Phase II Study of Oxaliplatin, Irinotecan, and Capecitabine in Advanced Gastric/Gastroesophageal Junction Carcinoma

Study Overview
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Brief Summary
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Drugs used in chemotherapy, such as oxaliplatin, irinotecan, and capecitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving more than one chemotherapy drug may kill more tumor cells. This phase II trial is studying how well giving oxaliplatin together with irinotecan and capecitabine works in treating patients with metastatic or inoperable locally advanced gastric cancer or gastroesophageal junction adenocarcinoma (cancer).

Detailed Description
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PRIMARY OBJECTIVES: I. To assess the total response rate of the oxaliplatin, irinotecan and capecitabine drug combination in advanced gastric/esophageal junction carcinoma. II. To assess the duration of total responses of the oxaliplatin, irinotecan and capecitabine drug combination in advanced gastric/esophageal junction carcinoma. OUTLINE: This is a multicenter study. Patients receive oxaliplatin IV over 2 hours and irinotecan IV over 30 minutes on days 1, 8, 15, and 22 and oral capecitabine twice daily on days 1-5, 8-12, 15-19, and 22-26. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity. Patients are followed annually. PROJECTED ACCRUAL: A total of 40-80 patients will be accrued for this study within 18 months.

Official Title
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Phase II Study of Oxaliplatin, Irinotecan, and Capecitabine in Advanced Gastric/Gastroesophageal Junction Carcinoma

Conditions
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Recurrent Gastric Cancer, Adenocarcinoma of the Gastroesophageal Junction, Diffuse Adenocarcinoma of the Stomach, Intestinal Adenocarcinoma of the Stomach, Mixed Adenocarcinoma of the Stomach, Stage IIIA Gastric Cancer, Stage IIIB Gastric Cancer, Stage IIIC Gastric Cancer, Stage IV Gastric Cancer

Intervention / Treatment
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* Drug: oxaliplatin
* Drug: irinotecan hydrochloride
* Drug: capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically or cytologically confirmed gastric adenocarcinoma or adenocarcinoma of the gastroesophageal junction. Patients must have metastatic or inoperable locally advanced disease; GE Junction tumor location should be documented in the patient's medical record chart using the Siewert classification below: Type I: Adenocarcinoma of the distal esophagus which usually arises from an area with specialized intestinal metaplasia of the esophagus and which may infiltrate the GE junction from above Type II: True carcinoma of the cardia arising from the cardiac epithelium or short segments with intestinal metaplasia at the GE junction Type III: Subcardial gastric carcinoma which infiltrates the GE junction and distal esophagus from below Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan No prior chemotherapy for metastatic or recurrent disease is allowed; one course of neoadjuvant chemotherapy and/or adjuvant chemotherapy with or without radiation therapy as primary treatment is acceptable; at least 4 weeks must have elapsed since prior radiation therapy; patients must have been off previous anti-cancer therapy for at least 4 weeks Life expectancy of >= 12 weeks ECOG performance status 0-2 Hemoglobin >= 9.5 g/dL Absolute neutrophil count >= 1,500/uL Platelets >= 100,000/uL Total bilirubin =< 1.5 mg/dL Creatinine =< 1.5 mg/dL OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal The effects of oxaliplatin, irinotecan, and capecitabine on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because these drugs are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier Patients may not be receiving any other investigational agents Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; patients should have no greater than grade 2 neuropathy History of allergic reactions attributed to compounds of similar chemical or biologic composition to oxaliplatin, irinotecan and capecitabine Patients with NYHA classification III or IV heart disease are ineligible Patients must not have a known hypersensitivity to 5-fluorouracil Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women are excluded from this study because the study drugs have the potential to cause teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the study drugs, breastfeeding should be discontinued if the mother is treated with oxaliplatin, irinotecan or capecitabine Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy; therefore, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with the study drugs; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated Patients who are unable to take oral medications are not eligible

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 (oxaliplatin, irinotecan, capecitabine)<br>Patients receive oxaliplatin IV over 2 hours and irinotecan IV over 30 minutes on days 1, 8, 15, and 22 and oral capecitabine twice daily on days 1-5, 8-12, 15-19, and 22-26. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity. | Drug: oxaliplatin<br>* Given IV<br>* Other names: L-OHP;Drug: irinotecan hydrochloride<br>* Given IV<br>* Other names: U-101440E;Drug: capecitabine<br>* Given orally<br>* Other names: Xeloda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rates (RR) in Metastatic Gastric/GE Junction Tumors | Response is defined as the number of patients with a CR (Complete Response) or PR (Partial Response) per Response Evaluation Criteria in Solid Tumor (RECIST criteria). Possible evaluations include: CR: Disappearance of all target lesions. PR: At least a 30% decrease in the size of target lesions. Progressive Disease (PD): At least a 20% increase in the size of the target lesions or appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage or increase of target lesions. | at 12 weeks (after 2 cycles of treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response (CR) and Partial Response (PR) Duration | The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). | at 40 months from study activation | 
| Overall Survival | Length of time patients survived after treatment | at 40 months from study activation |