inc.
🇺🇸Anaheim, California, United States
Stony Brook Cancer Center
🇺🇸Stony Brook, New York, United States
Mary Crowley Cancer Research Center
🇺🇸Dallas, Texas, United States
SCCA - Group Health
🇺🇸Seattle, Washington, United States
Royal Brisbane & Women's Hospital
🇦🇺Herston, Queensland, Australia
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Stanford Cancer Institute
🇺🇸Palo Alto, California, United States
American Institute of Research
🇺🇸Whittier, California, United States
Advanced Medical Specialists
🇺🇸Miami, Florida, United States
Lewis Hall Singletary Oncology Center
🇺🇸Thomasville, Georgia, United States
Park Nicollet
🇺🇸Minneapolis, Minnesota, United States
ProMedica Flower Hospital
🇺🇸Sylvania, Ohio, United States
Bon Secours Saint Francis Cancer Center
🇺🇸Greenville, South Carolina, United States
Texas Oncology - Grapevine
🇺🇸Grapevine, Texas, United States
Brooke Army Medical Center
🇺🇸San Antonio, Texas, United States
Scott & White Healthcare
🇺🇸Temple, Texas, United States
University of TX Health Science Center at Tyler
🇺🇸Tyler, Texas, United States
Virginia Oncology Associates
🇺🇸Multiple Locations, Virginia, United States
University of Washington
🇺🇸Multiple Locations, Washington, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Royal North Shore Hospital
🇦🇺St Leonards, New South Wales, Australia
Western Health - Sunshine Hospital
🇦🇺Saint Albans, Victoria, Australia
Hospital Barmherzige Schwestern Linz
🇦🇹Linz, Austria
Domaine Universitaire du Sart Tilman
🇧🇪Liège, Belgium
Všeobecné fakultní nemocnice v Praze, Onkologická klinika
🇨🇿Praha, Czechia
Antwerp University Hospital
🇧🇪Edegem, Belgium
Masarykův onkologický ústav
🇨🇿Brno, Czechia
Fakultní nemocnice v Motole, Komplexní onkologické centrum
🇨🇿Praha, Czechia
Thomayerova nemocnice, Onkologická klinika 1.LF TN Praha
🇨🇿Praha, Czechia
Semmelweis University 1st Dept. Of Internal Medicine, Oncology Division
🇭🇺Budapest, Hungary
Dept. Of Oncology, Somogy County Kaposi Mor Teaching Hospital
🇭🇺Kaposvár, Hungary
San Giovanni Calibita" Fatebenefratelli Hospital
🇮🇹Rome, Italy
Amphia Hospital
🇳🇱Breda, Netherlands
Regionalne Centrum Onkologii Szpitala im. Prof. Franciszka Łukaszczyka
🇵🇱Bydgoszcz, Poland
Przychodnia Lekarska "Komed"
🇵🇱Konin, Poland
NZOZ Vesalius
🇵🇱Kraków, Poland
NZOZ Magodent sp z.o.o.
🇵🇱Warszawa, Poland
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Samodzielny Publiczny ZOZ MSZ z Warmińsko-Mazurskim Centrum Onkologii w Olsztynie
🇵🇱Olsztyn, Poland
Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie, Klinika Gastroenterologii Onkologicznej
🇵🇱Warszawa, Poland
Instituto Oncológico Dr. Rosell.
🇪🇸Barcelona, Spain
Hospital Vall Dhebron Edificio Principal Planta Baja
🇪🇸Barcelona, Spain
Institut Català d'Oncologia, Hospital Duran i Reynals
🇪🇸Barcelona, Spain
Hospital Universitario La Fe, Consultas Externas Oncologia
🇪🇸Valencia, Spain
The Royal Marsden Hospital
🇬🇧Sutton, Surrey, United Kingdom
CHU Dinant Godinne UCL Namur
🇧🇪Yvoir, Namur, Belgium
Royal Hobart Hospital
🇦🇺Hobart, Tasmania, Australia
Krankenhaus der Barmherzigen Schwestern Linz
🇦🇹Linz, Austria
Rambam Health Care Campus
🇮🇱Haifa, Israel
Bialostockie Centrum Onkologii im. Marii Sklodowskiej-Curie w Bialymstoku Odzial Onkologii Klinicznej
🇵🇱Białystok, Poland
Hospital ClÃ-nica Benidorm
🇪🇸Benidorm, Spain
Arizona Oncology Associates
🇺🇸Tucson, Arizona, United States
Alabama Oncology, Bruno Cancer Center
🇺🇸Birmingham, Alabama, United States
Southern Cancer Center, PC
🇺🇸Mobile, Alabama, United States
USC Norris Comprehensive Cancer Center and LAC USC Medical Center
🇺🇸Los Angeles, California, United States
Institut Català d'Oncologia
🇪🇸Barcelona, Spain
Ventura County Hematology-Oncology Specialists
🇺🇸Oxnard, California, United States
Hospital 12 De Octubre
🇪🇸Madrid, Spain
Hospital Son Llà tzer
🇪🇸Palma, Spain
Ingalls Memorial Hospital
🇺🇸Harvey, Illinois, United States
Hutchinson Clinic, P.A.
🇺🇸Hutchinson, Kansas, United States
Swedish Covenant Hospital via Clintell, Inc.
🇺🇸Chicago, Illinois, United States
Oncology Specialists, SC
🇺🇸Park Ridge, Illinois, United States
Hines VA Hospital
🇺🇸Hines, Illinois, United States
Christie Hospital
🇬🇧Manchester, Greater Manchester, United Kingdom
Franciscan St. Francis Health
🇺🇸Indianapolis, Indiana, United States
Albert Einstein Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Oncology Hematology Care
🇺🇸Cincinnati, Ohio, United States
East Carolina Health - Beaufort, Inc. DBA Marion L. Shepard Cancer Center
🇺🇸Washington, North Carolina, United States
Coastal Bend Cancer Center
🇺🇸Corpus Christi, Texas, United States
St. Luke's University Health Network
🇺🇸Bethlehem, Pennsylvania, United States
Texas Oncology - Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
Texas Oncology - Longview and Tyler
🇺🇸Tyler, Texas, United States
Methodist Richardson Cancer Center
🇺🇸Richardson, Texas, United States
CIOCC, Centro Integral Oncológico Clara Campal
🇪🇸Madrid, Spain
California Cancer Associates for Research and Excellence, Inc. (cCARE)
🇺🇸Fresno, California, United States
North Shore Hematology Oncology Associates, PC
🇺🇸East Setauket, New York, United States
Northern Westchester Hospital
🇺🇸Mount Kisco, New York, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Texas Oncology - Dallas
🇺🇸Dallas, Texas, United States
Millennium Oncology
🇺🇸Houston, Texas, United States
Texas Oncology
🇺🇸Bedford, Texas, United States
SCCA - Evergreen Health
🇺🇸Kirkland, Washington, United States
St. Jude Medical Center
🇺🇸Fullerton, California, United States
James Graham Brown Cancer Center
🇺🇸Louisville, Kentucky, United States
Providence Regional Medical Center Everett, PRCP - Clinical Research
🇺🇸Everett, Washington, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States