Chemotherapy, Surgery, and Radiation Therapy in Treating Patients With Gastric Cancer

A Phase II Trial of Neoadjuvant Paclitaxel - Cisplatin Chemotherapy, Surgery and Adjuvant Radiation Therapy and 5-FU/Leucovorin for Gastric Cancer

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy, radiation therapy, and surgery may kill more tumor cells. E7296 was conducted to study neoadjuvant chemotherapy and postoperative chemoradiation therapy in patients diagnosed with high-risk gastric cancer using a new neoadjuvant regimen: paclitaxel plus cisplatin. It was hypothesized that this new neoadjuvant chemotherapy followed by surgery and chemoradiation therapy would be well tolerated and would have a high curative resection rate.

Study Overview

• Status: Completed
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: cisplatin; Drug: fluorouracil; Drug: leucovorin calcium; Drug: paclitaxel; Procedure: surgery; Radiation: radiation therapy

Detailed Description

OBJECTIVES:

Primary objective: To evaluate the tolerability and toxicity of neoadjuvant cisplatin plus paclitaxel and postoperative chemoradiation therapy with fluorouracil plus leucovorin calcium in patients with high-risk gastric cancer.

Secondary objectives: To assess the pathologic response of gastric tumors to neoadjuvant cisplatin plus paclitaxel chemotherapy, and preliminarily assess the patterns of failure and disease free and overall survival.

OUTLINE: Patients receive 3 courses of preoperative neoadjuvant chemotherapy given on day 1 every 21 days. Courses consist of an intravenous infusion of cisplatin and a 3 hour intravenous infusion of paclitaxel on day 1. Patients then undergo surgery for tumor removal on day 63, followed 4-6 weeks later by one course of daily intravenous bolus leucovorin calcium and fluorouracil for 5 days. Chemotherapy is repeated 4-6 weeks later for the first 4 days of week 1 and the last 3 days of week 5 of radiation therapy given 5 days a week for 5 weeks. Patients receive two more courses, 4 weeks apart, of fluorouracil and leucovorin calcium for 5 days 4-6 weeks after completing radiation treatment. Patients are followed every month for the first 3 months, every 3 months for the next 21 months, every 6 months for the next year, and annually thereafter.

PROJECTED ACCRUAL: Approximately 30-42 patients will be accrued over 18 months.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80209-5031
      • CCOP - Colorado Cancer Research Program, Inc.
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital - Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60611-3013
      • Robert H. Lurie Comprehensive Cancer Center, Northwestern University
    • Chicago, Illinois, United States, 60611
      • Veterans Affairs Medical Center - Lakeside Chicago
    • Evanston, Illinois, United States, 60201
      • CCOP - Evanston
    • Urbana, Illinois, United States, 61801
      • CCOP - Carle Cancer Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5289
      • Indiana University Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • Veterans Affairs Medical Center - Indianapolis (Roudebush)
  • Iowa
    • Cedar Rapids, Iowa, United States, 52403-1206
      • CCOP - Cedar Rapids Oncology Project
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • CCOP - Ochsner
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • New England Medical Center Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • CCOP - Ann Arbor Regional
    • Kalamazoo, Michigan, United States, 49007-3731
      • CCOP - Kalamazoo
  • Minnesota
    • Saint Louis Park, Minnesota, United States, 55416
      • CCOP - Metro-Minnesota
  • Nebraska
    • Omaha, Nebraska, United States, 68131
      • CCOP - Missouri Valley Cancer Consortium
  • New Jersey
    • Morristown, New Jersey, United States, 07962-1956
      • Morristown Memorial Hospital
    • New Brunswick, New Jersey, United States, 08901
      • Cancer Institute of New Jersey
    • Perth Amboy, New Jersey, United States, 08861
      • Raritan Bay Medical Center
    • Somerville, New Jersey, United States, 08876
      • Somerset Medical Center
  • New York
    • Bronx, New York, United States, 10461
      • Albert Einstein Comprehensive Cancer Center
    • Rochester, New York, United States, 14642
      • University of Rochester Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44106-5065
      • Ireland Cancer Center
    • Toledo, Ohio, United States, 43623-3456
      • CCOP - Toledo Community Hospital Oncology Program
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-4283
      • University of Pennsylvania Cancer Center
    • Wynnewood, Pennsylvania, United States, 19096
      • CCOP - MainLine Health
  • Tennessee
    • Nashville, Tennessee, United States, 37232-6838
      • Vanderbilt-Ingram Cancer Center
    • Nashville, Tennessee, United States, 37212
      • Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus
  • Wisconsin
    • Marshfield, Wisconsin, United States, 54449
      • CCOP - Marshfield Medical Research and Education Foundation
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
    • Milwaukee, Wisconsin, United States, 53295
      • Veterans Affairs Medical Center - Milwaukee (Zablocki)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction
• Localized cancer that is potentially curable by surgery (T2, N1-2, M0 or T3-4, any N, M0)
• No metastatic cancer to the ovaries
• Age: 18 and over
• Easter Cooperative Oncology Group (ECOG) performance status 0-2
• White blood cell (WBC) count at least 4,000 cells/mm3
• Platelet count at least 150,000/mm3
• Bilirubin less than 2 mg/dL
• Creatinine no greater than 1.5 mg/dL
• Creatinine clearance greater than 50 mL/min
• Caloric intake must be at least 1500 kcal/day
• No prior history of cancer within the past 5 years except for basal cell carcinoma of the skin or in situ carcinoma of the cervix
• No prior radiation therapy, except for skin cancer
• Fertile patients must use adequate contraception

• Met criteria for re-registration after surgery

  • T1N1-2M0, T2N1-2M0 or T3-4NanyM0 at time of initial re-registration.
  • No evidence of metastatic disease from postoperative pathologic staging.
  • ECOG performance status of 0, 1, or 2 at re-registration
  • Curative resection performed
  • Re-registered 4 - 6 weeks from the date of surgery
  • WBC ≥ 4000 cells/mm³, platelets ≥ 150,000/mm³, creatinine ≤ 1.5 mg/dl or creatinine clearance of > 50 ml/min (measured or calculated) and total serum bilirubin < 2 mg/dl, all within four weeks prior to re-registration

Exclusion Criteria:

• Prior chemotherapy
• Clinically significant auditory impairment
• Significant heart disease
• Pregnant or lactating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Experimental Arm; Patients receive 3 courses of preoperative neoadjuvant chemotherapy given on day 1 every 21 days. Courses consist of an intravenous infusion of cisplatin and a 3 hour intravenous infusion of paclitaxel on day 1. Patients then undergo surgery for tumor removal on day 63, followed 4-6 weeks later by one course of daily intravenous bolus leucovorin calcium and fluorouracil for 5 days. Chemotherapy is repeated 4-6 weeks later for the first 4 days of week 1 and the last 3 days of week 5 of radiation therapy given 5 days a week for 5 weeks. Patients receive two more courses, 4 weeks apart, of fluorouracil and leucovorin calcium for 5 days 4-6 weeks after completing radiation treatment.

Drug: cisplatin; Cisplatin was administered as part of the neoadjuvant regimen. It was given at a dose of 75 mg/m² via IV over approximately one hour, on day 1 of each cycle. Three cycles were given.; Other Names: CDDP; Platinol; platinum; DDP; Platinol-AQ; DACP; cis-platinum; cisdiamminedichloroplatinum (II); Drug: fluorouracil; Postoperative regimen 5-FU, along with Leucovorin, was given by IV bolus, with 5-FU given immediately after the Leucovorin; Other Names: 5-FU; 5-Fluorouracil; Adrucil; Efudex; Drug: leucovorin calcium; Both 5-FU and Leucovorin will be given via IV bolus, with Leucovorin given immediately before 5-FU.; Other Names: LV; Leucovorin; LCV; Wellcovorin; citrovorum factor; folinic acid; 5-formyl tetrahydrofolate; Drug: paclitaxel; Paclitaxel was administered as part of the neoadjuvant regimen. It was given at a dose of 175 mg/m² as a 3 hour continuous intravenous infusion on day 1. Three cycles were given.; Other Names: Taxol®; NSC 125973; Procedure: surgery; The surgical procedure performed involved a radical subtotal or total gastrectomy. A complete surgical resection was required; Radiation: radiation therapy; Concomitant chemotherapy and radiation therapy course: 5-FU 400 mg/m²/day + Leucovorin 20 mg/m²/day on days 1-4 of week one and days 1-3 of week 5 of XRT. Combined chemotherapy and radiation therapy were to begin 4 weeks after day 1 of the initial course of chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Grade 3 or Higher Toxicity Incidence on Step 1	Incidence is defined as proportion of patients with any grade 3 or higher treatment-related toxicities among all treated patients.	assessed at the end of every cycle (cycle=21 days) during treatment (3 cycles in total)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Confirmed Response to Neoadjuvant Therapy	Response was based on pathology at surgery. A patient achieved complete response if no gross or microscopic tumor were identified with the surgical specimen and nodal tissue. Stable response was defined as a response that did not qualify as complete response or progressive disease (PD), where PD indicated metastatic spread. Best confirmed response rate was defined as the proportion of patients with complete response (CR). A patient was considered unevaluable if the patient did not have surgery, the pathologist did not examine at least 15 lymph nodes, or the pathology report was unavailable.	Assessed at surgery time (surgery performed during week 8-10 after registration to the study)
Overall Survival	Overall survival was defined as the time from registration to death, where a subject was censored on date of last record alive.	assessed every month for the first 3 months, every 3 months for the next 21 months, every 6 months for the next year, and annually thereafter up to year 10
Progression Free Survival	Progression-free survival (PFS) was defined as time from registration until progression, recurrence, or death, whichever occurred first. If date of death occurred beyond three months from the date of last disease assessment, then PFS was censored at date of last disease assessment. Patients who were alive and progression-free were censored at the date of last disease evaluation.	assessed every month for the first 3 months, every 3 months for the next 21 months, every 6 months for the next year, and annually thereafter up to year 10

Collaborators and Investigators

• Sponsor: ECOG-ACRIN Cancer Research Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: David I. Rosenthal, MD, Abramson Cancer Center at Penn Medicine

Publications and helpful links

General Publications

• Chakravarthy AB, Catalano PJ, Mondschein JK, Rosenthal DI, Haller DG, Whittington R, Spitz FR, Wagner H, Sigurdson ER, Tschetter LK, Bayer GK, Mulcahy MF, Benson AB. Phase II Trial of Paclitaxel/Cisplatin Followed by Surgery and Adjuvant Radiation Therapy and 5-Fluorouracil/Leucovorin for Gastric Cancer (ECOG E7296). Gastrointest Cancer Res. 2012 Nov;5(6):191-7.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 1999
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: January 22, 2004
• First Posted (Estimated): January 23, 2004

Study Record Updates

• Last Update Posted (Actual): July 6, 2023
• Last Update Submitted That Met QC Criteria: June 21, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: stage IV gastric cancer; stage III gastric cancer; adenocarcinoma of the stomach; stage II gastric cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protective Agents; Antineoplastic Agents, Phytogenic; Micronutrients; Vitamins; Calcium-Regulating Hormones and Agents; Antidotes; Vitamin B Complex; Paclitaxel; Cisplatin; Fluorouracil; Leucovorin; Calcium; Levoleucovorin; Tetrahydrofolates; Formyltetrahydrofolates
• Other Study ID Numbers: CDR0000066237; U10CA023318 (U.S. NIH Grant/Contract); E7296 (Other Identifier: Eastern Cooperative Oncology Group); NCT00003298 (Registry Identifier: National Cancer Institute)