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

• Sponsor: Janssen Research & Development, LLC (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01767857
• Collaborator: (none)
• Enrollment: 643
• Locations: 113
• Arms: 2
• Actual Duration (Months): 51
• Patients Per Site: 5.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Colorectal Cancer	Drug: Xilonix; Drug: Placebo	Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 643 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Phase III Double-blinded, Placebo Controlled Study of Xilonix™ for Improving Survival in Metastatic Colorectal Cancer
• Actual Study Start Date: Mar 31, 2013
• Actual Primary Completion Date: Jun 30, 2017
• Actual Study Completion Date: Jun 30, 2017

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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.

3. Change From Baseline in Platelet Counts [Baseline and Week 8]

   Change from baseline in platelet counts up to Week 8 was evaluated.

4. 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.

5. 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.

6. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

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

Sponsors and Collaborators

• Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

• Study Protocol - Jun 5, 2017
• Statistical Analysis Plan - Aug 18, 2017

More Information

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-1α 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.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT01767857
• Other Study ID Numbers: 2012-PT023
• First Posted: Jan 14, 2013
• Last Update Posted: Jun 29, 2021
• Last Verified: Jun 1, 2021

• Keywords provided by Janssen Research & Development, LLC: Pivotal; Colorectal; Survival; Phase 3
• Additional relevant MeSH terms: Colorectal Neoplasms

Study Results

Participant Flow

Pre-assignment Detail	Total 643 participants were screened and enrolled in the study. Out of them, only 611 participants have received the study drug and participated in the study while 32 participants never received any study drug.

Arm/Group Title	Xilonix	Placebo
Arm/Group Description	Participants received 7.5 milligram per kilogram (mg/kg) Xilonix (MABp1) via intravenous (IV) injection once every 2 weeks until evidence of radiographic or clinical progression along with best supportive care (BSC) (up to 18 months).	Participants received placebo via IV injection once every 2 weeks until evidence of radiographic or clinical progression plus BSC (up to 18 months).
Period Title: Overall Study
STARTED	430	213
Treated	411	200
COMPLETED	0	0
NOT COMPLETED	430	213

Baseline Characteristics

Arm/Group Title	Xilonix	Placebo	Total
Arm/Group Description	Participants received 7.5 milligram per kilogram (mg/kg) Xilonix (MABp1) via intravenous (IV) injection once every 2 weeks until evidence of radiographic or clinical progression along with best supportive care (BSC) (up to 18 months).	Participants received placebo via IV injection once every 2 weeks until evidence of radiographic or clinical progression plus BSC (up to 18 months).	Total of all reporting groups
Overall Participants	411	200	611
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.9 (10.14)	61.1 (9.98)	62.3 (10.11)
Sex: Female, Male (Count of Participants)
Female	159 38.7%	94 47%	253 41.4%
Male	252 61.3%	106 53%	358 58.6%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	15 3.6%	2 1%	17 2.8%
Black or African American	20 4.9%	8 4%	28 4.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
White	355 86.4%	186 93%	541 88.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Other	21 5.1%	4 2%	25 4.1%
Region of Enrollment (Count of Participants)
Australia	18 4.4%	7 3.5%	25 4.1%
Austria	12 2.9%	3 1.5%	15 2.5%
Belgium	49 11.9%	27 13.5%	76 12.4%
Czech Republic	8 1.9%	3 1.5%	11 1.8%
England	7 1.7%	3 1.5%	10 1.6%
Hungary	8 1.9%	3 1.5%	11 1.8%
Israel	4 1%	3 1.5%	7 1.1%
Italy	11 2.7%	7 3.5%	18 2.9%
Netherlands	8 1.9%	4 2%	12 2%
Poland	30 7.3%	18 9%	48 7.9%
Spain	118 28.7%	55 27.5%	173 28.3%
Switzerland	3 0.7%	3 1.5%	6 1%
USA	135 32.8%	64 32%	199 32.6%
Age (years) (Count of Participants)
< 65 years	229 55.7%	122 61%	351 57.4%
Between 65 and 75 years	141 34.3%	64 32%	205 33.6%
> 75 years	41 10%	14 7%	55 9%
Missing	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population included all participants who were randomized and received at least one infusion of study drug.

