Irinotecan/Cisplatin, Potentially Curative Surgery With or Without Floxuridine, Followed by Capecitabine for Stomach and Gastro-esophageal Junction (GEJ) Cancers - Full Text View

Purpose

This study is to determine whether intraperitoneal (IP) 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 Gastric Adenocarcinoma Esophageal Cancer	Drug: Irinotecan Drug: Cisplatin Procedure: Surgery Drug: Floxuridine Drug: Capecitabine	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
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:

MedlinePlus related topics: Cancer Esophageal Cancer Esophagus Disorders Stomach Cancer

Drug Information available for: Floxuridine Cisplatin Irinotecan Irinotecan hydrochloride Capecitabine

U.S. FDA Resources

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

Primary Outcome Measures:

Number of Patients With One-year Recurrence-free Survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
This is defined as the patients who did not have recurrence of cancer at 1 year since the start of induction chemotherapy.

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 ]

Enrollment:	8
Study Start Date:	May 2008
Study Completion Date:	September 2012
Primary Completion Date:	August 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: A-with IP Floxuridine Induction treatment: Cisplatin 25 mg/m^2 and Irinotecan 75 mg/m^2 once a week for 4 weeks, both intravenous; Two weeks without treatment; Repeat the course once. Re-evaluation, surgery if complete response, partial response or stable disease, or off the protocol if progression of disease. Randomization Surgery. Postoperative IP treatment: Day 1,2,3: Floxuridine 3 gm/day, IP; Day 3: Cisplatin 60 mg/m^2, IP; 2 weeks without treatment; repeat the course once Postoperative systemic treatment: courses 1-9: Capecitabine 2,000 mg/m^2/day x14 every 3 weeks/course, Oral	Drug: Irinotecan Other Name: CPT-11 Drug: Cisplatin Procedure: Surgery Drug: Floxuridine Other Name: FUDR Drug: Capecitabine Other Name: Xeloda
Experimental: B-Without IP Floxuridine Same as Arm A except no postoperative IP treatment.	Drug: Irinotecan Other Name: CPT-11 Drug: Cisplatin Procedure: Surgery Drug: Capecitabine Other Name: Xeloda

Arms

Assigned Interventions

Experimental: A-with IP Floxuridine

Induction treatment:

Cisplatin 25 mg/m^2 and Irinotecan 75 mg/m^2 once a week for 4 weeks, both intravenous; Two weeks without treatment; Repeat the course once.
Re-evaluation, surgery if complete response, partial response or stable disease, or off the protocol if progression of disease.
Randomization
Surgery.
Postoperative IP treatment:

Day 1,2,3: Floxuridine 3 gm/day, IP; Day 3: Cisplatin 60 mg/m^2, IP; 2 weeks without treatment; repeat the course once
Postoperative systemic treatment: courses 1-9: Capecitabine 2,000 mg/m^2/day x14 every 3 weeks/course, Oral

Drug: Irinotecan

Other Name: CPT-11

Drug: Cisplatin Procedure: Surgery Drug: Floxuridine

Other Name: FUDR

Drug: Capecitabine

Other Name: Xeloda

Experimental: B-Without IP Floxuridine

Same as Arm A except no postoperative IP treatment.

Drug: Irinotecan

Other Name: CPT-11

Drug: Cisplatin Procedure: Surgery Drug: Capecitabine

Other Name: Xeloda

Detailed Description:

A previous Phase-II trial conducted by the same principle investigator(s), utilizing preoperative chemotherapy and intraperitoneal 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 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

Only untreated patients with histologically documented gastric/GEJ adenocarcinoma, clinical American Joint Committee on Cancer (AJCC) stage grouping (11) IB-IV (Mo) by CT scan and laparoscopy/endoscopic ultrasound, are eligible. Excluded are patients in need of urgent surgery for gastro-intestinal obstruction, perforation or hemorrhage.
Both men and women >= 18 years of age with Eastern Cooperative Oncology Group (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.
Since immune deficiency increases the risk of terminal infections when aggravated by bone marrow suppressive therapy, patients must be without active or uncontrolled infection including HIV.
Patients without psychiatric disorders that may interfere with their consent and/or with protocol follow-up.
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, blood urea nitrogen (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 M^2 BSA. The prothrombin time, activated partial thromboplastin time, and thrombin time should be within the range of normal values.
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 without diagnosed Gilbert's disease and bilirubin level >= 2.0 mg/dL, as these patients may have excessive CPT-11 toxicity.
No prior severe reaction to fluoropyrimidine therapy or known hypersensitivity to 5-fluorouracil. Capecitabine (Xeloda) is contraindicated in patients with severe renal impairment, i.e., creatinine clearance below 30 mL/min, determined by Cockcroft-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 should be without 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.
Patients who signed written informed consent.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00848783

Locations

United States, California
Norris Cancer Center
Los Angeles, California, United States, 90033
United States, New York
NYU Cancer Center
New York, New York, United States, 10016
Bellevue Hospital
New York, New York, United States, 10016

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:	Franco Muggia, MD, New York University Cancer Institute
ClinicalTrials.gov Identifier:	NCT00848783 History of Changes
Other Study ID Numbers:	07-837, NYU 05-20
Study First Received:	February 19, 2009
Results First Received:	November 9, 2012
Last Updated:	December 10, 2012
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

Additional relevant MeSH terms:

Adenocarcinoma
Adenocarcinoma, Mucinous
Esophageal Diseases
Esophageal Neoplasms
Stomach Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Cystic, Mucinous, and Serous
Gastrointestinal Diseases
Digestive System Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site

Head and Neck Neoplasms
Stomach Diseases
Irinotecan
Capecitabine
Cisplatin
Floxuridine
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 16, 2013