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

NCT ID: NCT01767857

Last Updated: 2021-06-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 643 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-31
• Study Completion Date: 2017-06-30

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.

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Xilonix

MABp1 administered IV every two weeks, plus best supportive care

Group Type: EXPERIMENTAL

Xilonix

Intervention Type: DRUG

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.

Placebo

Placebo administered IV every two weeks, plus best supportive care

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo plus best supportive care will be administered intravenously every 2 weeks until clinical or radiographic progression.

Interventions

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.

Intervention Type: DRUG

Placebo

Placebo plus best supportive care will be administered intravenously every 2 weeks until clinical or radiographic progression.

Intervention Type: DRUG

Other Intervention Names

MABp1, CA-18C3

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Alabama Oncology, Bruno Cancer Center

Birmingham, Alabama, United States

Southern Cancer Center, PC

Mobile, Alabama, United States

Northwest Alabama Cancer Center, PC

Muscle Shoals, Alabama, United States

Arizona Oncology Associates

Tucson, Arizona, United States

Pacific Cancer Medical Center, Inc.

Anaheim, California, United States

California Cancer Associates for Research and Excellence, Inc. (cCARE)

Fresno, California, United States

St. Jude Medical Center

Fullerton, California, United States

Cedars-Sinai Medical Center

Los Angeles, California, United States

USC Norris Comprehensive Cancer Center and LAC USC Medical Center

Los Angeles, California, United States

Ventura County Hematology-Oncology Specialists

Oxnard, 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

Swedish Covenant Hospital via Clintell, Inc.

Chicago, Illinois, United States

Ingalls Memorial Hospital

Harvey, Illinois, United States

Hines VA Hospital

Hines, Illinois, United States

Oncology Specialists, SC

Park Ridge, Illinois, United States

Franciscan St. Francis Health

Indianapolis, Indiana, United States

Hutchinson Clinic, P.A.

Hutchinson, Kansas, United States

James Graham Brown Cancer Center

Louisville, Kentucky, United States

The Center for Cancer and Blood Disorders, a Division of Regional Cancer Care Associates LLC.

Bethesda, Maryland, United States

University of Michigan

Ann Arbor, Michigan, United States

Park Nicollet

Minneapolis, Minnesota, United States

Washington University School of Medicine

St Louis, Missouri, 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

Stony Brook Cancer Center

Stony Brook, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

East Carolina Health - Beaufort, Inc. DBA Marion L. Shepard Cancer Center

Washington, North Carolina, United States

Oncology Hematology Care

Cincinnati, Ohio, United States

ProMedica Flower Hospital

Sylvania, Ohio, United States

St. Charles Health System, Inc.

Bend, Oregon, United States

Good Samaritan Hospital Corvallis - SHOC

Corvallis, Oregon, United States

St. Luke's University Health Network

Bethlehem, Pennsylvania, United States

Albert Einstein Cancer Center

Philadelphia, Pennsylvania, United States

Charleston Hematology Oncology Associates, PA

Charleston, South Carolina, United States

Bon Secours Saint Francis Cancer Center

Greenville, South Carolina, United States

Texas Oncology

Bedford, Texas, United States

Coastal Bend Cancer Center

Corpus Christi, Texas, United States

Mary Crowley Cancer Research Center

Dallas, Texas, United States

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States

Texas Oncology - Dallas

Dallas, Texas, United States

Texas Oncology - Grapevine

Grapevine, Texas, United States

Millennium Oncology

Houston, Texas, United States

Methodist Richardson Cancer Center

Richardson, Texas, United States

Brooke Army Medical Center

San Antonio, Texas, United States

Scott & White Healthcare

Temple, Texas, United States

Texas Oncology - Longview and Tyler

Tyler, Texas, United States

University of TX Health Science Center at Tyler

Tyler, Texas, United States

Virginia Oncology Associates

Multiple Locations, Virginia, United States

Providence Regional Medical Center Everett, PRCP - Clinical Research

Everett, Washington, United States

SCCA - Evergreen Health

Kirkland, Washington, United States

University of Washington

Multiple Locations, Washington, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

SCCA - Group Health

Seattle, Washington, United States

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Royal Brisbane & Women's Hospital

