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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2015 by XBiotech, Inc.
Sponsor:
Information provided by (Responsible Party):
XBiotech, Inc.
ClinicalTrials.gov Identifier:
NCT01767857
First received: January 8, 2013
Last updated: March 2, 2015
Last verified: March 2015
  Purpose

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 Intervention Phase
Metastatic Colorectal Cancer
Drug: Xilonix
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase III Double-blinded, Placebo Controlled Study of Xilonix™ for Improving Survival in Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by XBiotech, Inc.:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: baseline to 18 months ] [ Designated as safety issue: No ]
    The difference in median overall survival will be compared between the two arms.


Secondary Outcome Measures:
  • Change in Lean Body Mass [ Time Frame: baseline to 8 weeks ] [ Designated as safety issue: No ]
    Change in LBM as measured by DEXA scan will be compared between the two arms

  • Quality of life questionnaire [ Time Frame: baseline to 8 weeks ] [ Designated as safety issue: No ]
    EORTC-QLQ C30

  • Progression Free Survival [ Time Frame: baseline to 18 months ] [ Designated as safety issue: No ]
    The difference in median PFS will be compared between the two arms

  • Objective Response Rate [ Time Frame: baseline to 18 months ] [ Designated as safety issue: No ]
    The ORR will be compared between the two arms


Estimated Enrollment: 600
Study Start Date: March 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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.
Other Name: Placebo

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01767857

Contacts
Contact: Michael Stecher, M.D. 512-386-2900

  Show 29 Study Locations
Sponsors and Collaborators
XBiotech, Inc.
Investigators
Study Chair: George Fisher, M.D., Ph.D. Stanford University
  More Information

Publications:
Responsible Party: XBiotech, Inc.
ClinicalTrials.gov Identifier: NCT01767857     History of Changes
Other Study ID Numbers: 2012-PT023
Study First Received: January 8, 2013
Last Updated: March 2, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by XBiotech, Inc.:
Pivotal
Colorectal
Survival
Phase 3

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases

ClinicalTrials.gov processed this record on May 26, 2015