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Irinotecan/Cisplatin, Potentially Curative Surgery With or Without Floxuridine, Followed by Capecitabine for Stomach and Gastro-Esophageal Junction (GEJ) Cancers
This study is currently recruiting participants.
Verified by New York University School of Medicine, February 2009
First Received: February 19, 2009   No Changes Posted
Sponsors and Collaborators: New York University School of Medicine
Food and Drug Administration (FDA)
Information provided by: New York University School of Medicine
ClinicalTrials.gov Identifier: NCT00848783
  Purpose

This study is to determine whether intraperitoneal Floxuridine is effective in the patients with advanced stomach or gastro-esophageal junction cancers in the treatment consisting of pre- and post-surgery chemotherapies.


Condition Intervention Phase
Gastric Cancer
Gastroesophageal Adenocarcinoma
Gastric Adenocarcinoma
Drug: Cisplatin+Irinotecan
Drug: Floxuridine
Drug: Capecitabine
Phase II

Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
Official Title: A Randomized Phase-II Study of Patients With Locally Advanced Gastric of Gastro-Esophageal Adenocarcinoma Treated With Induction Irinotecan/Cisplatin, Potentially Curative Surgery With or Without Adjuvant Intraperitoneal Floxuridine, Followed by Prolonged Administration of Capecitabine

Resource links provided by NLM:


Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:
  • one-year recurrence-free survival rate [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • overall survival rate; toxicity; evaluation of sites of relapse of failing patients [ Time Frame: every 4 months for the first 2 years, every 6 months for years 3 and 4, then every 12 months for up to 10 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 62
Study Start Date: May 2008
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
A: Experimental

with Floxuridine

Induction treatment:

Day 1,8,15,22: Cisplatin 25 mg/M2/week; Day 1,8,15,22: Irinotecan 75 mg/M2/week, both intravenous; Two weeks without treatment; Repeat the course with or without cisplatin/Irinotecan dose modification. If clinical PD, re-evaluation, and the patient may go off the protocol.

Re-evaluation, surgery if CR, PR or SD, or off the protocol if PD.

BEFORE SURGERY: RANDOMIZATION TO ARM A OR B

Surgery. The intraperitoneal (ip) catheter for ARM A in place.

Postoperative treatment starts 1-3 weeks after the surgery.

Postoperative ip treatment:

Day 1,2,3:Floxuridine 3 gm/day, Intraperitoneal; Day 3:Cisplatin 60 mg/M2, Intraperitoneal; 2 weeks without treatment;

Day 22,23,24:Floxuridine 3 gm/day, Intraperitoneal; Day 24:Cisplatin 60 mg/M2, Intraperitoneal; 1 week without treatment.

Postoperative systemic treatment:

course 1-9:Capecitabine 2,000 mg/M2/day x14 q 3 weeks/course, Oral

Drug: Cisplatin+Irinotecan
Cisplatin+Irinotecan
Drug: Floxuridine
Floxuridine
Drug: Capecitabine
Capecitabine
B: Experimental

without Floxuridine

Same as Arm A except that no postoperative IP treatment.

Drug: Cisplatin+Irinotecan
Cisplatin+Irinotecan
Drug: Capecitabine
Capecitabine

Detailed Description:

A previous Phase-II trial conducted by the same principle investigator(s), utilizing preoperative chemotherapy and intraperitoneal (IP) consolidation, was conducted in patients with locally advanced, potentially resectable gastric cancer or cancer of the gastro-esophageal junction (GEJ), both staged as T3N0, T4N0, any TN1 or TN2 disease. The data suggest that for patients with locally advanced gastric or GEJ cancer, systemic induction therapy, curative surgery with high Ro resection rates, and IP adjuvant therapy, has acceptable toxicity and encouraging survival outcome. The Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial has also shown that perioperative chemotherapy - chemotherapy given both before and after surgery - can provide a significant survival benefit.

