Trial Information

Phase I Study of Interperitoneal Chenotherapy in Patients With Gastric Adenocarainoma With Peritoneal Seeding

Objectives : The objectives of this study are to assess the feasibility, to determine the
maximum tolerated dose, and to assess the toxicities of intraperitoneally administered
CPT-11 in gastric cancer patients with peritoneal seeding.

Methods : This is open-labeled, non-randomized phase I study in the patients eligible for
the following criteria. Patients more than 18 years old with gastric adenocarcinoma,
histologically proven, will be enrolled at the time of surgery, and the signed informed
consent will be obtained prior to surgery. Preoperative studies should have resectable
advanced disease. The operative finding and biopsy of suspected peritoneum must show
peritoneal involvement of adenocarcinoma. The subjects should not have any previous
chemotherapy, immunotherapy or radiotherapy and any major biological abnormalities. Prior to
the initiation of study, patient will receive palliative gastrectomy(total or subtotal) and
has a CAPD catheter. Postoperative day 1, IP chemotherapy will be given by CAPD catheter.
For dose level 1, CPT-11(provided by CJ Pharmaceutical Company) 50mg/m2 in 1L of normal
saline, prewarmed to 37°C will be given intraperitoneally. Plasma samples will be collected
prior IP chemotherapy, and samples of plasma, peritoneal fluid and urine will be obtained at
0.5, 1.5, 2, 3.5, 8, 12, and 25.5, 49, 56 hours following chemotherapy. Three patients will
be accrued to each dose level. If none of these three patients experienced a dose-limiting
toxicity (DLT), the dose will be increased in a subsequent group of three patients to 100
mg/m2.If one of the first three patients experienced DLT, three more patients will be
accrued to that dose level. If none of these additional three patients experienced DLT, then
the dose will be escalated. If one of the additional three patients experienced DLT, then
either an additional cohort of patients could be added or escalation terminated. If two or
more of the second group of three patients experienced DLT, then accrual is stopped. If two
of the first three patients experienced DLT, then an additional three patients could be
accrued at that dose level, but dose escalation could take place only if none of the
additional cohort experienced DLT. The last planned dose escalation is to 300 mg/m2. Cohorts
of at least 3 patients will be entered at each dose level and monitored for at least 4 weeks
after treatment before dose escalation. Intrapatient dose escalation is not permitted.

Dose level Dose of IP CPT-11(mg/m2)

1. 50

2. 100

3. 150

4. 200

5. 300

In this study, DLT is defined as follows: any grade 4 non-hematologic toxicity or as noted
below; ≥ grade 3 diarrhea or stomatitis lasting ≥ 7 days despite optimal supportive care;
hematologic dose-limiting toxicity is defined grade 4 neutropenia complicated by fever ≥
38°C; grade 4 hemorrhage or thrombocytopenia; failure to recover neutrophils (≥ 1500/ mm3)
or platelets (≥ 100 000/ mm3) by day 28. The maximal tolerated dose is defined as that dose
level that produced dose-limiting toxicity in ≥ 50% of patients. The recommended dose is one
level below that. During the study, the evaluation of toxicities will be done daily of
postoperative 6 days then weekly using National Cancer Institute-Common Toxicity Criteria
(NCI-CTC). Physical examination, complete blood count, and blood chemistry, and serum
electrolytes will be measured. Pharmacokinetic study : Plasma, peritoneal fluid and urine
samples will be assayed for irinotecan and its metabolites: SN-38,
7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino] carbonyl camptothecin (APC), and SN-38
glucuronide(SN-38G).