Arm/Group Title	Xilonix	Placebo
Arm/Group Description	Participants received 7.5 milligram per kilogram (mg/kg) Xilonix (MABp1) via intravenous (IV) injection once every 2 weeks until evidence of radiographic or clinical progression along with best supportive care (BSC) (up to 18 months).	Participants received placebo via IV injection once every 2 weeks until evidence of radiographic or clinical progression plus BSC (up to 18 months).
Measure Participants	411	200
Median (95% Confidence Interval) [Months]	5.6	5.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Xilonix, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.613
	Comments
	Method	Log Rank
	Comments

2. Secondary Outcome

Title	Change From Baseline in Lean Body Mass (LBM) Measured by Dual-energy X-ray Absorptiometry (DEXA) Scans
Description	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.
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

The per protocol (PP) population was defined as participants that had baseline and follow up values for both the DEXA assessment and the European Organization for Research and Treatment of Cancer (EORTC) questionnaire.

Arm/Group Title	Xilonix	Placebo
Arm/Group Description	Participants received 7.5 mg/kg Xilonix (MABp1) via IV injection once every 2 weeks until evidence of radiographic or clinical progression along with BSC (up to 18 months).	Participants received placebo via IV injection once every 2 weeks until evidence of radiographic or clinical progression plus BSC (up to 18 months).
Measure Participants	202	94
Least Squares Mean (Standard Error) [kilogram (kg)]	0.51 (0.158)	-0.21 (0.231)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Xilonix, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.011
	Comments
	Method	ANCOVA
	Comments

3. Secondary Outcome

Title	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)
Description	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.
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

The PP population was defined as participants that had baseline and follow up values for both the DEXA assessment and the EORTC questionnaire.

Arm/Group Title	Xilonix	Placebo
Arm/Group Description	Participants received 7.5 mg/kg Xilonix (MABp1) via IV injection once every 2 weeks until evidence of radiographic or clinical progression along with BSC (up to 18 months).	Participants received placebo via IV injection once every 2 weeks until evidence of radiographic or clinical progression plus BSC (up to 18 months).
Measure Participants	202	94
Global Health Status/Qol	-6.64 (1.392)	-8.16 (2.041)
Pain	8.50 (1.707)	10.27 (2.503)
Fatigue	7.42 (1.516)	8.82 (2.223)
Appetite Loss	9.34 (2.010)	11.84 (2.947)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Xilonix, Placebo
	Comments	Statistical Analysis for Global Health Status/Qol
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.541
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Xilonix, Placebo
	Comments	Statistical Analysis for Pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.560
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Xilonix, Placebo
	Comments	Statistical Analysis for Fatigue
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.603
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Xilonix, Placebo
	Comments	Statistical Analysis for Appetite Loss
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.485
	Comments
	Method	ANCOVA
	Comments

4. Secondary Outcome

Title	Change From Baseline in Platelet Counts
Description	Change from baseline in platelet counts up to Week 8 was evaluated.
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

The PP population was defined as participants that had baseline and follow up values for both the DEXA assessment and the EORTC questionnaire.

Arm/Group Title	Xilonix	Placebo
Arm/Group Description	Participants received 7.5 mg/kg Xilonix (MABp1) via IV injection once every 2 weeks until evidence of radiographic or clinical progression along with BSC (up to 18 months).	Participants received placebo via IV injection once every 2 weeks until evidence of radiographic or clinical progression plus BSC (up to 18 months).
Measure Participants	202	94
Least Squares Mean (Standard Error) [1000 cells/cubic millimeter]	5.50 (4.721)	16.19 (7.082)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Xilonix, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.210
	Comments
	Method	ANCOVA
	Comments

5. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	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.
Time Frame	Up to 18 Months

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population consisted of all randomized participants.

