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

NCT00539877 | Completed Phase 1 DMC

• 1 other identifier: 2004-05-017
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

Stomach cancer is the most common cancer, and is still leading cause of death in Korea. Peritoneal seeding is the most common metastases of gastric cancer, and is the most frequent cause of death from this disease. In addition, there is no standard treatment for peritoneal dissemination. Even though systemic intravenous chemotherapy is the standard treatment for metastatic stomach cancer at present, it does not improve the survival of patients with peritoneal dissemination. Because intraperitoneal(IP) administration results in high concentration locally with low systemic toxicity, clinical investigators have confirmed the safety and pharmacokinetic advantage associated with IP delivery of a number of antineoplastic agents with known activity in cancer. In ovarian cancer, a large randomized trial demonstrated a small but statistically and clinically significant survival advantage for women receiving a portion of their therapy intraperitoneally. Drugs such as 5-fluorouracil, cisplatin, mitomycin-C, paclitaxel and docetaxel are used for IP chemotherapy in patients with gastric cancer. Even the small number of phase III trials reported, some studies showed improvement in survival for patients randomized to IP therapy compared to those receiving no postoperative treatment. Irinotecan(7-ethyl-10-\[4-(1-pipperidino)-1-piperidino\] carbonyloxy camptothecin; CPT-11), clinically effective in the treatment of colorectal, lung and gastric cancer, is a carbamate prodrug metabolized to its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38). In mouse model, IP administration of CPT-11 was significantly more effective than intravenous administration for control of both peritoneal seeding and liver metastasis. However, phamacokinetics of CPT-11 with peritoneal administration in human beings is not well studied. Although Japanese investigators reported pharmacokinetic data of CPT-11 with few patients, there is no data about maximum tolerated dose of CPT-11 intraperitoneally.

Conditions

Stomach Neoplasms

Keywords

Gstric cancer; Pritoneal seeding; Intraperitoneal chemotherapy; Irinotecan

Outcome Measures

Primary Outcomes (1)

• 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.

  3 years

Interventions

irinotecan DRUG

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologic diagnosis of gastric adenocarcinoma
• Preoperative studies of resectable disease; endoscopic finding of advanced gastric cancer, radiologic finding of T3 or T4 disease with or without suspicious peritoneal seeding
• Males or females at least 18 years of age
• Performance status 0-1 on the ECOG criteria
• The operative finding and biopsy of suspected peritoneum must show peritoneal involvement of adenocarcinoma
• No previous chemotherapy, immunotherapy or radiotherapy
• No biological major abnormalities.
• Adequate hematologic (WBC count ≥ 4,000/mm3, platelet count ≥ 150,000/mm3), hepatic (bilirubin level £ 1.5 mg/dL), and renal (creatinine concentration £ 1.5 mg/dL) function.
• Informed consent from patient or patient's relative
• If female: childbearing potential either terminated by surgery, radiation, or menopause, or attenuated by use of an approved contraceptive method (intrauterine device \[IUD\], birth control pills, or barrier device) during and for 3 months after trial. If male, use of an approved contraceptive method during the study and 3 months afterwards

You may not qualify if:

• Myocardial infarction within preceding 6 months or symptomatic heart disease, including unstable angina, congestive heart failure or uncontrolled arrhythmia
• Serious concomitant infection
• Second primary malignancy (except in situ carcinoma of the cervix or adequately treated basal cell carcinoma of the skin or prior malignancy treated more than 5 years ago without recurrence)
• History of significant neurologic or psychiatric disorders
• Pregnant or lactating women
• Women of child bearing potential not using a contraceptive method

Sponsors & Collaborators

• Samsung Medical Center: lead

Study Sites (1)

Samsung Medical Center

Seoul, 135-710, South Korea

Location

Related Publications (4)

• Guichard S, Chatelut E, Lochon I, Bugat R, Mahjoubi M, Canal P. Comparison of the pharmacokinetics and efficacy of irinotecan after administration by the intravenous versus intraperitoneal route in mice. Cancer Chemother Pharmacol. 1998;42(2):165-70. doi: 10.1007/s002800050801.

  PMID: 9654118 RESULT

• Maruyama M, Nagahama T, Yuasa Y. Intraperitoneal versus intravenous CPT-11 for peritoneal seeding and liver metastasis. Anticancer Res. 1999 Sep-Oct;19(5B):4187-91.

  PMID: 10628373 RESULT

• Rosen HR, Jatzko G, Repse S, Potrc S, Neudorfer H, Sandbichler P, Zacherl J, Rabl H, Holzberger P, Lisborg P, Czeijka M. Adjuvant intraperitoneal chemotherapy with carbon-adsorbed mitomycin in patients with gastric cancer: results of a randomized multicenter trial of the Austrian Working Group for Surgical Oncology. J Clin Oncol. 1998 Aug;16(8):2733-8. doi: 10.1200/JCO.1998.16.8.2733.

  PMID: 9704725 RESULT

• Rothenberg ML, Liu PY, Braly PS, Wilczynski SP, Hannigan EV, Wadler S, Stuart G, Jiang C, Markman M, Alberts DS. Combined intraperitoneal and intravenous chemotherapy for women with optimally debulked ovarian cancer: results from an intergroup phase II trial. J Clin Oncol. 2003 Apr 1;21(7):1313-9. doi: 10.1200/JCO.2003.07.031.

  PMID: 12663720 RESULT

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Irinotecan

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Young Suk Park, M.D.,Ph.D.

  Samsung Medical Center, Seoul, Korea

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 3, 2007
• First Posted: October 5, 2007
• Study Start: October 1, 2004
• Primary Completion: December 1, 2006
• Study Completion: August 1, 2007
• Last Updated: June 23, 2010

Record last verified: 2010-06

Locations

KR (1)