Phase I/II Study of Paclitaxel Plus CPT-11 in Pts. With 2nd Line Chemotherapy of Inoperable or Recurrent GC.

Study Overview
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Brief Summary
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A phase I/II study is conducted to determine the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), and efficacy of a combination chemotherapy using CPT-11 and Paclitaxel in pre-treated patients with metastatic gastric cancer. The usefulness of the this regimen is evaluated by response rate, median survival time, and progression free survival.

Detailed Description
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Patients with pre-treated measurable metastatic gastric cancer were included in this trial. Patients received this combination chemotherapy repeated every 28 days until progression disease. Starting dose (dose level 1) were CPT-11 80 mg/m2 on day 1 and 15, Paclitaxel 60 mg/m2 on day 1 and 15. DLT was defined as follows (according to NCI-CTC version 2.0); Grade 4 neutropenia, thrombocytopenia(≥25000), Grade 3 neutropenia accompanied fever (>38℃) , and Grade 3 non-hematological toxicity (except for nausea, vomit, appetite loss , general fatigue, alopecia). Maximal Tolerated Dose (MTD) is determined when the incidence of critical toxicity exceeds 50% at a certain dose level. Response rate will be calculated according to RECIST criteria.

Official Title
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Phase I/II Study of Biweekly Administration Regimen of Paclitaxel Combined With CPT-11 in Patients With Second Line Chemotherapy of Inoperable or Recurrent Gastric Cancer(GC).

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: Taxol
* Drug: Campt, Topotesin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed metastatic or recurrent gastric cancer with prior treatment for advanced disease. Patients who have received 1cycle cancer therapy (radiotherapy, chemotherapy or chemoradiotherapy) given > 4 weeks prior to the beginning of study therapy At least one measurable lesion according to the RECIST criteria. Minimum indicator lesion size: > 10 mm measured by spiral CT or >20mm measured by conventional techniques(Except for Phase I setting). Patients aged between 20 and 75 years, inclusive, at the time of acquisition of informed consent Patients with performance status(ECOG) 0 to 2 Abnormal hematologic values (WBC ≥ 3.5 x 109/L, Hemoglobin ≥ 9.0g/dl, platelet count ≥ 100 x 109/L) Serum cleatinine ≤ 1.5mg/dl Serum bilirubin ≤ 1.5mg/dl. ALT, AST ≤ 2.0 x upper normal limit (or ≤ 3 x upper normal limit in the case of liver metastases) Normal ECG Life expectancy ≥ 3 months Patients who have given written informed consent to participate in this study Exclusion Criteria: Patients with active multiple cancers; or even if the multiple cancers are metachronous, have a disease-free period of less than 5 years (but excluding cancer in situ and skin cancer) (Except for Phase I setting) Serious, uncontrolled, concurrent infection(s) or illness(es) Patients with no serious concurrent complications (such as heart disease, Intestinal pneumonia) Patients with Liver cirrhosis Patients with fresh hemorrhage from the gastrointestinal tract Patients with poorly controlled diabetes or are treated by continuous use of insulin Patients with concurrent psychiatric disease or psychotic symptoms, and judged to have difficulties participating in the study Patients with retention of body fluid(pleural effusion, ascites, pericardial effusion) necessitating treatment Patients with diarrhea (watery stool) Patients with infection, intestinal palsy or intestinal occlusion Patients with brain metastasis Patients with Gilbert syndrome Patients who have experienced serious drug allergy in the past Patients who are pregnant and lactating or hope to become pregnant during the study period Patients with prior Taxan (Paclitaxel, Docetaxel) or CPT-11 treatment Patients with neuropathy ≥ grade 2 Others, patients judged by the investigator or subinvestigator to be inappropriate as subject

Ages Eligible for Study
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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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Paclitaxel+Irinotecan | Drug: Taxol<br>* Day1,15 X mg/m2, IV (in the vein)<br>* Other names: Paclitaxel;Drug: Campt, Topotesin<br>* Day1,15 Y mg/m2, IV (in the vein)<br>* Other names: irinotecan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the DLT(Dose Limiting Toxicity) and MTD(Maximum Tolerated Dose) in Phase I setting. Determine the clinical response rate with Recommended dose in Phase II setting. |  | 1-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the clinical response rate of patients in Phase I setting. |  | 1-year | 
| Determine the MST(Median Survival Time) and PFS(Progression Free Survival) in Phase II setting. |  | 2-years |