A Phase III Study of Xilonix in Patients With Advanced Colorectal Cancer (XCITE)

Phase III Double-blinded, Placebo Controlled Study of Xilonix™ for Improving Survival in Metastatic Colorectal Cancer

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.

Study Overview

• Status: Terminated
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: Xilonix; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 643
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane & Women's Hospital
  • South Australia
    • Elizabeth Vale, South Australia, Australia, 5112
      • Lyell McEwin Hospital
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Royal Hobart Hospital
  • Victoria
    • Saint Albans, Victoria, Australia, 3021
      • Western Health - Sunshine Hospital
• Austria
  • Linz, Austria, 4010
    • Krankenhaus Der Barmherzigen Schwestern Linz
  • Linz, Austria, 4010
    • Hospital Barmherzige Schwestern Linz
  • Salzburg, Austria, 5020
    • LKH Salzburg 3rd Medical Department with Hematology
  • Wels, Austria, 4600
    • Klinikum Wels-Grieskirchen GmbH, IV. Internal Department
• Belgium
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint-luc
  • Brussels, Belgium, 1000
    • Institut Jules Bordet
  • Edegem, Belgium, 2650
    • Antwerp University Hospital
  • Liège, Belgium, 4000
    • Domaine Universitaire du Sart Tilman
  • Hainaut
    • Charleroi, Hainaut, Belgium, 6000
      • Grand Hôpital de Charleroi, Grand Rue 3
  • Namur
    • Yvoir, Namur, Belgium, 5530
      • CHU Dinant Godinne UCL Namur
• Czechia
  • Brno, Czechia, 65653
    • Masarykuv onkologicky ustav
  • Praha, Czechia, 12808
    • Všeobecné fakultní nemocnice v Praze, Onkologická klinika
  • Praha, Czechia, 14059
    • Thomayerova nemocnice, Onkologická klinika 1.LF TN Praha
  • Praha, Czechia, 15006
    • Fakultní nemocnice v Motole, Komplexní onkologické centrum
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis University 1st Dept. Of Internal Medicine, Oncology Division
  • Budapest, Hungary, 1122
    • "B" Dept. Of Internal Medicine, National Institute of Oncology
  • Budapest, Hungary, 1145
    • Uzsoki Hospital, Dept. of Oncoradiology
  • Kaposvár, Hungary, 7400
    • Dept. Of Oncology, Somogy County Kaposi Mor Teaching Hospital
  • Szekszárd, Hungary, 7100
    • Dept. Of Oncology, Tolna County Balassa Janos Hospital
• Israel
  • Haifa, Israel, 31096
    • Rambam Health Care Campus
  • Tel Aviv, Israel
    • Tel Aviv Sourasky Medical Center
• Italy
  • Brescia, Italy, 25124
    • FONDAZIONE POLIAMBULANZA â€" ISTITUTO OSPEDALIERO
  • Cona, Italy, 44124
    • A.O. Universitaria Arcispedale S.Anna Di Ferrara
  • Pisa, Italy, 56126
    • Azienda Ospedaliera University Pisana Uo Oncol Medica 2
  • Pontedera, Italy, 56025
    • U.O. Oncologia Medica
  • Rome, Italy, 186
    • San Giovanni Calibita" Fatebenefratelli Hospital
• Netherlands
  • Amsterdam, Netherlands, 1105AZ
    • Academic Medical Centre Amsterdam
  • Breda, Netherlands, 4819EV
    • Amphia Hospital
  • Utrecht, Netherlands, 3584CX
    • University Medical Center Utrecht Heidelberglaan
• Poland
  • Białystok, Poland, 15027
    • Bialostockie Centrum Onkologii im. Marii Sklodowskiej-Curie w Bialymstoku Odzial Onkologii Klinicznej
  • Bydgoszcz, Poland, 85796
    • Regionalne Centrum Onkologii Szpitala im. Prof. Franciszka Łukaszczyka
  • Gdynia, Poland, 81519
    • Szpital Wojewodzki w Gdyni Sp. Z o.o., Szpital Morski im PCK
  • Konin, Poland, 62500
    • Przychodnia Lekarska "Komed"
  • Kraków, Poland, 31108
    • NZOZ Vesalius
  • Olsztyn, Poland, 10228
    • Samodzielny Publiczny ZOZ MSZ z Warmińsko-Mazurskim Centrum Onkologii w Olsztynie
  • Warszawa, Poland, 02781
    • Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie, Klinika Gastroenterologii Onkologicznej
  • Warszawa, Poland, 04125
    • NZOZ Magodent sp z.o.o.
• Spain
  • Barcelona, Spain, 8028
    • Instituto Oncológico Dr. Rosell.
  • Barcelona, Spain, 8035
