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

Metastatic Colorectal Cancer Clinical Trial

— XCITE  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01767857
• Other study ID #: 2012-PT023
• Status: Terminated
• Phase: Phase 3
• Start date: March 31, 2013
• Est. completion date: June 30, 2017

Study information

• Verified date: June 2021
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 643
• Est. completion date: June 30, 2017
• Est. primary completion date: June 30, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

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

Locations

Country	Name	City	State
Australia	Lyell McEwin Hospital	Elizabeth Vale	South Australia
Australia	Royal Brisbane & Women's Hospital	Herston	Queensland
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Western Health - Sunshine Hospital	Saint Albans	Victoria
Australia	Royal North Shore Hospital	St Leonards	New South Wales
Austria	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
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Institut Jules Bordet	Brussels
Belgium	Grand Hôpital de Charleroi, Grand Rue 3	Charleroi	Hainaut
Belgium	Antwerp University Hospital	Edegem
Belgium	Domaine Universitaire du Sart Tilman	Liège
Belgium	CHU Dinant Godinne UCL Namur	Yvoir	Namur
Czechia	Masarykuv onkologický ústav	Brno
Czechia	Fakultní nemocnice v Motole, Komplexní onkologické centrum	Praha
Czechia	Thomayerova nemocnice, Onkologická klinika 1.LF TN Praha	Praha
Czechia	Všeobecné fakultní nemocnice v Praze, Onkologická klinika	Praha
Hungary	"B" Dept. Of Internal Medicine, National Institute of Oncology	Budapest
Hungary	Semmelweis University 1st Dept. Of Internal Medicine, Oncology Division	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
Israel	Rambam Health Care Campus	Haifa
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	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
Netherlands	Academic Medical Centre Amsterdam	Amsterdam
Netherlands	Amphia Hospital	Breda
Netherlands	University Medical Center Utrecht Heidelberglaan	Utrecht
Poland	Bialostockie Centrum Onkologii im. Marii Sklodowskiej-Curie w Bialymstoku Odzial Onkologii Klinicznej	Bialystok
Poland	Regionalne Centrum Onkologii Szpitala im. Prof. Franciszka Lukaszczyka	Bydgoszcz
Poland	Szpital Wojewodzki w Gdyni Sp. Z o.o., Szpital Morski im PCK	Gdynia
Poland	Przychodnia Lekarska "Komed"	Konin
Poland	NZOZ Vesalius	Kraków
Poland	Samodzielny Publiczny ZOZ MSZ z Warminsko-Mazurskim Centrum Onkologii w Olsztynie	Olsztyn
Poland	Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie, Klinika Gastroenterologii Onkologicznej	Warszawa
Poland	NZOZ Magodent sp z.o.o.	Warszawa
Spain	Hospital Vall Dhebron Edificio Principal Planta Baja	Barcelona
Spain	Institut Català d'Oncologia	Barcelona
Spain	Institut Català d'Oncologia, Hospital Duran i Reynals	Barcelona
Spain	Instituto Oncológico Dr. Rosell.	Barcelona
Spain	Hospital ClÃ-nica Benidorm	Benidorm
Spain	CIOCC, Centro Integral Oncológico Clara Campal	Madrid
Spain	Hospital 12 De Octubre	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Son Llà tzer	Palma
Spain	Hospital Universitario La Fe, Consultas Externas Oncologia	Valencia
Switzerland	Istituto Oncologico della Svizzera Italiania	Bellinzona
Switzerland	Kantonsspital GraubÃnden	Chur
United Kingdom	Christie Hospital	Manchester	Greater Manchester
United Kingdom	The Royal Marsden Hospital	Sutton	Surrey
United States	Pacific Cancer Medical Center, Inc.	Anaheim	California
United States	University of Michigan	Ann Arbor	Michigan
United States	Texas Oncology	Bedford	Texas
United States	St. Charles Health System, Inc.	Bend	Oregon
United States	The Center for Cancer and Blood Disorders, a Division of Regional Cancer Care Associates LLC.	Bethesda	Maryland
United States	St. Luke's University Health Network	Bethlehem	Pennsylvania
United States	Alabama Oncology, Bruno Cancer Center	Birmingham	Alabama
United States	Montefiore Medical Center	Bronx	New York
United States	Charleston Hematology Oncology Associates, PA	Charleston	South Carolina
United States	Swedish Covenant Hospital via Clintell, Inc.	Chicago	Illinois
United States	Oncology Hematology Care	Cincinnati	Ohio
United States	Coastal Bend Cancer Center	Corpus Christi	Texas
United States	Good Samaritan Hospital Corvallis - SHOC	Corvallis	Oregon
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	North Shore Hematology Oncology Associates, PC	East Setauket	New York
United States	Providence Regional Medical Center Everett, PRCP - Clinical Research	Everett	Washington
United States	California Cancer Associates for Research and Excellence, Inc. (cCARE)	Fresno	California
United States	St. Jude Medical Center	Fullerton	California
United States	Texas Oncology - Grapevine	Grapevine	Texas
United States	Bon Secours Saint Francis Cancer Center	Greenville	South Carolina
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Hines VA Hospital	Hines	Illinois
United States	Millennium Oncology	Houston	Texas
United States	Hutchinson Clinic, P.A.	Hutchinson	Kansas
United States	Franciscan St. Francis Health	Indianapolis	Indiana
United States	SCCA - Evergreen Health	Kirkland	Washington
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	James Graham Brown Cancer Center	Louisville	Kentucky
United States	Advanced Medical Specialists	Miami	Florida
United States	Park Nicollet	Minneapolis	Minnesota
United States	Southern Cancer Center, PC	Mobile	Alabama
United States	Northern Westchester Hospital	Mount Kisco	New York
United States	University of Washington	Multiple Locations	Washington
United States	Virginia Oncology Associates	Multiple Locations	Virginia
United States	Northwest Alabama Cancer Center, PC	Muscle Shoals	Alabama
United States	Weill Cornell Medical College	New York	New York
United States	Ventura County Hematology-Oncology Specialists	Oxnard	California
United States	Stanford Cancer Institute	Palo Alto	California
United States	Oncology Specialists, SC	Park Ridge	Illinois
United States	Albert Einstein Cancer Center	Philadelphia	Pennsylvania
United States	Methodist Richardson Cancer Center	Richardson	Texas
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Brooke Army Medical Center	San Antonio	Texas
United States	SCCA - Group Health	Seattle	Washington
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Stony Brook Cancer Center	Stony Brook	New York
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	Scott & White Healthcare	Temple	Texas
United States	Lewis Hall Singletary Oncology Center	Thomasville	Georgia
United States	Arizona Oncology Associates	Tucson	Arizona
United States	Texas Oncology - Longview and Tyler	Tyler	Texas
United States	University of TX Health Science Center at Tyler	Tyler	Texas
United States	East Carolina Health - Beaufort, Inc. DBA Marion L. Shepard Cancer Center	Washington	North Carolina
United States	American Institute of Research	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

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

References & Publications (1)

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-1a 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Change From Baseline in Platelet Counts	Change from baseline in platelet counts up to Week 8 was evaluated.	Baseline and Week 8
Secondary	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
Secondary	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
Secondary	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