Phase III Double-blinded, Placebo Controlled Study of Xilonix* for Improving Survival in Metastatic Colorectal Cancer
- Conditions
- Metastatic Colorectal Cancer - Cancer of the colon or the rectum that has spread10017990
- Registration Number
- NL-OMON45233
- Lead Sponsor
- XBiotech Germany GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 12
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 experienced progression (or intolerance) after treatment with at least all of the following agents: oxaliplatin, irinotecan, flouropyrimidine, 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 and 4 weeks for patients who received treatment immediately prior to the study with anti-IL-1 or anti-TNF agents.
5. Age * 18 years, male or female subjects.
6. Serum potassium and magnesium levels within Central Lab 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.
7. Adequate renal function, defined by serum creatinine * 1.5 x Central Lab ULN.
8. 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.
9. Adequate bone marrow function as defined as:
* absolute neutrophil count (neutrophil and bands) of * 1,500/mm3 (* 1.5 x 109/L)
* platelet count of * 100,000/mm3 (* 100 x109/L)
* hemoglobin of * 9 g/dL
10. For women of childbearing potential (WOCBP), a negative serum pregnancy test result at Screening and monthly thereafter.;For women who are not postmenopausal (24 months of amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to use adequate methods of contraception, during the treatment period and for at least 1 month after the last dose of study drug.
Acceptable contraceptive measures include:
- Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: Oral, Intravaginal or transdermal
- Progestogen-only hormonal contraception associated with inhibition of ovulation; Oral, injectable or implantable
- Intrauterine device (IUD)
- Intrauterine hormone-releasing system (IUS)
- Barrier or sterilization methods such as condoms, bilateral tubal occlusion, vasectomized partner or sexual abstinence ;For men: agreement to use a barrier method of contraception during the treatment period and for at least 1 month after the last dose of study drug
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.
Subjects with ANY of the following will be excluded from the study:;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:
* A myocardial infarction within the past 6 months.
* Uncontrolled angina within the past 3 months.
* Congestive heart failure within the past 3 months, defined as New York Heart Association (NYHA) Classes II or higher.
* 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 >140 mm Hg systolic and >90 mm Hg diastolic).
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 known 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 1 month after the last dose of study medication.
13. Weight loss >20% in the previous 6 months.
14. History of progressive multifocal leukoencephalopathy or other demyelinating disease
15. Subjects on immunosuppressive therapy, including transplant patients
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Efficacy Endpoint<br /><br><br /><br>* Overall survival (OS) will be the primary endpoint of this study, which will<br /><br>be measured from the date of randomization until death or last follow-up. </p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary Efficacy Endpoints<br /><br><br /><br>* Secondary efficacy variables will include change in lean body mass (LBM)<br /><br>measured by dual-energy X-ray absorptiometry (DEXA) scans, change in Quality of<br /><br>Life assessed through the cancer-specific EORTC QLQ-C30 questionnaire,<br /><br>stabilization of platelet counts, progression free survival (PFS), objective<br /><br>response rate (ORR) and disease control rate (DCR).</p><br>