Phase II Study of Levocetirizine in Combination With Capecitabine + Bevacizumab to Overcome Resistance to Anti-angiogenic Therapy in Patients With Refractory Colorectal Cancer
- Patient must have histologically or cytologically confirmed refractory colorectal
- 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
- Patient must be able to understand and willing to sign an IRB approved written
informed consent document.
- 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.