    • Hospital Vall Dhebron Edificio Principal Planta Baja
  • Barcelona, Spain, 8907
    • Institut Catalá d'Oncologia, Hospital Duran i Reynals
  • Barcelona, Spain, 8916
    • Institut Catala d'Oncologia
  • Benidorm, Spain, 3501
    • Hospital ClÃ-nica Benidorm
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28041
    • Hospital 12 de Octubre
  • Madrid, Spain, 28050
    • CIOCC, Centro Integral Oncológico Clara Campal
  • Palma, Spain, 7198
    • Hospital Son Llà tzer
  • Valencia, Spain, 46026
    • Hospital Universitario La Fe, Consultas Externas Oncologia
• Switzerland
  • Bellinzona, Switzerland, 6500
    • Istituto Oncologico della Svizzera Italiania
  • Chur, Switzerland, 7000
    • Kantonsspital GraubÃnden
• United Kingdom
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom
      • Christie Hospital
  • Surrey
    • Sutton, Surrey, United Kingdom
      • The Royal Marsden Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Alabama Oncology, Bruno Cancer Center
    • Mobile, Alabama, United States, 36608
      • Southern Cancer Center, PC
    • Muscle Shoals, Alabama, United States, 35661
      • Northwest Alabama Cancer Center, Pc
  • Arizona
    • Tucson, Arizona, United States
      • Arizona Oncology Associates
  • California
    • Anaheim, California, United States, 92801
      • Pacific Cancer Medical Center, Inc.
    • Fresno, California, United States, 93720
      • California Cancer Associates for Research and Excellence, Inc. (cCARE)
    • Fullerton, California, United States, 92835
      • St. Jude Medical Center
    • Los Angeles, California, United States
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States
      • USC Norris Comprehensive Cancer Center and LAC USC Medical Center
    • Oxnard, California, United States, 93030
      • Ventura County Hematology-Oncology Specialists
    • Palo Alto, California, United States, 94304
      • Stanford Cancer Institute
    • Whittier, California, United States, 90603
      • American Institute of Research
  • Florida
    • Miami, Florida, United States
      • Advanced Medical Specialists
  • Georgia
    • Thomasville, Georgia, United States, 31792
      • Lewis Hall Singletary Oncology Center
  • Illinois
    • Chicago, Illinois, United States, 60625
      • Swedish Covenant Hospital via Clintell, Inc.
    • Harvey, Illinois, United States, 60426
      • Ingalls Memorial Hospital
    • Hines, Illinois, United States, 60141
      • Hines VA Hospital
    • Park Ridge, Illinois, United States, 60068
      • Oncology Specialists, SC
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Franciscan St. Francis Health
  • Kansas
    • Hutchinson, Kansas, United States, 67502
      • Hutchinson Clinic, P.A.
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • James Graham Brown Cancer Center
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • The Center for Cancer and Blood Disorders, a Division of Regional Cancer Care Associates LLC.
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55416
      • Park Nicollet
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • East Setauket, New York, United States, 11733
      • North Shore Hematology Oncology Associates, PC
    • Mount Kisco, New York, United States, 10549
      • Northern Westchester Hospital
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
    • Stony Brook, New York, United States, 11794
      • Stony Brook Cancer Center
  • North Carolina
    • Washington, North Carolina, United States, 27889
      • East Carolina Health - Beaufort, Inc. DBA Marion L. Shepard Cancer Center
  • Ohio
    • Cincinnati, Ohio, United States
      • Oncology Hematology Care
    • Sylvania, Ohio, United States, 43560
      • ProMedica Flower Hospital
  • Oregon
    • Bend, Oregon, United States, 97701
      • St. Charles Health System, Inc.
    • Corvallis, Oregon, United States, 97330
      • Good Samaritan Hospital Corvallis - SHOC
