Intermittent Versus Continuous Tarceva Study

Recruitment & Eligibility

Inclusion Criteria

Age ≥ 18 years.
ECOG performance status of 0-2.
Histological proof of adenocarcinoma of colon or rectum with evidence of metastatic disease.
At least one unidimensionally measurable lesion with a diameter >20 mm using conventional CT or MRI scans, or > 10 mm with spiral CT
No prior drug treatment or chemotherapy for metastatic disease.
No prior HER2 or EGFR inhibitors. No prior Oxaliplatin in any clinical setting.
Absolute granulocyte count > 1.5 x 109/L, platelet count > 100 x 109/L, hemoglobin level > 9.0 g/L, INR < 1.5.
Adequate renal & hepatic functions: serum creatinine < 1.5 x upper limit of normal (ULN) or calculated creatinine clearance > 50ml/min, serum bilirubin < 1.5 x ULN, ALT < 2.5 x ULN or < 5 x ULN in case of liver metastases, albumin level > 30g/dL).
Prior adjuvant or neoadjuvant chemotherapy for non-metastatic CRC is allowed if > 3 months has elapsed since the last dose of chemotherapy.
Prior open surgery is allowed if > 28 days* has elapsed since the date of surgery, wound healing is satisfactory and recovery from any complications from the surgery is adequate. (*For laparoscopic surgery, > 14 days from the date of surgery).
No serious medical conditions such as myocardial infarction within 6 months prior to entry, or any other medical conditions that might be aggravated by treatment

Exclusion Criteria

Prior history of any malignancies, except basal cell cancer of skin, cervical CIN.
Treatment with radiotherapy < 30 days.
Pregnant or lactating females
Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study.
Patients who have not recovered from surgery or other medical illness such as infection.
Evidence of central nervous system disease. Patients with a history of uncontrolled seizures, central nervous disorders or psychiatric disability judged by the investigator to be clinically significant precluding informed consent or interfering with compliance for oral drug intake should be excluded from the study
Patients lacking physical integrity of upper gastrointestinal tract or malabsorption syndrome or unable to swallow tablets.
Prior unanticipated severe reaction to fluoropyrimidine therapy (with or without documented DPD deficiency).
Interstitial pneumonia or extensive symptomatic fibrosis of the lungs.
Requirement for concurrent use of the antiviral agent sorivudine (antiviral) or chemically related analogues, such as brivudine.
Known peripheral neuropathy ≥ NCI CTC grade 1.
Current or recent (within 10 days prior to study treatment start) use of full-dose oral anticoagulant (e.g. warfarin) or thrombolytic agent.

Study & Design

Arm && Interventions

Group	Intervention	Description
Arm A	Chemotherapy	Continuous erlotinib administration (21-day cycle). Erlotinib dose given at 100mg daily
Arm B	Chemotherapy	Intermittent erlotinib administration (21-day cycle). Erlotinib dose given at 150mg.

Primary Outcome Measures

Name	Time	Method
To evaluate two different schedules of erlotinib in combination with a modified XELOX regimen in terms of response rate	3 years

Secondary Outcome Measures

Name	Time	Method
To evaluate two different schedules of erlotinib and modified XELOX regimen in terms of toxicity, their duration of response and effect on time to progression, progression-free survival and overall survival.	3 years
To determine the effect of intermittent versus continuous erlotinib administration on pharmacodynamic endpoints using tumor biopsies	3 years

Recruitment & Eligibility