Cetuximab & Celecoxib for Metastatic Colorectal Cancer or Colorectal Cancer That Cannot Be Removed by Surgery
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: cetuximab; celecoxib; proteomic profiling; immunohistochemistry staining method; laboratory biomarker analysis; mass spectrometry
Intervention description: 400 mg/m2 iv week 1, then 250 mg/m2 weekly thereafter, starting on day 1 and continuing until progressive disease, excessive toxicity or removal from study for other reasons listed in the protocol.; 200 mg po BID starting on day 1 and continuing until progressive disease, excessive toxicity or removal from study for other reasons listed in the protocol.; Serum samples obtained as above will be analyzed by proteomic analysis in order to determine biomarkers of treatment response and toxicity prediction. We will use LC-MS-MS or MALDITOF mass spectrometry.; phospho-EGFR levels using western blots of tissue extracts and immunohistochemistry on frozen and (if no other option available, paraffinembedded tissue sections).; Serum samples obtained as above will be analyzed by proteomic analysis in order to determine biomarkers of treatment response and toxicity prediction.; We will use LC-MS-MS or MALDITOF mass spectrometry. Before any tissues are received, the drug of interest is evaluated via MALDI mass spectrometry on a MDS/Sciex QStar QqTOF mass spectrometer.
Intervention MeSH terms: Celecoxib; Cetuximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: recurrent colon cancer; stage IV colon cancer; recurrent rectal cancer; stage IV rectal cancer

Summary:

      RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different
      ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and
      help kill them or carry tumor-killing substances to them. Cetuximab may also stop the growth
      of colorectal cancer by blocking blood flow to the tumor. Celecoxib may stop the growth of
      tumor cells by blocking some of the enzymes needed for cell growth. Giving cetuximab together
      with celecoxib may kill more tumor cells.

      PURPOSE: This phase II trial is studying how well giving cetuximab together with celecoxib
      works in treating patients with metastatic colorectal cancer or colorectal cancer that cannot
      be removed by surgery.
    

Eligibility criteria:

        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
             scan.

          -  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 events.

          -  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
             effects.

          -  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.