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

Gastric Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003298
• Other study ID #: CDR0000066237
• Secondary ID: E7296U10CA023318
• Status: Completed
• Phase: Phase 2
• Start date: June 1, 1999
• Est. completion date: May 2011

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: May 2011
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Gastric Cancer
• Stomach Neoplasms

Intervention

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.
• fluorouracil
Postoperative regimen 5-FU, along with Leucovorin, was given by IV bolus, with 5-FU given immediately after the Leucovorin
• leucovorin calcium
Both 5-FU and Leucovorin will be given via IV bolus, with Leucovorin given immediately before 5-FU.
• 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.

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

Locations

Country	Name	City	State
United States	CCOP - Ann Arbor Regional	Ann Arbor	Michigan
United States	Emory University Hospital - Atlanta	Atlanta	Georgia
United States	New England Medical Center Hospital	Boston	Massachusetts
United States	Albert Einstein Comprehensive Cancer Center	Bronx	New York
United States	CCOP - Cedar Rapids Oncology Project	Cedar Rapids	Iowa
United States	Robert H. Lurie Comprehensive Cancer Center, Northwestern University	Chicago	Illinois
United States	Veterans Affairs Medical Center - Lakeside Chicago	Chicago	Illinois
United States	Ireland Cancer Center	Cleveland	Ohio
United States	CCOP - Colorado Cancer Research Program, Inc.	Denver	Colorado
United States	CCOP - Evanston	Evanston	Illinois
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	Veterans Affairs Medical Center - Indianapolis (Roudebush)	Indianapolis	Indiana
United States	CCOP - Kalamazoo	Kalamazoo	Michigan
United States	CCOP - Marshfield Medical Research and Education Foundation	Marshfield	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Veterans Affairs Medical Center - Milwaukee (Zablocki)	Milwaukee	Wisconsin
United States	Morristown Memorial Hospital	Morristown	New Jersey
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus	Nashville	Tennessee
United States	Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	CCOP - Ochsner	New Orleans	Louisiana
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Raritan Bay Medical Center	Perth Amboy	New Jersey
United States	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania
United States	University of Rochester Cancer Center	Rochester	New York
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Somerset Medical Center	Somerville	New Jersey
United States	CCOP - Toledo Community Hospital Oncology Program	Toledo	Ohio
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	CCOP - MainLine Health	Wynnewood	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
ECOG-ACRIN Cancer Research Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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
Secondary	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