Erlotinib in Treating Patients With Recurrent or Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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Biological therapies such as erlotinib may interfere with the growth of tumor cells and slow the growth of the tumor. Phase II trial to study the effectiveness of erlotinib in treating patients who have recurrent or metastatic colorectal cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the efficacy of erlotinib, in terms of response rate and duration of stable disease, in patients with recurrent or metastatic colorectal cancer. II. Determine the toxicity of this drug in these patients. III. Determine the time to progression and response duration in patients treated with this drug. IV. Determine the relationships between clinical, pharmacokinetic, and pharmacodynamic effects of this drug in these patients. V. Correlate baseline and post-treatment levels of epidermal growth factor receptor, its downstream signaling components, markers of angiogenesis, and apoptosis in tumor and skin biopsies with clinical outcome in patients treated with this drug. OUTLINE: This is a multicenter study. Patients receive oral erlotinib once daily. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients with a complete response (CR) receive 2 additional courses after CR is confirmed. Patients are followed every 8 weeks. PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 4-8 months.

Official Title
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A Phase II Study of OSI-774 in Metastatic Colorectal Cancer

Conditions
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Adenocarcinoma of the Colon, Adenocarcinoma of the Rectum, Recurrent Colon Cancer, Recurrent Rectal Cancer, Stage IV Colon Cancer, Stage IV Rectal Cancer

Intervention / Treatment
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* Drug: erlotinib hydrochloride
* Other: pharmacological study
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed adenocarcinoma of the colon or rectum that is not curable with conventional therapy Recurrent or metastatic disease At least 1 unidimensionally measurable lesion At least 20 mm by conventional techniques At least 10 mm by spiral CT scan Target lesion must not be in a previously irradiated field unless progression of this lesion has been documented No known brain metastases Performance status - ECOG 0-2 Performance status - Karnofsky 60-100% More than 3 months WBC at least 1,500/mm^3 Absolute granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Bilirubin no greater than 1.25 times upper limit of normal (ULN) AST or ALT no greater than 3 times ULN (5 times ULN if liver metastases present) Creatinine no greater than 1.25 times ULN Creatinine clearance at least 50 mL/min No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia No gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation No active peptic ulcer disease No unresolved complete or subacute bowel obstruction No severe enteropathy that would interfere with absorption of study drug No abnormalities of the cornea: Dry eye syndrome or Sjogren's syndrome Congenital abnormality (e.g., Fuch's dystrophy) Abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose) Abnormal corneal sensitivity test (Schirmer test or similar tear production test) No significant traumatic injury within the past 21 days No ongoing or active infection No psychiatric illness or social situation that would preclude study No other concurrent uncontrolled illness that would preclude study No other malignancy within the past 3 years except curatively treated nonmelanoma skin cancer or carcinoma in situ of the cervix Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No more than 1 prior chemotherapy regimen for metastatic disease with either fluorouracil (5-FU) and oxaliplatin or 5-FU and a topoisomerase inhibitor (e.g., irinotecan), OR 5-FU (or other single-agent fluoropyrimidine, such as capecitabine) followed by irinotecan for advanced disease Prior adjuvant chemotherapy allowed At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered See Disease Characteristics At least 4 weeks since prior radiotherapy and recovered At least 3 weeks since prior major surgery No prior surgical procedures affecting absorption No prior epidermal growth factor receptor-targeting therapy No other concurrent investigational therapies No other concurrent anticancer therapy No concurrent combination anti-retroviral therapy for HIV-positive patients No concurrent warfarin Low molecular weight heparin allowed

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (erlotinib hydrochloride)<br>Patients receive oral erlotinib once daily. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients with a CR receive 2 additional courses after CR is confirmed. | Drug: erlotinib hydrochloride<br>* Given orally<br>* Other names: OSI-774;Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response or disease stabilization |  | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Molecular changes with therapy | Will be examined using logistic regression or Fisher's exact tests as appropriate. | Up to 5 years |