Levocetirizine + Capecitabine + Bevacizumab for Patients With Refractory Colorectal Cancer
Condition: Colorectal Neoplasms
MeSH terms: Colorectal Neoplasms
Intervention: Bevacizumab; Capecitabine; Levocetirizine
Intervention MeSH terms: Bevacizumab; Capecitabine; Levocetirizine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 47.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility 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.