Erlotinib and Combination Chemotherapy in Treating Patients With Metastatic Colorectal Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Combining erlotinib with combination chemotherapy may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of combining erlotinib with oxaliplatin, leucovorin, and fluorouracil in treating patients who have metastatic colorectal cancer.

Detailed Description
-----------------
OBJECTIVES: Determine the maximum tolerated dose of erlotinib when administered with oxaliplatin, leucovorin calcium, and fluorouracil in patients with metastatic colorectal cancer. Determine the pharmacokinetics of this regimen in these patients. Determine any antitumor activity of this regimen in these patients. Determine the time to progression in patients treated with this regimen. Determine the objective response rate and response duration in patients treated with this regimen. Determine the safety and tolerability of this regimen in these patients. OUTLINE: This is a dose-escalation study of erlotinib. Phase I: During the first week of the first course only, patients receive oral erlotinib daily alone. Patients then begin the regular schedule comprising oral erlotinib daily, oxaliplatin IV over 2 hours on day 1, and leucovorin calcium IV over 2 hours and fluorouracil IV over 22 hours on days 1 and 2. Treatment repeats every 2 weeks for at least 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Phase II: Patients receive erlotinib at the MTD plus oxaliplatin, leucovorin calcium, and fluorouracil as in phase I. Erlotinib may be administered alone if toxicity is caused by oxaliplatin, leucovorin calcium, and fluorouracil. Patients are followed for at least 6 months or until disease progression. PROJECTED ACCRUAL: A total of 4-18 patients will be accrued for phase I of this study within 1-4 months. A total of 50 patients will be accrued for phase II of this study within 10 months.

Official Title
-----------------
A Phase I/II Study Of OSI-774 In Combination With Oxaliplatin, And 5-Fluourouracil In Patients With Metastatic Colorectal Carcinoma

Conditions
-----------------
Colorectal Cancer

Intervention / Treatment
-----------------
* Drug: erlotinib hydrochloride
* Drug: fluorouracil
* Drug: leucovorin calcium
* Drug: oxaliplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed colon or rectal cancer Metastatic or unresectable disease Unidimensionally measurable disease required for phase II only At least 20 mm by x-ray, CT scan, MRI, or photography The following are not considered measurable: Pleural effusion or ascites Osteoblastic lesions Evidence of disease on bone scan alone Progressive irradiated lesions alone Bone marrow involvement Brain metastases Malignant hepatomegaly by physical exam alone Chemical markers (e.g., carcinoembryonic antigen) Recurrent disease after surgery or radiotherapy is considered measurable as long as the following criteria are met: At least 4 weeks since prior surgery or radiotherapy Measurable disease exists outside the radiation port or clear progression exists within the radiation port Tissue accessible for immunohistochemical evidence of epidermal growth factor receptor expression from a metastatic site (phase II only) No known brain metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 OR Karnofsky 60-100% Life expectancy More than 3 months Hematopoietic WBC at least 3,000/mm^3 Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic Bilirubin normal AST/ALT no greater than 2.5 times upper limit of normal Renal Creatinine normal OR Creatinine clearance at least 60 mL/min Cardiovascular No unstable angina pectoris No symptomatic congestive heart failure No cardiac arrhythmia No uncontrolled hypertension (systolic blood pressure greater than 150 mm Hg) Opthalmic No abnormalities of the cornea (e.g., severe dry eye syndrome or Sjogren's syndrome) No congenital abnormality (e.g., Fuch's dystrophy) No abnormal slit-lamp examination using vital dye (e.g., fluorescein or Bengal-Rose) No abnormal corneal sensitivity test (e.g., Schirmer test or similar tear-production test) Mild dry eye syndrome allowed if patient can use artificial tears and ophthalmologist concurs Gastrointestinal No gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation No active peptic ulcer disease Other Must be able and willing to undergo a mediport insertion Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other malignancy within the past 5 years except previously excised and inactive basal cell or squamous cell skin cancer No prior allergic reactions attributed to compounds of similar chemical or biological composition to erlotinib or other study drugs (e.g., epidermal growth factor inhibitors like cetuximab) No significant traumatic injury within the past 3 weeks No peripheral neuropathy grade 2 or greater No ongoing or active infection No other uncontrolled concurrent illness that would preclude study entry No psychiatric illness or social situation that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered Phase I: Prior chemotherapy allowed Phase II: No prior chemotherapy for metastatic disease Prior adjuvant therapy allowed if disease progresses during adjuvant therapy No prior oxaliplatin Endocrine therapy Not specified Radiotherapy See Disease Characteristics More than 4 weeks since prior radiotherapy and recovered Surgery See Disease Characteristics More than 3 weeks since prior major surgery and recovered No prior surgical procedures affecting absorption Other No other concurrent investigational agents No other concurrent anticancer agents or therapies (commercial or investigational) No concurrent combination antiretroviral therapy for HIV-positive patients

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: erlotinib hydrochloride|nan|
|Drug: fluorouracil|nan|
|Drug: leucovorin calcium|nan|
|Drug: oxaliplatin|nan|

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

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
recurrent colon cancer, stage IV colon cancer, recurrent rectal cancer, stage IV rectal cancer