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

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

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.

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer
• Intervention / Treatment: Genetic: gene expression analysis; Genetic: polymorphism analysis; Genetic: reverse transcriptase-polymerase chain reaction; Drug: capecitabine; Other: immunohistochemistry staining method; Genetic: microarray analysis; Biological: cetuximab

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.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010-3000
      • City of Hope Comprehensive Cancer Center
    • Pasadena, California, United States, 91105
      • City of Hope Medical Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Genetic: gene expression analysis; Genetic: polymorphism analysis; Genetic: reverse transcriptase-polymerase chain reaction; Drug: capecitabine; Other: immunohistochemistry staining method; Genetic: microarray analysis; Biological: cetuximab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Vincent Chung, MD, City of Hope Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: August 1, 2005
• Primary Completion (Actual): February 1, 2009
• Study Completion: December 7, 2022

Study Registration Dates

• First Submitted: October 1, 2007
• First Submitted That Met QC Criteria: October 1, 2007
• First Posted (Estimate): October 2, 2007

Study Record Updates

• Last Update Posted (Estimate): August 28, 2014
• Last Update Submitted That Met QC Criteria: August 19, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: stage IV rectal cancer; stage IV colon cancer; recurrent colon cancer; recurrent rectal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Capecitabine; Cetuximab
• Other Study ID Numbers: 05033; P30CA033572 (U.S. NIH Grant/Contract); CHNMC-05033; CDR0000567432 (Registry Identifier: NCI PDQ)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No