Irinotecan and Cetuximab for Colorectal Cancer as Second Line Therapy

A Phase 2 Study of Irinotecan and Cetuximab on an Every 2 Week Schedule, as Second Line Therapy in Patients With Advanced Colorectal Cancer

Research Hypothesis: Subjects in the study population who are treated with cetuximab in combination with irinotecan will have higher response rates than subjects treated with irinotecan alone.

Primary Objective:

·The primary aim of this study is to assess the response rate of patients with previously treated colorectal cancer (CRC) Number of Subjects: 31

Study Population:

Subjects with metastatic, CRC who have failed a first-line chemotherapeutic regimen containing oxaliplatin and a fluoropyrimidine, and who have not previously received irinotecan or cetuximab for treatment of CRC.

Test Product, Dose and Mode of Administration, Duration of Treatment:

Cetuximab administered at an initial dose of 500 mg/m2 intravenously (IV) over 120 minutes, followed by 500 mg/m2 every 2 weeks IV over 60 minutes.

Reference Therapy, Dose and Mode of Administration, Duration of Treatment: Irinotecan administered at a dose of 150a or 180 mg/m2 IV over 60 minutes every two weeks.

Inclusion Criteria:

• Patients must consent to be in the study
• Patients must have advanced, surgically unresectable CRC, who have failed a first line metastatic regimen, within 12 months of starting protocol therapy.
• Patients must have measurable disease
• There must be histologic confirmation of adenocarcinoma of the colon or rectum.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Estimated life expectancy of at least 12 weeks.
• One prior therapy for metastatic disease is permitted.
• Recurrence within 12 months of adjuvant therapy with FOLFOX or a similar regimen (i.e FLOX, CapOX) is considered one regimen and allowed for study
• There must be evidence of adequate organ function
• Patients with a history of prior non-colorectal malignancies are eligible if they have been disease-free for ³ 5 years prior to study entry and are deemed by the physician to be at low risk for recurrence.
• Age > 18 yrs.

Exclusion Criteria:

• Any prior therapy with irinotecan or cetuximab or an EGFR targeting agent.
• Any systemic therapy administered for metastatic or locally recurrent colorectal cancer within 28 days of study treatment.
• Patients who are considered candidates for surgical resection of metastatic and/or locally advanced disease.
• Any histology other than adenocarcinoma of the colon or rectum.
• Serious concomitant medical conditions that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study.
• Evidence of central nervous system metastases
• Pulmonary fibrosis or interstitial pneumonitis
• General Medical Concerns
• History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications.
• Serious, uncontrolled, concurrent infection.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study; fine needle aspirations or core biopsies within 7 days prior to Day 0. Line placement (i.e Infus-a-port or PICC) is not considered major surgery.
• Evidence of bleeding diathesis or coagulopathy
• Prior severe infusion reaction to a monoclonal antibody.
• Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction.
• Patients with Gilbert's Syndrome
• Prior to study enrollment, women of childbearing potential (WOCBP) must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control.
• All WOCBP MUST have a negative pregnancy test within 7 days prior to first receiving investigational product. If the pregnancy test is positive, the patient must not receive investigational product and must not be enrolled in the study.
• In addition, all WOCBP should be instructed to contact the Investigator immediately if they suspect they might be pregnant (e.g., missed or late menstrual period) at any time during study participation.
• The Investigator must immediately notify BMS in the event of a confirmed pregnancy in a patient participating in the study.