Colorectal Cancer
Conditions
Keywords
recurrent colon cancer, stage IV colon cancer, recurrent rectal cancer, stage IV rectal cancer
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. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving cetuximab together with capecitabine may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving cetuximab together with capecitabine work in treating patients with metastatic colorectal cancer.
Detailed description
OBJECTIVES: Primary * Determine the response rate in patients with metastatic colorectal cancer treated with cetuximab and capecitabine that progressed on prior fluoropyrimidine-containing therapy comprising irinotecan with or without oxaliplatin. Secondary * To determine the progression-free survival and overall survival of patients treated with this regimen. * To determine the tolerance to therapy in these patients. * To assess biological correlates of response in available tissue biopsies and blood samples. OUTLINE: Patients receive cetuximab IV over 1-2 hours on days 1, 8, and 15 and oral capecitabine twice daily on days 1-14. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo tumor tissue and blood collection periodically for correlative studies. Samples are analyzed for expression of genes correlated with fluoropyrimidine responsiveness via quantitation RT-PCR; degree of expression of EGFR via immunohistochemistry; and expression pattern analysis via gene expression profiling and polymorphism. After completion of study treatment, patients are followed periodically.
Interventions
BIOLOGICALcetuximab
DRUGcapecitabine
GENETICgene expression analysis
GENETICmicroarray analysis
GENETICpolymorphism analysis
GENETICreverse transcriptase-polymerase chain reaction
OTHERimmunohistochemistry staining method
Sponsors
National Cancer Institute (NCI)
City of Hope Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Diagnosis of metastatic colorectal cancer * Measurable disease * Disease progression during prior fluoropyrimidine-containing therapy comprising irinotecan with or without oxaliplatin * Received standard first- and second-line irinotecan and oxaliplatin-based therapy * Patients who completed 1 prior treatment for metastatic disease but refused standard second-line therapy are eligible * Patients who's disease progressed within 6 months of previous therapy are eligible * EGFR negative patients allowed * No untreated or uncontrolled brain metastasis PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Absolute neutrophil count ≥ 1,500/μL * Platelet count ≥ 100,000/μL * ALT ≤ 5 times upper limit of normal (ULN) * Alkaline phosphatase ≤ 5 times ULN * Serum creatinine ≤ 1.5 mg/dL * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No other prior malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix * No serious intercurrent infections or medical problems * No active or uncontrolled infections * No significant history of uncontrolled cardiac disease, including any of the following: * Uncontrolled hypertension * Unstable angina * Myocardial infarction within the past 6 months * Uncontrolled congestive heart failure * Cardiomyopathy with decreased ejection fraction * No prior severe infusion reaction to a monoclonal antibody * No known dihydropyrimidine dehydrogenase deficiency or evidence of past hypersensitivity to fluoropyrimidine PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No more than 2 prior treatments for metastatic colorectal cancer * More than 2 weeks since prior therapy * Prior radiotherapy allowed if \< 30% of bone marrow involvement * No other concurrent investigational agents * No concurrent highly active antiretroviral therapy for HIV-positive patients * No prior therapy that specifically and directly targets the EGFR pathway
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | Assessment after every 2 cycles of treatment, up to 1 year. | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by spiral CT scan: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 Cetuximab 400mg/m2 IV on day 1 over 2 hours then 250 mg/m2 over 1 hour weekly + Xeloda(Capecitabine) 1000mg/m2 BID on days 1-14 repeated every 21 days. | 13 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Arm 1 |
|---|---|
| Age, Continuous | 61 years |
| Region of Enrollment United States | 13 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 13 / 13 |
| serious Total, serious adverse events | 4 / 13 |
Outcome results
Primary
Response Rate
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by spiral CT scan: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: Assessment after every 2 cycles of treatment, up to 1 year.
Population: The three patients not completing at least two courses of treatment were considered treatment failures and were included in efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Response Rate | 1 number of responding participants |