Gefitinib and Combination Chemotherapy in Treating Patients With Advanced or Recurrent Colorectal Cancer

Study Overview
=================
Brief Summary
-----------------
Phase II trial to study the effectiveness of combining gefitinib with fluorouracil, leucovorin, and irinotecan in treating patients who have advanced or recurrent colorectal cancer. Biological therapies such as gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining gefitinib with fluorouracil, leucovorin, and irinotecan may kill more tumor cells

Detailed Description
-----------------
OBJECTIVES: I. Determine the safety of gefitinib, fluorouracil, leucovorin calcium, and irinotecan in patients with advanced or recurrent colorectal cancer. II. Determine the major side effects of this regimen in these patients. III. Determine the response rate, progression-free survival, and overall survival of patients treated with this regimen. IV. Correlate response and other measures of outcome with epidermal growth factor receptor expression and the expression of genes that impact upon pathways of fluoropyrimidine cytotoxicity in patients treated with this regimen. OUTLINE: This is a non-randomized, open-label, multi-center study. Patients receive oral gefitinib daily beginning on day 1, irinotecan IV over 90 minutes on days 1 and 15, and leucovorin calcium IV over 2 hours and fluorouracil IV over 3-5 seconds followed by a 22-hour infusion on days 1, 2, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Official Title
-----------------
A Phase II Trial Of IRESSA (NSC 715055, IND 61187) In Combination With 5-FU/LV/ CPT-11 In Patients With Advanced Or Recurrent Colorectal Cancer

Conditions
-----------------
Adenocarcinoma of the Colon, Adenocarcinoma of the Rectum, Mucinous Adenocarcinoma of the Colon, Mucinous Adenocarcinoma of the Rectum, Recurrent Colon Cancer, Recurrent Rectal Cancer, Signet Ring Adenocarcinoma of the Colon, Signet Ring Adenocarcinoma of the Rectum, Stage IV Colon Cancer, Stage IV Rectal Cancer

Intervention / Treatment
-----------------
* Drug: irinotecan hydrochloride
* Drug: gefitinib
* Drug: leucovorin calcium
* Drug: fluorouracil


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed advanced (stage IV) or recurrent adenocarcinoma of the colon or rectum Must have available tissue for immunohistochemical analysis At least one unidimensionally measurable lesion At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan Tumor marker (carcinoembryonic antigen) elevation alone is insufficient for study entry No known brain metastases Performance status - ECOG 0-2 Granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Bilirubin no greater than 1.5 times upper limit of normal (ULN) AST less than 2 times ULN (5 times ULN if liver involvement of tumor) Creatinine no greater than 1.5 times ULN No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Not pregnant or nursing Fertile patients must use effective contraception HIV negative No other severe or uncontrolled concurrent illness that would adversely impact the safety or efficacy of study therapy No ongoing or active infection No other prior malignancy unless curatively treated and no evidence of recurrence No history of allergic reactions attributed to compounds of similar chemical or biologic composition to gefitinib No psychiatric illness or social situation that would preclude study compliance No prior chemotherapy for advanced disease More than 4 weeks since other prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered More than 4 weeks since prior radiotherapy and recovered At least 6 months since prior adjuvant therapy No prior epidermal growth factor receptor inhibitor No other concurrent investigational agents No other concurrent anticancer therapy No concurrent phenytoin, carbamazepine, barbiturates, rifampin, rifapentine, oxacarbazepine, modafinil, griseofulvin, or Hypericum perforatum

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (irinotecan, gefitinib, leucovorin, fluorouracil)<br>Patients receive oral gefitinib daily beginning on day 1, irinotecan IV over 90 minutes on days 1 and 15, and leucovorin calcium IV over 2 hours and fluorouracil IV over 3-5 seconds followed by a 22-hour infusion on days 1, 2, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: irinotecan hydrochloride<br>* Given IV<br>* Other names: U-101440E;Drug: gefitinib<br>* Given orally<br>* Other names: ZD 1839;Drug: leucovorin calcium<br>* Given IV<br>* Other names: LV;Drug: fluorouracil<br>* Given IV<br>* Other names: 5-FU;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Grade 3 or 4 toxicity, graded using the NCI CTC version 2.0 |  | Up to 2 years | 
| Response rate | 95% confidence interval will be determined. | Up to 2 years |