Clinical trial NCT00466505
Conditions: Colorectal Cancer
Keywords: recurrent colon cancer stage IV colon cancer recurrent rectal cancer stage IV rectal cancer
Sponsor: Vanderbilt-Ingram Cancer Center
Start date: 2005-05-01; Completion date: 2008-11-01
Enrollment: 17 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief 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.

Detailed description:
OBJECTIVES:

Primary

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

Secondary

* 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 regimen.
* 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.

Arms: arm 1: None
Interventions: intervention 1: cetuximab intervention 2: celecoxib intervention 3: proteomic profiling intervention 4: immunohistochemistry staining method intervention 5: laboratory biomarker analysis intervention 6: mass spectrometry
Intervention descriptions: intervention 1: 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. intervention 2: 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. intervention 3: 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. intervention 4: phospho-EGFR levels using western blots of tissue extracts and immunohistochemistry on frozen and (if no other option available, paraffinembedded tissue sections). intervention 5: Serum samples obtained as above will be analyzed by proteomic analysis in order to determine biomarkers of treatment response and toxicity prediction. intervention 6: 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.

Protocol documents: