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

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group )
ClinicalTrials.gov Identifier:
NCT00003298
First received: November 1, 1999
Last updated: June 22, 2015
Last verified: June 2015
  Purpose
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.

Condition Intervention Phase
Gastric Cancer
Drug: cisplatin
Drug: fluorouracil
Drug: leucovorin calcium
Drug: paclitaxel
Procedure: surgery
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Neoadjuvant Paclitaxel - Cisplatin Chemotherapy, Surgery and Adjuvant Radiation Therapy and 5-FU/Leucovorin for Gastric Cancer

Resource links provided by NLM:


Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • Grade 3 or Higher Toxicity Incidence on Step 1 [ Time Frame: assessed at the end of every cycle (cycle=21 days) during treatment (3 cycles in total) ] [ Designated as safety issue: Yes ]
    Incidence is defined as proportion of patients with any grade 3 or higher treatment-related toxicities among all treated patients.


Secondary Outcome Measures:
  • Best Confirmed Response to Neoadjuvant Therapy [ Time Frame: Assessed at surgery time (surgery performed during week 8-10 after registration to the study) ] [ Designated as safety issue: No ]
    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.

  • Overall Survival [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Overall survival was defined as the time from registration to death, where a subject was censored on date of last record alive.

  • Progression Free Survival [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 39
Study Start Date: February 1999
Study Completion Date: May 2011
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • Platinol
  • cis-platinum
  • cisdiamminedichloroplatinum (II)
  • Platinol-AQ
  • DACP
  • platinum
  • CDDP
  • DDP
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-Fluorouracil
  • 5-FU
  • 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:
  • Leucovorin
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • 5-formyl tetrahydrofolate
  • LV
  • LCV
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003298

  Show 30 Study Locations
Sponsors and Collaborators
ECOG-ACRIN Cancer Research Group
National Cancer Institute (NCI)
Investigators
Study Chair: David I. Rosenthal, MD Abramson Cancer Center of the University of Pennsylvania
  More Information

Publications:
Responsible Party: ECOG-ACRIN Cancer Research Group
ClinicalTrials.gov Identifier: NCT00003298     History of Changes
Other Study ID Numbers: CDR0000066237  E7296  U10CA023318 
Study First Received: November 1, 1999
Results First Received: June 2, 2015
Last Updated: June 22, 2015
Health Authority: United States: Federal Government

Keywords provided by Eastern Cooperative Oncology Group:
stage II gastric cancer
stage III gastric cancer
stage IV gastric cancer
adenocarcinoma of the stomach

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Cisplatin
Fluorouracil
Calcium, Dietary
Levoleucovorin
Leucovorin
Tetrahydrofolates
Formyltetrahydrofolates
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Bone Density Conservation Agents
Physiological Effects of Drugs
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Antidotes

ClinicalTrials.gov processed this record on September 28, 2016