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • St. Luke's University Health network
    • Philadelphia, Pennsylvania, United States, 19141
      • Albert Einstein Cancer Center
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Charleston Hematology Oncology Associates, PA
    • Greenville, South Carolina, United States, 29651
      • Bon Secours Saint Francis Cancer Center
  • Texas
    • Bedford, Texas, United States, 76022
      • Texas Oncology
    • Corpus Christi, Texas, United States, 78404
      • Coastal Bend Cancer Center
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research Center
    • Dallas, Texas, United States, 75246
      • Texas Oncology - Baylor Charles A. Sammons Cancer Center
    • Dallas, Texas, United States
      • Texas Oncology - Dallas
    • Grapevine, Texas, United States, 76051
      • Texas Oncology - Grapevine
    • Houston, Texas, United States, 77090
      • Millennium Oncology
    • Richardson, Texas, United States, 75802
      • Methodist Richardson Cancer Center
    • San Antonio, Texas, United States, 78234
      • Brooke Army Medical Center
    • Temple, Texas, United States, 76508
      • Scott & White Healthcare
    • Tyler, Texas, United States
      • Texas Oncology - Longview and Tyler
    • Tyler, Texas, United States
      • University of TX Health Science Center at Tyler
  • Virginia
    • Multiple Locations, Virginia, United States
      • Virginia Oncology Associates
  • Washington
    • Everett, Washington, United States, 98201
      • Providence Regional Medical Center Everett, PRCP - Clinical Research
    • Kirkland, Washington, United States, 98034
      • SCCA - Evergreen Health
    • Multiple Locations, Washington, United States
      • University of Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance
    • Seattle, Washington, United States, 98112
      • SCCA - Group Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Xilonix; MABp1 administered IV every two weeks, plus best supportive care	Drug: Xilonix; Xilonix is a True Human Monoclonal Antibody targeting Interleukin 1 alpha, and is administered intravenously every 2 weeks with best supportive care until clinical or radiographic progression.; Other Names: MABp1, CA-18C3
PLACEBO_COMPARATOR: Placebo; Placebo administered IV every two weeks, plus best supportive care	Drug: Placebo; Placebo plus best supportive care will be administered intravenously every 2 weeks until clinical or radiographic progression.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	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.	Up to 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Lean Body Mass (LBM) Measured by Dual-energy X-ray Absorptiometry (DEXA) Scans	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.	Baseline and Week 8
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)	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.	Baseline and Week 8
Change From Baseline in Platelet Counts	Change from baseline in platelet counts up to Week 8 was evaluated.	Baseline and Week 8
Progression Free Survival (PFS)	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.	Up to 18 Months
Percentage of Participants With Objective Response (OR)	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.	Up to 18 months
Percentage of Participants With Disease Control	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).	Up to 18 months

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 31, 2013
• Primary Completion (ACTUAL): June 30, 2017
• Study Completion (ACTUAL): June 30, 2017

Study Registration Dates

• First Submitted: January 8, 2013
• First Submitted That Met QC Criteria: January 10, 2013
• First Posted (ESTIMATE): January 14, 2013

Study Record Updates

• Last Update Posted (ACTUAL): June 29, 2021
• Last Update Submitted That Met QC Criteria: June 28, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Survival; Phase 3; Colorectal; Pivotal
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: 2012-PT023