A Study Evaluating Xilonix™ in Symptomatic Colorectal Cancer Patients Refractory To Standard Therapy

• Register: EUCTR
• Last refreshed on: 9 October 2017
• Main ID: EUCTR2014-000550-12-HU
• Date of registration: 17/04/2014
• Prospective Registration: Yes
• Primary sponsor: XBiotech Germany GmbH
• Public title: A Study Evaluating Xilonix™ in Symptomatic Colorectal Cancer Patients Refractory To Standard Therapy
• Scientific title: A Double Blind, Placebo Controlled, Pivotal Phase III Study Evaluating Xilonix™ in Symptomatic Colorectal Cancer Patients Refractory To Standard Therapy
• Date of first enrolment: 23/07/2014
• Target sample size: 276
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-000550-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Bulgaria, Czech Republic, France, Georgia, Germany, Hungary, Poland, Russian Federation, United Kingdom

Contacts

• Name: Clinical Trial Information
• Affiliation: XBiotech USA, Inc.

• Name: Clinical Trial Information
• Affiliation: XBiotech USA, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects are included in the study if they meet all of the following 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 failed both an oxaliplatin (oxaliplatin may have been in the adjuvant setting) and an irinotecan based regimen.
2. Symptomatic Disease: One symptom from each domain (metabolic and functional) must be present.
• Evidence of metabolic dysfunction, defined as the presence of one or more of the following:
• Any degree (up to 20%) of unintentional total body weight loss in the previous 6 months
• Serum Interleukin 6 levels =10 pg/ml
• Evidence of reduced function or presence of cancer related symptoms as determined by EORTC QLQ-C30.
• Appetite reduction, with a score of >10
• Presence of fatigue, with a score of >10
• Presence of Pain, with a score of >10
• Decreased Role, Emotional and Social function, with a score of < 90.
3. Eastern Cooperative Oncology Group (ECOG) performance status 1 or 2.
4. In the Investigator’s judgment, a life expectancy of at least three (3) months.
5. In the Investigator’s judgement, patients should not need corticosteroids during the 8 week assessment period.
6. At least 2 weeks since the last previous cancer treatment including: chemotherapy, radiation therapy, immunotherapy, surgery, hormonal therapy, or targeted biologics and 4 weeks for patients who received treatment immediately prior to the study with anti-IL-1 or anti-TNF agents.
7. For those subjects who have previously received treatment for cancer related fatigue with agents such as corticosteroids or stimulants, a 2 week washout period is required from the last dose to C1D1.
8. Age =18, male or female subjects.
9. Serum potassium and magnesium levels within central laboratory normal limits. Total serum calcium or ionized calcium level must be greater than or equal to the lower limit of normal. Subjects with low potassium, calcium and magnesium levels may be replenished to allow for protocol entry.
10. Adequate renal function, defined by serum creatinine = 1.5 x ULN.
11. Adequate hepatic function defined as:
§ total bilirubin = 1.5 times the central lab ULN.
§ alanine aminotransferase (ALT) = 2.0 times the central lab ULN.
Exception: subjects with known liver metastases: = 3.0 times the central lab ULN for ALT.
12. Adequate bone marrow function as defined as:
§ absolute neutrophil count (neutrophil and bands) of = 1,500/mm3 (= 1.5 x 109/L)
§ platelet count between 150,000/mm3 and 450,000/mm3
§ hemoglobin of = 9 g/dL
13. For women of childbearing potential (WOCBP), a negative serum pregnancy test result at Screening.
14. Signed and dated institutional review board (IRB)/ Ethics Committee (EC)-approved informed consent before any protocol-specific screening procedures are performer.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 166
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 110

