Intermittent Versus Continuous Tarceva Study

Study Overview
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Brief Summary
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This is a randomized phase II study comprising of two treatment arms in patients who are previously untreated for metastatic or recurrent colorectal cancer.

Detailed Description
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To evaluate two different schedules of erlotinib in combination with a modified XELOX regimen in terms of response rate

Official Title
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Intermittent Versus Continuous Erlotinib With Concomitant Modified 'Xelox' (q3W) in First-line Treatment of Metastatic Colorectal Cancer

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: Chemotherapy


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A<br>Continuous erlotinib administration (21-day cycle). Erlotinib dose given at 100mg daily | Drug: Chemotherapy<br>* Erlotinib, Oxaliplatin, Capecitabine<br>|
| Active Comparator: Arm B<br>Intermittent erlotinib administration (21-day cycle). Erlotinib dose given at 150mg. | Drug: Chemotherapy<br>* Erlotinib, Oxaliplatin, Capecitabine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate two different schedules of erlotinib in combination with a modified XELOX regimen in terms of response rate |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Second line treatment for metastatic colorectal cancer