Herston, Queensland, Australia

Lyell McEwin Hospital

Elizabeth Vale, South Australia, Australia

Royal Hobart Hospital

Hobart, Tasmania, Australia

Western Health - Sunshine Hospital

Saint Albans, Victoria, Australia

Hospital Barmherzige Schwestern Linz

Linz, , Austria

Krankenhaus der Barmherzigen Schwestern Linz

Linz, , Austria

LKH Salzburg 3rd Medical Department with Hematology

Salzburg, , Austria

Klinikum Wels-Grieskirchen GmbH, IV. Internal Department

Wels, , Austria

Grand Hôpital de Charleroi, Grand Rue 3

Charleroi, Hainaut, Belgium

CHU Dinant Godinne UCL Namur

Yvoir, Namur, Belgium

Institut Jules Bordet

Brussels, , Belgium

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Antwerp University Hospital

Edegem, , Belgium

Domaine Universitaire du Sart Tilman

Liège, , Belgium

Masarykův onkologický ústav

Brno, , Czechia

Všeobecné fakultní nemocnice v Praze, Onkologická klinika

Prague, , Czechia

Thomayerova nemocnice, Onkologická klinika 1.LF TN Praha

Prague, , Czechia

Fakultní nemocnice v Motole, Komplexní onkologické centrum

Prague, , Czechia

Semmelweis University 1st Dept. Of Internal Medicine, Oncology Division

Budapest, , Hungary

"B" Dept. Of Internal Medicine, National Institute of Oncology

Budapest, , Hungary

Uzsoki Hospital, Dept. of Oncoradiology

Budapest, , Hungary

Dept. Of Oncology, Somogy County Kaposi Mor Teaching Hospital

Kaposvár, , Hungary

Dept. Of Oncology, Tolna County Balassa Janos Hospital

Szekszárd, , Hungary

Rambam Health Care Campus

Haifa, , Israel

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

FONDAZIONE POLIAMBULANZA â€" ISTITUTO OSPEDALIERO

Brescia, , Italy

A.O. Universitaria Arcispedale S.Anna Di Ferrara

Cona, , Italy

Azienda Ospedaliera University Pisana Uo Oncol Medica 2

Pisa, , Italy

U.O. Oncologia Medica

Pontedera, , Italy

San Giovanni Calibita" Fatebenefratelli Hospital

Rome, , Italy

Academic Medical Centre Amsterdam

Amsterdam, , Netherlands

Amphia Hospital

Breda, , Netherlands

University Medical Center Utrecht Heidelberglaan

Utrecht, , Netherlands

Bialostockie Centrum Onkologii im. Marii Sklodowskiej-Curie w Bialymstoku Odzial Onkologii Klinicznej

Bialystok, , Poland

Regionalne Centrum Onkologii Szpitala im. Prof. Franciszka Łukaszczyka

Bydgoszcz, , Poland

Szpital Wojewodzki w Gdyni Sp. Z o.o., Szpital Morski im PCK

Gdynia, , Poland

Przychodnia Lekarska "Komed"

Konin, , Poland

NZOZ Vesalius

Krakow, , Poland

Samodzielny Publiczny ZOZ MSZ z Warmińsko-Mazurskim Centrum Onkologii w Olsztynie

Olsztyn, , Poland

Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie, Klinika Gastroenterologii Onkologicznej

Warsaw, , Poland

NZOZ Magodent sp z.o.o.

Warsaw, , 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

Institut Català d'Oncologia

Barcelona, , Spain

Hospital ClÃ-nica Benidorm

Benidorm, , Spain

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Hospital 12 De Octubre

Madrid, , Spain

CIOCC, Centro Integral Oncológico Clara Campal

Madrid, , Spain

Hospital Son Llà tzer

Palma, , Spain

Hospital Universitario La Fe, Consultas Externas Oncologia

Valencia, , Spain

Istituto Oncologico della Svizzera Italiania

Bellinzona, , Switzerland

Kantonsspital GraubÃnden

Chur, , Switzerland

Christie Hospital

Manchester, Greater Manchester, United Kingdom

The Royal Marsden Hospital

Sutton, Surrey, United Kingdom

Countries

United States; Australia; Austria; Belgium; Czechia; Hungary; Israel; Italy; Netherlands; Poland; Spain; Switzerland; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 24746841 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2012-PT023

Identifier Type: -

Identifier Source: org_study_id