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Phase II Study of Levocetirizine in Combination With Capecitabine + Bevacizumab to Overcome Resistance to Anti-angiogenic Therapy in Patients With Refractory Colorectal Cancer

Phase 2
18 Years
Open (Enrolling)
Colorectal Neoplasms

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Trial Information

Phase II Study of Levocetirizine in Combination With Capecitabine + Bevacizumab to Overcome Resistance to Anti-angiogenic Therapy in Patients With Refractory Colorectal Cancer

Even though anti-angiogenic drugs have had a significant impact on treatment outcomes in
patients with colorectal cancers, eventually all patients in the metastatic setting develop
disease progression, likely due to tumor resistance to chemotherapy and to anti-VEGF
therapy. One of the mechanisms of evasive resistance to an anti-VEGF regimen involves
upregulation of alternative pro-angiogenic signaling pathways. Blocking one of these
alternate pathways may affect a tumor's ability to continue to grow and metastasize. We
therefore propose to treat patients with refractory colorectal cancer with a combination
anti-VEGF treatment regimen and an IL-8 inhibitor to study the effects on patients' tumor
response and their systemic cytokine profile. We hypothesize that by altering cytokine
levels through inhibition of IL-8 may increase PFS in some patients by decreasing or
delaying resistance to antiangiogenic therapy.

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


- 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.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Median progression free survival

Outcome Time Frame:

14 days and 28 days after progression

Safety Issue:


Principal Investigator

Craig Lockhart, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Washington University School of Medicine


United States: Institutional Review Board

Study ID:




Start Date:

April 2013

Completion Date:

August 2014

Related Keywords:

  • Colorectal Neoplasms
  • Neoplasms
  • Colorectal Neoplasms



Washington University School of Medicine Saint Louis, Missouri  63110