Combination of CPT-11 and LoHP vs Combination of 5-FU, Leucovorin and LoHP as 1st Line Treatment in Gastric Patients

Study Overview
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Brief Summary
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This phase II trial will compare the efficacy and toxicity of the combination of Irinotecan and Oxaliplatin versus 5-FU/LV and Oxaliplatin as first line treatment in patients with locally advanced or metastatic gastric cancer

Detailed Description
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There is no regimen considered standard in advanced gastric cancer. The reported response rates of 5-FU-based combination chemotherapy are higher than single agents (10-50%) but more toxic. The combination of 5-FU/LV and LOHP has demonstrated an ORR of 43%, median TTP of approximately 6,5 months and OS of 8,6 months in phase II trials, with an acceptable toxicity. Irinotecan (CPT-11) is effective as salvage treatment in metastatic gastric cancer and has a synergistic activity with LOHP in preclinical trials

Official Title
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A Randomized Phase II Study of Irinotecan and Oxaliplatin Versus the Combination of 5-FU/LV and Oxaliplatin, as First-Line Treatment in Patients With Locally Advanced or Metastatic Gastric Cancer

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: Irinotecan
* Drug: Oxaliplatin
* Drug: Fluorouracil
* Drug: Leucovorin
* Drug: Oxaliplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed locally advanced or metastatic gastric cancer. Measurable or evaluable disease. Measurable disease is defined as at least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or 1 bidimensionally measurable lesion ≥ 20 X 10 mm. Lesions that are smaller or uni- or bidimensionally unmeasurable are considered as evaluable disease. Previous adjuvant chemotherapy with Irinotecan, Oxaliplatin and/or 5-FU based regimen. Patients who relapse within the first 6 months after the completion of adjuvant treatment are not eligible for the study. Karnofsky performance status > 70%. Age ≥18 years. Adequate liver (Bilirubin ≤ 1.5 UNL, SGOT/SGPT ≤ 4 UNL, ALP ≤ 2.5 UNL), renal (Creatinine ≤ 1.5 UNL) and bone marrow (ANC ≥ 1,500/mm3, PLT ≥ 100,000/mm3) function. Patients must be able to understand the nature of this study and give written informed consent. Exclusion Criteria: Active infection History of serious cardiac disease (unstable angina, congestive heart failure, myocardial infarction within the previous 6 months, ventricular arrhythmias) Previous radiotherapy within the last 4 weeks or > 25% of bone marrow. Patients with CNS metastases Patients with chronic diarrhea (at least for 3 months) or partial bowel obstruction. Malnutrition or loss of > 10% of body weight during the last month. Peripheral neuropathy ≥ grade 2 Second primary malignancy, except for non-melanoma skin cancer and in situ cervical cancer. Psychiatric illness or social situation that would preclude study compliance. Pregnant or lactating women.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>IOX | Drug: Irinotecan<br>* Irinotecan 200 mg/m2 IV on Day 1 every 3 weeks for 6 cycles<br>* Other names: CPT-11;Drug: Oxaliplatin<br>* Oxaliplatin 80 mg/m2 IV on Day 2 every 3 weeks for 6 cycles<br>* Other names: LoHP;|
| Experimental: 2<br>FLOX | Drug: Fluorouracil<br>* Fluorouracil 400 mg/m2 infused over 10 min IV and Fluorouracil600 mg/m2 infused over 22 hours IV, Day 1 and 2 (De Grammont regimen)every 2 weeks for 12 cycles<br>* Other names: 5-FU;Drug: Leucovorin<br>* Leucovorin 200 mg/m2 infused over 1 hour IV on day 1 and day 2 (De Grammont regimen) every 2 weeks for 12 cycles<br>* Other names: LV;Drug: Oxaliplatin<br>* Oxaliplatin 85 mg/m2 as a 4 hour IV infusion, Day 1 every 4 weeks for 6 cycles<br>* Other names: LoHP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rates |  | Objective responses confirmed by CT or MRI (on 3rd and 6th cy) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression |  | 1 year | 
| Toxicity |  | Toxicity assessment on each chemotherapy cycle | 
| Overall survival |  | 1 year | 
| Quality of life |  | Assessment every two cycles | 
| Symptoms improvement |  | Assessment every two cycles | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic Gastric Cancer, Oxaliplatin, Irinotecan