Cetuximab & Celecoxib for Metastatic Colorectal Cancer or Colorectal Cancer That Cannot Be Removed by Surgery
|ClinicalTrials.gov Identifier: NCT00466505|
Recruitment Status : Completed
First Posted : April 27, 2007
Results First Posted : November 16, 2011
Last Update Posted : December 19, 2012
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.
|Condition or disease||Intervention/treatment||Phase|
|Colorectal Cancer||Biological: cetuximab Drug: celecoxib Genetic: proteomic profiling Other: immunohistochemistry staining method Other: laboratory biomarker analysis Other: mass spectrometry||Phase 2|
- 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 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||17 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Study of Cetuximab in Combination With Celecoxib in Colorectal Cancer|
|Study Start Date :||May 2005|
|Actual Primary Completion Date :||July 2008|
|Actual Study Completion Date :||November 2008|
|Experimental: Therapeutic Intervention||
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.
Other Name: Erbitux, IMC-C225Drug: celecoxib
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.
Other Name: celebrexGenetic: proteomic profiling
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.Other: immunohistochemistry staining method
phospho-EGFR levels using western blots of tissue extracts and immunohistochemistry on frozen and (if no other option available, paraffinembedded tissue sections).Other: laboratory biomarker analysis
Serum samples obtained as above will be analyzed by proteomic analysis in order to determine biomarkers of treatment response and toxicity prediction.Other: mass spectrometry
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.
- Progression-free Survival (PFS) [ Time Frame: On study date to off study date in this study with median 9.76 months ]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
- Patient Response to Treatment [ Time Frame: On study date to off study date in this study with median 9.76 months ]Number of patients in each response category according to RECIST criteria: Progressive disease (PD): >=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started. Complete response (CR): disappearance of all target lesions. Partial response (PR): >=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD. Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD.
- Overall Survival [ Time Frame: On study date to off study date in this study with median 9.76 months ]Median survival time in months, from on-study date to date of death
- One Year Survival Rate [ Time Frame: 1 year from on-study date ]Percent of patients who remain alive one year from on-study date
- Number of Patients With Each Worst-grade Toxicity Response [ Time Frame: On study date to off study date in this study with median 9.76 months ]Number of patients with worst-grade toxicity response of each grade (grade 1 to 5) following NCI Common Toxicity Criteria, with grade 1=mild adverse event; 2=moderate adverse event; 3=severe and undesirable adverse event; 4=life-threatening or disabling adverse event; 5=death.
- Urinary PGE-M : Treatment Cycle 1 [ Time Frame: on-study week 5 ]Measurement in ng/mL of a stable metabolite of prostaglandin E2 (PGE-M) in urine during treatment cycle 1
- Serum TGF-alpha: Treatment Cycle 1 [ Time Frame: on-study week 5 ]Measurement in ng/mL of tumor growth factor-alpha (TGF-alpha) in serum samples during treatment cycle 1
- Urinary PGE-M : Treatment Cycle 2 [ Time Frame: on-study week 9 ]Measurement in ng/mL of a stable metabolite of prostaglandin E2 (PGE-M) in urine during treatment cycle 2
- Serum TGF-alpha: Treatment Cycle 2 [ Time Frame: on-study week 9 ]Measurement in ng/mL of tumor growth factor-alpha (TGF-alpha) in serum samples during treatment cycle 2
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00466505
|United States, Tennessee|
|Vanderbilt-Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232|
|Principal Investigator:||Jordan D. Berlin, MD||Vanderbilt-Ingram Cancer Center|