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A Phase 2 Study of Cetuximab in Combination With Celecoxib in Colorectal Cancer

Phase 2
18 Years
Not Enrolling
Colorectal Cancer

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Trial Information

A Phase 2 Study of Cetuximab in Combination With Celecoxib in Colorectal Cancer



- Determine the time to progression in patients with unresectable or metastatic
colorectal cancer treated with cetuximab and celecoxib.


- Determine the response rate, median survival, and 1-year survival rate of patients
treated with this regimen.

- Determine the toxicity profile of this regimen in these patients.

- Determine the feasibility of testing urinary PGE-M in patients treated with this

- Determine the feasibility of testing serum transforming growth factor-α and
amphiregulin in patients treated with this regimen.

- Determine the effects of this regimen on the EGFR pathway in tumor cells (i.e.,
phosphorylated EGFr, phosphorylated AKT, activated mitogen-activated protein kinase).

- Determine the effects of this regimen on the cyclooxygenase-2 pathway in tumor cells by
measuring PGE-2 levels.

OUTLINE: Patients receive cetuximab IV over 1-2 hours once weekly and oral celecoxib twice
daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity.

Serum and urine samples are collected at baseline, after week 1, and every other course
thereafter for evaluation of PGE-2 by mass spectrometry, cyclooxygenase-2 activity, and
phospho-EGFR levels by western blot analysis and immunohistochemistry. Samples are also
analyzed for TGF-α and amphiregulin proteomics.

PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study.

Inclusion Criteria:

- Patients must have histologically confirmed colorectal cancer that is metastatic or
unresectable and for which standard curative or palliative measures do not exist or
are no longer effective.

- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as >
or equal to 20 mm with conventional techniques or as > or equal 10 mm with spiral CT

- Patients must have progressed after at least 1 chemotherapy regimen for advanced
disease. No prior therapy which specifically and directly targets the EGFR pathway.

- Age 18 years or older

- ECOG performance status ≤ 2.

- Life expectancy of greater than 3 months.

- Normal organ and marrow functions as defined below:

- absolute neutrophil count ≤ 1,500/μl

- platelets ≤ 100,000/μl

- total bilirubin within normal institutional limits

- AST(SGOT)/ALT(SGPT) > or equal to 2.5 times institutional upper limit of normal
or > or equal to 5.0 times normal if liver metastases are present

- creatinine within normal institutional limits OR

- creatinine clearance > or equal to 60 mL/min/1.73 m2 for patients
creatinine levels above institutional normal

- The effects of cetuximab and/or celecoxib on the developing human fetus at the
recommended therapeutic doses are unknown. For this reason, women of child-bearing
potential and men must agree to use adequate contraception (hormonal or barrier
method of birth control) 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 should inform her treating physician immediately.

- Ability to understand and the willingness to provide written informed consent.

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier.

- Patients may not be receiving any other investigational agents.

- Patients with known brain metastases should 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

- Prior severe infusion reaction to a monoclonal antibody

- Serum calcium >12.0 mg/dl.

- Patients must be off all other selective or non-selective COX-2 inhibitors for at
least 2 weeks prior to study entry (with the exception of 81 mg of daily aspirin).

- No major surgery within 4 weeks. No minor surgery (laparoscopy, thoracoscopy, port
placement) within 1 week.

- Patients must be > 4 weeks from prior pelvic radiation and recovered from side

- Patients must be > 1 week from prior palliative radiation and have recovered from all
side effects.

- Prior treatment with EGFR targeting therapies.

- Significant traumatic injury occurring within 28 days prior to treatment.

- Gastrointestinal tract disease resulting in an inability to take oral medication or a
requirement for IV alimentation, prior surgical procedures affecting absorption, or
active peptic ulcer disease.

- 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.

- Pregnant women are excluded from this study because cetuximab is an epidermal growth
factor inhibitor with the potential for teratogenic or abortifacient effects based on
the data suggesting that EGFR expression is important for normal organ development.
Because there is an unknown but potential risk for adverse events in nursing infants
secondary to treatment of the mother with cetuximab, breastfeeding should be
discontinued if the mother is treated with cetuximab.

- Patients with known HIV disease.

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free Survival (PFS)

Outcome Description:

Number of days from study enrollment to evidence of progressive disease radiographically, with progression defined under RECIST criteria as at least 20% increase in sum of longest diameter of target lesions

Outcome Time Frame:

On study date to off study date in this study with median 9.76 months

Safety Issue:


Principal Investigator

Jordan D. Berlin, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Vanderbilt-Ingram Cancer Center


United States: Food and Drug Administration

Study ID:

VICC GI 0410



Start Date:

May 2005

Completion Date:

November 2008

Related Keywords:

  • Colorectal Cancer
  • recurrent colon cancer
  • stage IV colon cancer
  • recurrent rectal cancer
  • stage IV rectal cancer
  • Colorectal Neoplasms



Vanderbilt-Ingram Cancer Center Nashville, Tennessee  37232-6838