The investigators hypothesize that adjuvant intraperitoneal(IP)salvage of cancer micrometastatic residues after surgery contributes to disease-free survival. The goal of this trial is to determine whether IP Floxuridine, added to adjuvant postoperative chemotherapy, prolongs patient's survival. This will be tested during the randomized open-label trial.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Only untreated patients with histologically documented gastric/GEJ adenocarcinoma, clinical AJCC stage grouping (11) IB-IV (Mo) by CT scan and laparoscopy/endoscopic ultrasound, are eligible.
  • Both men and women >18 years of age with ECOG performance status 0-2, members of any ethnic group and minorities.
  • Patients without another invasive malignancy, with adequately treated basal cell or squamous cell skin cancer, free for 5 years or more of in-situ cervix cancer or other in-situ cancer.
  • An adequate bone-marrow reserve (absolute neutrophil count >1,500/ mmL, thrombocytes >100,000 mmL, hemoglobin >9 gm/dL).
  • Preserved liver and renal function (total serum bilirubin <2 mg/dL, SGOT/SGPT <3x the upper limit of normal, alkaline phosphatase <3x the upper limit of normal, BUN <30 mg/dL, serum creatinine concentration <1.5 mg/dL and creatinine clearance >50 mL/min) are required. Creatinine clearance should be normalized for 1.73 M2 BSA.. The prothrombin time, activated partial thromboplastin time, and thrombin time should be within the range of normal values.
  • No prior severe reaction to fluoropyrimidine therapy or known hypersensitivity to 5-FU. Capecitabine (Xeloda) is contraindicated in patients with severe renal impairment, i.e., creatinine clearance below 30 mL/min, determined by Cockroft-Gault equation shown on page 15 under (i) Renal impairment. In patients with moderate renal impairment (creatinine clearance 30-50 mL/min), which develops during the course of adjuvant treatment with Capecitabine, the drug is decreased to 75% of the starting dose.
  • Patients who signed written informed consent as this is specified in section 4. Registration Procedures of the study protocol.

Exclusion Criteria

  • Patients in need of urgent surgery for gastro-intestinal obstruction, perforation or hemorrhage
  • Since immune deficiency increases the risk of terminal infections when aggravated by bone marrow suppressive therapy, patients with active or uncontrolled infection including HIV are excluded.
  • Patients with psychiatric disorders that may interfere with their consent and/or with protocol follow-up.
  • Since chemotherapeutic agents to be used are known or suspected to be teratogenic or with other adverse effects, women must not be pregnant or breast-feeding. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy. All patients of reproductive age may not participate unless they agree to use an effective medically acceptable contraceptive method.
  • Patients with diagnosed Gilbert's disease and bilirubin level >2.0 mg/dL, as these patients may have excessive CPT-11 toxicity.
  • Patients with any severe concurrent disease, such as cardiac condition not responding to medication, myocardial infarction within the last 12 months, active infection or uncontrolled pulmonary disease, or any other disease which in judgment of the investigator would make the patient inappropriate for entry into this study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00848783

Contacts
Contact: Franco Muggia, MD 212-263-6485 franco.muggia@nyumc.org
Contact: Minerva Utate, RN 212-263-5926 minerva.utate@nyumc.org

Locations
United States, California
Norris Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Syma Iqbal, MD     323-865-3907        
United States, New York
NYU Cancer Center Recruiting
New York, New York, United States, 10016
Bellevue Hospital Recruiting
New York, New York, United States, 10016
Peru
INEN Recruiting
Lima, Peru
Contact: Jorge Chong, MD     511-620-4995     eruiz@inen.sld.pe    
Sponsors and Collaborators
New York University School of Medicine
Food and Drug Administration (FDA)
Investigators
Principal Investigator: Franco Muggia, MD New York University School of Medicine
  More Information

No publications provided

Responsible Party: New York University Cancer Institute ( Franco Muggia, MD )
Study ID Numbers: 07-837, NYU 05-20
Study First Received: February 19, 2009
Last Updated: February 19, 2009
ClinicalTrials.gov Identifier: NCT00848783     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by New York University School of Medicine:
gastric cancer
gastroesophageal junction
stomach cancer
intraperitoneal infusion
capecitabine
irinotecan
cisplatin
floxuridine

Study placed in the following topic categories:
Antimetabolites
Capecitabine
Digestive System Neoplasms
Floxuridine
Gastrointestinal Diseases
Irinotecan
Adjuvants, Immunologic
Carcinoma
Digestive System Diseases
Stomach Diseases
Radiation-Sensitizing Agents
Cisplatin
Esophageal Disorder
Stomach Neoplasms
Gastrointestinal Neoplasms
Esophageal Diseases
Stomach Cancer
Adenocarcinoma
Antineoplastic Agents, Phytogenic
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Diseases
Antineoplastic Agents
Irinotecan
Physiological Effects of Drugs
Stomach Diseases
Neoplasms by Site
Cisplatin
Stomach Neoplasms
Therapeutic Uses
Capecitabine
Digestive System Neoplasms
Neoplasms by Histologic Type
Floxuridine
Enzyme Inhibitors
Pharmacologic Actions
Carcinoma
Neoplasms
Digestive System Diseases
Radiation-Sensitizing Agents
Gastrointestinal Neoplasms
Adenocarcinoma
Antineoplastic Agents, Phytogenic
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on August 30, 2009