Arm/Group Title	Xilonix	Placebo
Arm/Group Description	Participants received 7.5 mg/kg Xilonix (MABp1) via IV injection once every 2 weeks until evidence of radiographic or clinical progression along with BSC (up to 18 months).	Participants received placebo via IV injection once every 2 weeks until evidence of radiographic or clinical progression plus BSC (up to 18 months).
Measure Participants	430	213
Median (95% Confidence Interval) [Months]	2.1	2.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Xilonix, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.768
	Comments
	Method	Log Rank
	Comments

6. Secondary Outcome

Title	Percentage of Participants With Objective Response (OR)
Description	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.
Time Frame	Up to 18 months

Outcome Measure Data

Analysis Population Description

The mITT population included all participants who were randomized and received at least one infusion of study drug.

Arm/Group Title	Xilonix	Placebo
Arm/Group Description	Participants received 7.5 mg/kg Xilonix (MABp1) via IV injection once every 2 weeks until evidence of radiographic or clinical progression along with BSC (up to 18 months).	Participants received placebo via IV injection once every 2 weeks until evidence of radiographic or clinical progression plus BSC (up to 18 months).
Measure Participants	411	200
Number [Percentage of Participants]	0 0%	0 0%

7. Secondary Outcome

Title	Percentage of Participants With Disease Control
Description	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).
Time Frame	Up to 18 months

Outcome Measure Data

Analysis Population Description

The participants with baseline and follow up radiographic assessments were included in this analysis.

Arm/Group Title	Xilonix	Placebo
Arm/Group Description	Participants received 7.5 mg/kg Xilonix (MABp1) via IV injection once every 2 weeks until evidence of radiographic or clinical progression along with BSC (up to 18 months).	Participants received placebo via IV injection once every 2 weeks until evidence of radiographic or clinical progression plus BSC (up to 18 months).
Measure Participants	296	154
Number [Percentage of Participants]	25 6.1%	27.3 13.7%