Exclusion criteria:
Subjects with ANY of the following will be excluded from the study:
1. Mechanical obstruction that would prevent adequate oral nutritional intake.
2. >20% total body weight loss in the previous 6 months.
3. Serious uncontrolled medical disorder, or active infection, that would impair the ability of the patient to receive protocol therapy.
4. Uncontrolled or significant cardiovascular disease, including:
• A myocardial infarction within the past 6 months.
• Uncontrolled angina within the past 3 months.
• Congestive heart failure within the past 3 months, if defined as NYHC-II.
• Diagnosed or suspected congenital long QT syndrome.
• Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, Wolff-Parkinson-White (WPW) syndrome, or torsade de pointes).
• Any history of second or third degree heart block (may be eligible if currently have a pacemaker).
• Uncontrolled hypertension (blood pressure >150 mm Hg systolic and >95 mm Hg diastolic).
5. Dementia or altered mental status that would prohibit the understanding or rendering of informed consent.
6. 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.
7. Subjects who have received extensive prior radiation therapy to the bone marrow. Extensive radiation therapy is defined as treatment of more than one axial bony metastasis. However for subjects with rectal cancer pelvic irradiation, in addition to treatment of one axial bony metastasis, is acceptable.
8. Immunocompromised subjects, including subjects known to be infected with human immunodeficiency virus (HIV).
9. Known hepatitis B surface antigen and/or positive hepatitis C antibody or known history of infection.
10. History of tuberculosis (latent or active) or positive Interferon-gamma release assay (IGRA).
11. Receipt of a live (attenuated) vaccine within 1 month prior to Randomization
12. Subjects with history of hypersensitivity to compounds of similar chemical or biologic composition to Xilonix™ or any component of its formulations.
13. Women who are pregnant or breastfeeding.
14. 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 randomization, for the duration of the study, and for at least 3 months after the last dose of study medication.
15.History of progressive multifocal leukoencephalopathy or other demyelinating disease.
16.Subjects on immunosuppressive therapy, including transplant patients.
17. Subjects with known brain metastases. Subjects with symptoms of brain metastases during screening should undergo CT imaging prior to randomization.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Symptomatic Colorectal Cancer
MedDRA version: 17.1 Level: PT Classification code 10061451 Term: Colorectal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: XILONIX™
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: N/A
Current Sponsor code: XILONIX
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 8

Secondary Objective: Secondary Endpoints:
• Secondary efficacy endpoints include measures of key cancer symptoms, as well as pharmacodynamics parameters. Parameters to be measured are: (1) change in functional scales and (2) global QoL as assessed by the EORTC QLQ-C30 questionnaire at screening and 8 week follow-up; (3) reduction in serum IL-6; and (4) stabilization of platelet count at 8 week compared to screening.
• Safety and tolerability of Xilonix™ as compared to placebo control.

Main Objective: Primary Efficacy Endpoint:
• The primary endpoint of this study will be the objective response rate (ORR), a composite measure consisting of change in lean body mass (LBM) and change in quality of life, from screening to week 8. The ORR will be defined as a stabilization or positive (=0 kg) change in lean body mass (LBM)—as assessed by dual-energy X-ray absorptiometry (DEXA) scan, and improvement or no worsening (=0 score point change) on any two of the three symptom scale measures (fatigue, pain, appetite) of EORTC QLQ-C30.

Primary end point(s): The primary endpoint of this study will be the objective response rate (ORR), a composite measure consisting of change in lean body mass (LBM) and change in quality of life, from screening to week 8. The ORR will be defined as a stabilization or positive (=0 kg) change in lean body mass (LBM)—as assessed by dual-energy X-ray absorptiometry (DEXA) scan, and improvement or no worsening (=0 score point change) on any two of the three symptom scale measures (fatigue, pain, appetite) of EORTC QLQ-C30.

Secondary Outcome(s)

Secondary end point(s): Secondary efficacy endpoints include measures of key cancer symptoms, as well as pharmacodynamics parameters. Parameters to be measured are: (1) change in functional scales and (2) global QoL as assessed by the EORTC QLQ-C30 questionnaire at screening and 8 week follow-up; (3) reduction in serum IL-6; and (4) stabilization of platelet count at 8 week compared to screening.
• Safety and tolerability of Xilonix™ as compared to placebo control.

Timepoint(s) of evaluation of this end point: Week 8

Secondary ID(s)

2014-PT026

Source(s) of Monetary Support

XBiotech Germany GmbH