Cetuximab and Capecitabine in Treating Patients With Metastatic Colorectal Cancer That Failed Irinotecan Treatment

Colorectal Cancer Clinical Trial

Official title:

CA225103: A Phase II Study of a Combination of Cetuximab and Capecitabine in Patients With Metastatic Colorectal Cancer After Progression on Previous Fluoropyrimidine Containing Therapy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00538291
• Other study ID #: 05033
• Secondary ID: P30CA033572CHNMC
• Status: Terminated
• Phase: Phase 2
• First received: October 1, 2007
• Last updated: August 19, 2014
• Start date: August 2005

Study information

• Verified date: August 2014
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 13
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Biological:
• cetuximab

Drug:
• capecitabine

Genetic:
• gene expression analysis

• microarray analysis

• polymorphism analysis

• reverse transcriptase-polymerase chain reaction

Other:
• immunohistochemistry staining method

Locations

Country	Name	City	State
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	City of Hope Medical Group	Pasadena	California

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Assessment after every 2 cycles of treatment, up to 1 year.	No