Adverse Events

Time Frame	Up to 18 months
Adverse Event Reporting Description	Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.
Arm/Group Title	Xilonix		Placebo
Arm/Group Description	Participants received 7.5 milligram per kilogram (mg/kg) Xilonix (MABp1) via intravenous (IV) injection once every 2 weeks until evidence of radiographic or clinical progression along with best supportive care (BSC) (up to 18 months).		Participants received placebo via IV injection once every 2 weeks until evidence of radiographic or clinical progression plus BSC (up to 18 months).
All Cause Mortality
	Xilonix		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/411 (6.8%)		13/200 (6.5%)
Serious Adverse Events
	Xilonix		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	169/411 (41.1%)		84/200 (42%)
Blood and lymphatic system disorders
Anaemia	3/411 (0.7%)		5/200 (2.5%)
Thrombocytopenia	1/411 (0.2%)		0/200 (0%)
Cardiac disorders
Atrial Fibrillation	1/411 (0.2%)		1/200 (0.5%)
Pericardial Effusion	1/411 (0.2%)		0/200 (0%)
Ear and labyrinth disorders
Vertigo	1/411 (0.2%)		0/200 (0%)
Gastrointestinal disorders
Abdominal Pain	9/411 (2.2%)		6/200 (3%)
Anorectal Stenosis	0/411 (0%)		1/200 (0.5%)
Ascites	7/411 (1.7%)		0/200 (0%)
Constipation	2/411 (0.5%)		0/200 (0%)
Diarrhoea	2/411 (0.5%)		1/200 (0.5%)
Dysphagia	1/411 (0.2%)		0/200 (0%)
Gastric Haemorrhage	1/411 (0.2%)		0/200 (0%)
Gastrointestinal Perforation	1/411 (0.2%)		0/200 (0%)
Haematemesis	1/411 (0.2%)		0/200 (0%)
Ileus	2/411 (0.5%)		2/200 (1%)
Intestinal Obstruction	2/411 (0.5%)		2/200 (1%)
Large Intestinal Obstruction	3/411 (0.7%)		0/200 (0%)
Large Intestine Perforation	1/411 (0.2%)		1/200 (0.5%)
Lower Gastrointestinal Haemorrhage	1/411 (0.2%)		0/200 (0%)
Malignant Bowel Obstruction	1/411 (0.2%)		0/200 (0%)
Nausea	2/411 (0.5%)		3/200 (1.5%)
Oesophageal Haemorrhage	1/411 (0.2%)		0/200 (0%)
Oesophageal Varices Haemorrhage	1/411 (0.2%)		1/200 (0.5%)
Rectal Haemorrhage	0/411 (0%)		1/200 (0.5%)
Rectal Stenosis	0/411 (0%)		1/200 (0.5%)
Small Intestinal Haemorrhage	1/411 (0.2%)		0/200 (0%)
Small Intestinal Obstruction	6/411 (1.5%)		1/200 (0.5%)
Subileus	0/411 (0%)		1/200 (0.5%)
Upper Gastrointestinal Haemorrhage	1/411 (0.2%)		0/200 (0%)
Vomiting	2/411 (0.5%)		2/200 (1%)
General disorders
Adverse Drug Reaction	1/411 (0.2%)		0/200 (0%)
Asthenia	3/411 (0.7%)		2/200 (1%)
Chest Pain	2/411 (0.5%)		0/200 (0%)
Death	3/411 (0.7%)		1/200 (0.5%)
Disease Progression	21/411 (5.1%)		14/200 (7%)
Fatigue	0/411 (0%)		1/200 (0.5%)
General Physical Health Deterioration	8/411 (1.9%)		5/200 (2.5%)
Localised Oedema	1/411 (0.2%)		0/200 (0%)
Malaise	1/411 (0.2%)		1/200 (0.5%)
Oedema Peripheral	3/411 (0.7%)		0/200 (0%)
Pain	5/411 (1.2%)		0/200 (0%)
Performance Status Decreased	1/411 (0.2%)		0/200 (0%)
Pyrexia	6/411 (1.5%)		1/200 (0.5%)
Hepatobiliary disorders
Bile Duct Obstruction	2/411 (0.5%)		0/200 (0%)
Bile Duct Stenosis	2/411 (0.5%)		0/200 (0%)
Cholangitis	2/411 (0.5%)		0/200 (0%)
