Phase I Study of Interperitoneal Chenotherapy in Patients With Gastric Adenocarainoma With Peritoneal Seeding
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of Interperitoneal Chenotherapy in Patients With Gastric Adenocarainoma With Peritoneal Seeding|
- 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. [ Time Frame: 3 years ]
|Study Start Date:||October 2004|
|Study Completion Date:||August 2007|
|Primary Completion Date:||December 2006 (Final data collection date for primary outcome measure)|
Postoperative day 1, IP CPT-11 chemotherapy will be given by CAPD catheter. CPT-11 in 1L of normal saline, prewarmed to 37°C will be given intraperitoneally.
If there is no DLT and patients agree with the treatment, patients can receive 3 more times of IP chemotherapy with same dose of CPT-11 at 3 weeks interval. After total 4 cycles of IP chemotherapy, peritoneal disease will be reassessed with abdominal-pelvis CT. Pharmacokinetic study is not planned with this treatment.
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)
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).
Please refer to this study by its ClinicalTrials.gov identifier: NCT00539877
|Korea, Republic of|
|Samsung Medical Center|
|Seoul, Korea, Republic of, 135-710|
|Principal Investigator:||Young Suk Park, M.D.,Ph.D.||Samsung Medical Center, Seoul, Korea|