Phase II Trial of Lapatinib & Capecitabine for Patients With Refractory Advanced Colorectal Adenocarcinoma

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to find out how effective this combination is as a second line treatment for colorectal cancer that has spread from one part of the body to another (metastasized) or has not metastasized but is considered inoperable (unable to be removed by surgery). The side effects and survival experienced by subjects receiving these drugs will also be evaluated. This is a phase II research study.

Detailed Description
-----------------
To evaluate the response rate of lapatinib and capecitabine combination in patients with metastatic colon or rectal cancer. To evaluate the toxicity and tolerability of lapatinib and capecitabine in this population. To determine overall survival and disease free survival of lapatinib and capecitabine.

Official Title
-----------------
A Phase II Trial of Lapatinib and Capectiabine for Patients With Refractory Advanced Colorectal Adenocarcinoma (LAP109859)

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

Intervention / Treatment
-----------------
* Drug: lapatinib
* Drug: Capecitabine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age > 18 years Pathologically confirmed, locally advanced or metastatic adenocarcinoma of the colon or rectum Patients must have had progression of disease on prior therapy with an oxaliplatin-containing or irinotecan containing regimen Proper radiographic documentation of measurable disease using RECIST criteria ECOG performance status (PS) of 0 or 1 Laboratory parameters: Hgb: ≥ 9.0 g/dl ANC ≥ 1500/ul Platelet ≥ 100,000/ul Creatinine ≤ 2x ULN OR Creatinine clearance ≥ 30 mg/ml Bilirubin ≤ 2x ULN AST ≤ 2x ULN or 5X ULN if liver metastases are present Patient has signed informed consent Toxicities from prior therapy (except alopecia and neuropathy) must have resolved to grade 1 or better prior to enrollment Exclusion Criteria: Administration of more than one prior systemic chemotherapy for metastatic disease Pregnant or breast-feeding women: female patients must agree to use effective contraception, must be surgically sterile, or must be postmenopausal. Male patients must agree to use effective contraception or be surgically sterile. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate. All at-risk female patients must have a negative serum pregnancy test within 7 days prior to randomization. Active inflammatory bowel disease, significant bowel obstruction, or chronic diarrhea (grade 2). Known human immunodeficiency virus (HIV) positivity or acquired-immunodeficiency-syndrome (AIDS)-related illness. No previous or concurrent malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, or other cancer for which the patient has been disease-free for 3 years. Known CNS metastases Prior therapy which specifically and directly targets the EGFR pathway Significant history of uncontrolled cardiovascular disease, defined as: History of uncontrolled or symptomatic angina History of arrhythmias requiring medications, or clinically significant, with the exception of asymptomatic atrial fibrillation requiring anticoagulation Myocardial infarction < 6 months prior to study entry Cerebrovascular accident <6 months prior to study entry Uncontrolled or symptomatic congestive heart failure Ejection fraction below the institutional normal limit Any other cardiac condition, which in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient

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: 1<br> | Drug: lapatinib<br>* 1250mg by mouth daily one hour before or after breakfast on a continuous basis.<br>* Other names: Tykerb;Drug: Capecitabine<br>* 2000mg/m2 of body surface area (BSA), by mouth, divided into twice daily dosing. Capecitabine will be given for days 1 through 14 of a 21 day cycle.<br>* Other names: Xeloda;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate of Lapatinib/Capecitabine. |  | duration of study; on average 1 year |