Cholestasis	0/411 (0%)		1/200 (0.5%)
Hepatic Failure	11/411 (2.7%)		3/200 (1.5%)
Hyperbilirubinaemia	1/411 (0.2%)		2/200 (1%)
Hypertransaminasaemia	1/411 (0.2%)		0/200 (0%)
Jaundice	1/411 (0.2%)		0/200 (0%)
Jaundice Cholestatic	2/411 (0.5%)		0/200 (0%)
Liver Disorder	0/411 (0%)		1/200 (0.5%)
Infections and infestations
Abdominal Abscess	2/411 (0.5%)		0/200 (0%)
Catheter Site Abscess	0/411 (0%)		1/200 (0.5%)
Catheter Site Infection	1/411 (0.2%)		0/200 (0%)
Gastroenteritis	0/411 (0%)		1/200 (0.5%)
Infection	1/411 (0.2%)		1/200 (0.5%)
Kidney Infection	2/411 (0.5%)		0/200 (0%)
Osteomyelitis	1/411 (0.2%)		0/200 (0%)
Pneumonia	5/411 (1.2%)		2/200 (1%)
Pneumonia Staphylococcal	0/411 (0%)		1/200 (0.5%)
Respiratory Tract Infection	2/411 (0.5%)		1/200 (0.5%)
Sepsis	3/411 (0.7%)		4/200 (2%)
Septic Shock	1/411 (0.2%)		0/200 (0%)
Skin Infection	0/411 (0%)		1/200 (0.5%)
Thrombophlebitis Septic	0/411 (0%)		1/200 (0.5%)
Upper Respiratory Tract Infection	1/411 (0.2%)		1/200 (0.5%)
Urinary Tract Infection	2/411 (0.5%)		0/200 (0%)
Viral Infection	1/411 (0.2%)		0/200 (0%)
Injury, poisoning and procedural complications
Fall	1/411 (0.2%)		0/200 (0%)
Femur Fracture	1/411 (0.2%)		0/200 (0%)
Gastrointestinal Stoma Complication	3/411 (0.7%)		2/200 (1%)
Infusion Related Reaction	1/411 (0.2%)		0/200 (0%)
Spinal Compression Fracture	0/411 (0%)		2/200 (1%)
Stoma Site Haemorrhage	1/411 (0.2%)		1/200 (0.5%)
Thoracic Vertebral Fracture	1/411 (0.2%)		0/200 (0%)
Toxicity to Various Agents	1/411 (0.2%)		0/200 (0%)
Urinary Tract Stoma Complication	0/411 (0%)		1/200 (0.5%)
Urostomy Complication	1/411 (0.2%)		1/200 (0.5%)
Investigations
Alanine Aminotransferase Increased	1/411 (0.2%)		0/200 (0%)
Blood Bilirubin Increased	1/411 (0.2%)		2/200 (1%)
Blood Culture Positive	0/411 (0%)		1/200 (0.5%)
Gamma-Glutamyltransferase Increased	0/411 (0%)		1/200 (0.5%)
Metabolism and nutrition disorders
Dehydration	0/411 (0%)		1/200 (0.5%)
Failure to Thrive	1/411 (0.2%)		0/200 (0%)
Hyperglycaemia	1/411 (0.2%)		0/200 (0%)
Hypernatraemia	1/411 (0.2%)		0/200 (0%)
Hypoglycaemia	1/411 (0.2%)		0/200 (0%)
Hypokalaemia	1/411 (0.2%)		0/200 (0%)
Musculoskeletal and connective tissue disorders
Back Pain	2/411 (0.5%)		0/200 (0%)
Bone Pain	2/411 (0.5%)		0/200 (0%)
Intervertebral Disc Protrusion	1/411 (0.2%)		0/200 (0%)
Musculoskeletal Pain	2/411 (0.5%)		0/200 (0%)
Pain in Extremity	2/411 (0.5%)		0/200 (0%)
Spinal Pain	0/411 (0%)		1/200 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bone Neoplasm	0/411 (0%)		1/200 (0.5%)
Cancer Pain	1/411 (0.2%)		0/200 (0%)
Colon Cancer	1/411 (0.2%)		0/200 (0%)
Colorectal Cancer	8/411 (1.9%)		5/200 (2.5%)
Colorectal Cancer Metastatic	0/411 (0%)		1/200 (0.5%)
Malignant Neoplasm Progression	1/411 (0.2%)		1/200 (0.5%)
Malignant Pleural Effusion	1/411 (0.2%)		0/200 (0%)
Metastases to Central Nervous System	3/411 (0.7%)		4/200 (2%)
Neoplasm Progression	3/411 (0.7%)		2/200 (1%)
Pelvic Neoplasm	1/411 (0.2%)		0/200 (0%)
Nervous system disorders
