Levocetirizine + Capecitabine + Bevacizumab for Patients With Refractory Colorectal Cancer

• ClinicalTrials.gov Identifier: NCT01722162
• Recruitment Status: Completed
• First Posted: November 6, 2012
• Results First Posted: February 13, 2017
• Last Update Posted: April 20, 2017
• Sponsor: Washington University School of Medicine
• Information provided by (Responsible Party): Washington University School of Medicine

Study Description

Brief Summary:

This randomized phase II trial studies how giving a drug called levocetirizine to patients with colorectal cancer affects their tumor response to capecitabine and bevacizumab. Capecitabine is a chemotherapy drug that blocks tumor growth by disrupting DNA and RNA synthesis and repair (cell division and survival). Bevacizumab is a monoclonal antibody that blocks the ability of tumors to grow and spread by inhibiting the growth of blood vessels that feed them. Patients with colorectal cancer can develop a resistance to the effects of bevacizumab. Levocetirizine may decrease tumor resistance to bevacizumab. Giving bevacizumab, capecitabine, and levocetirizine dihydrochloride together may be an effective treatment for refractory colorectal cancer.

Condition or disease	Intervention/treatment	Phase
Colorectal Neoplasms	Drug: Bevacizumab; Drug: Capecitabine; Drug: Levocetirizine	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 47 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Levocetirizine in Combination With Capecitabine + Bevacizumab to Overcome Resistance to Anti-angiogenic Therapy in Patients With Refractory Colorectal Cancer
• Study Start Date: April 2013
• Actual Primary Completion Date: October 2015
• Actual Study Completion Date: October 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm A: (start levocetirizine after bevacizumab/capecitabine); Bevacizumab IV 5 mg/kg on Days 1 each 2-week cycle. Capecitabine PO 850 mg/m2 twice a day on Days 1-7 of each 2 week cycle. Levocetirizine PO 5 mg daily before bed starting on Day 8 of Cycle 1. 5 mg daily before bed Days 1-4 of each cycle starting with cycle 2.	Drug: Bevacizumab; Other Name: Avastin®; Drug: Capecitabine; Other Name: Xeloda®; Drug: Levocetirizine; Other Name: Xyzal
Experimental: Arm B: (start levocetirizine before bevacizumab/capecitabine); Bevacizumab IV 5 mg/kg on Days 1 each 2-week cycle. Capecitabine PO 850 mg/m2 twice a day on Days 1-7 of each 2 week cycle. Levocetirizine PO 5 mg daily starting 7 days prior to initiation of bevacizumab and capecitabine therapy. 5 mg daily Days 1-14 starting with cycle 2.	Drug: Bevacizumab; Other Name: Avastin®; Drug: Capecitabine; Other Name: Xeloda®; Drug: Levocetirizine; Other Name: Xyzal

Outcome Measures

Primary Outcome Measures :

1. Progression Free Survival (Arm A) [ Time Frame: Until progressive disease (PD) (estimated to be 92 days) ]
   • Time from start of treatment to the time of progression or death, whichever occurs first
   • Progressive disease (target lesions): at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
   • Progressive disease (non-target lesions): appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.
2. Progression Free Survival (Arm B) [ Time Frame: Until progressive disease (PD) (up to 60 days) ]
   • Time from start of treatment to the time of progression or death, whichever occurs first
   • Progressive disease (target lesions): at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
   • Progressive disease (non-target lesions): appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.

Secondary Outcome Measures :

1. Incidence and Severity of Adverse Events as Measured by Number of Participants Who Experience Grade 3 and Higher Adverse Events [ Time Frame: Up to 6 months ]
   NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patient must have histologically or cytologically confirmed refractory colorectal cancer (CRC).
• Patient must have measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥10 mm with CT scan, as ≥20 mm by chest x-ray, or ≥10 mm with calipers by clinical exam.
• Patient must have documented progressive disease within 3 months of his/her most recent cycle of chemotherapy.
• Patient must be refractory to or intolerant of prior therapy with a fluoropyrimidine, oxaliplatin, irinotecan, and/or anti-angiogenic therapy. Patients with K-RAS wild type tumors must have received an epidermal growth factor receptor (EGFR) inhibitor such as cetuximab or panitumumab.
• Patient must be ≥ 18 years of age.
• Patient must have an ECOG performance status ≤ 2

• Patient must have normal bone marrow and organ function as defined below:

  • Absolute neutrophil count ≥ 1,500/mcl
  • Platelets ≥ 100,000/mcl
  • Total bilirubin ≤ 2.0 x IULN
  • AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
  • Patients must have adequate renal function prior to chemotherapy defined as serum creatinine ≤ 2.0 mg/dl OR Creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above 2.0
• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
• Patient must be able to understand and willing to sign an IRB approved written informed consent document.

Exclusion Criteria:

• Patient must not have a history of other malignancy ≤ 3 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
• Patient must not be receiving any other investigational agents.
• Patient must not have known active brain metastases. Patients with previously treated brain metastases are eligible. Patients with known brain active metastases must be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Patient must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to levocetirizine, capecitabine, bevacizumab, or other agents used in the study.
• Patient must not have known dihydropyrimidine dehydrogenase (DPD) deficiency or severe renal impairment (creatinine clearance below 30 mL/min by Cockcroft and Gault formula) as this would prelude use of capecitabine.
• Patient must not have known proteinuria ≥ 500mg/24 hours.
• Patient must not have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patient must not be pregnant and/or breastfeeding. Patient must have a negative urine pregnancy test within seven days of study entry.
• Patient must not be known to be HIV-positive on combination antiretroviral because of the potential for pharmacokinetic interactions with levocetirizine, capecitabine, and bevacizumab. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.

Contacts and Locations

Locations

United States, Missouri

Washington University School of Medicine

St. Louis, Missouri, United States, 63110

Sponsors and Collaborators

Washington University School of Medicine

Investigators

• Principal Investigator: Manik A Amin, M.D.; Washington University School of Medicine

More Information

Additional Information:

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine 

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT01722162
• Other Study ID Numbers: 201303043
• First Posted: November 6, 2012
• Results First Posted: February 13, 2017
• Last Update Posted: April 20, 2017
• Last Verified: March 2017

Additional relevant MeSH terms:

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Bevacizumab; Capecitabine; Levocetirizine; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Histamine H1 Antagonists, Non-Sedating; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Neurotransmitter Agents