Aphasia	1/411 (0.2%)		0/200 (0%)
Balance Disorder	0/411 (0%)		1/200 (0.5%)
Brain Oedema	1/411 (0.2%)		0/200 (0%)
Loss of Consciousness	1/411 (0.2%)		0/200 (0%)
Neuralgia	1/411 (0.2%)		0/200 (0%)
Seizure	2/411 (0.5%)		0/200 (0%)
Spinal Cord Compression	0/411 (0%)		1/200 (0.5%)
Syncope	1/411 (0.2%)		0/200 (0%)
Psychiatric disorders
Completed Suicide	1/411 (0.2%)		0/200 (0%)
Confusional State	1/411 (0.2%)		0/200 (0%)
Renal and urinary disorders
Acute Kidney Injury	8/411 (1.9%)		1/200 (0.5%)
Haematuria	3/411 (0.7%)		0/200 (0%)
Hydronephrosis	2/411 (0.5%)		1/200 (0.5%)
Nephrolithiasis	0/411 (0%)		1/200 (0.5%)
Renal Failure	2/411 (0.5%)		0/200 (0%)
Urinary Incontinence	1/411 (0.2%)		0/200 (0%)
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress Syndrome	2/411 (0.5%)		0/200 (0%)
Acute Respiratory Failure	1/411 (0.2%)		0/200 (0%)
Chronic Obstructive Pulmonary Disease	3/411 (0.7%)		0/200 (0%)
Dyspnoea	12/411 (2.9%)		9/200 (4.5%)
Epistaxis	1/411 (0.2%)		0/200 (0%)
Haemoptysis	0/411 (0%)		1/200 (0.5%)
Pleural Effusion	5/411 (1.2%)		2/200 (1%)
Pneumonitis	1/411 (0.2%)		1/200 (0.5%)
Pneumothorax	0/411 (0%)		1/200 (0.5%)
Pulmonary Embolism	1/411 (0.2%)		2/200 (1%)
Respiratory Failure	3/411 (0.7%)		0/200 (0%)
Surgical and medical procedures
Pain Management	1/411 (0.2%)		0/200 (0%)
Ureteral Stent Removal	1/411 (0.2%)		0/200 (0%)
Vascular disorders
Circulatory Collapse	1/411 (0.2%)		0/200 (0%)
Deep Vein Thrombosis	0/411 (0%)		1/200 (0.5%)
Other (Not Including Serious) Adverse Events
	Xilonix		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	324/411 (78.8%)		167/200 (83.5%)
Blood and lymphatic system disorders
Anaemia	42/411 (10.2%)		20/200 (10%)
Cardiac disorders
Sinus Tachycardia	11/411 (2.7%)		10/200 (5%)
Gastrointestinal disorders
Abdominal Pain	78/411 (19%)		41/200 (20.5%)
Constipation	51/411 (12.4%)		31/200 (15.5%)
Diarrhoea	45/411 (10.9%)		22/200 (11%)
Nausea	79/411 (19.2%)		46/200 (23%)
Vomiting	46/411 (11.2%)		20/200 (10%)
General disorders
Asthenia	63/411 (15.3%)		35/200 (17.5%)
Fatigue	109/411 (26.5%)		60/200 (30%)
Oedema Peripheral	39/411 (9.5%)		23/200 (11.5%)
Pyrexia	38/411 (9.2%)		27/200 (13.5%)
Investigations
Aspartate Aminotransferase Increased	23/411 (5.6%)		6/200 (3%)
Blood Alkaline Phosphatase Increased	20/411 (4.9%)		13/200 (6.5%)
Blood Bilirubin Increased	25/411 (6.1%)		7/200 (3.5%)
Metabolism and nutrition disorders
Decreased Appetite	84/411 (20.4%)		51/200 (25.5%)
Musculoskeletal and connective tissue disorders
Back Pain	44/411 (10.7%)		27/200 (13.5%)
Nervous system disorders
Headache	21/411 (5.1%)		13/200 (6.5%)
Psychiatric disorders
Insomnia	16/411 (3.9%)		10/200 (5%)
Renal and urinary disorders
Proteinuria	11/411 (2.7%)		11/200 (5.5%)
Respiratory, thoracic and mediastinal disorders
Cough	40/411 (9.7%)		27/200 (13.5%)
Dyspnoea	49/411 (11.9%)		27/200 (13.5%)
Vascular disorders
Hypertension	25/411 (6.1%)		15/200 (7.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.