Clinical trial NCT00003298: Chemotherapy, Surgery, and Radiation Therapy in Treating Patients With Gastric Cancer
Official title: A Phase II Trial of Neoadjuvant Paclitaxel - Cisplatin Chemotherapy, Surgery and Adjuvant Radiation Therapy and 5-FU/Leucovorin for Gastric Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastric Cancer
Keywords: stage II gastric cancer
stage III gastric cancer
stage IV gastric cancer
adenocarcinoma of the stomach
Lead sponsor: Eastern Cooperative Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-01-23
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Grade 3 or Higher Toxicity Incidence on Step 1
timeFrame: assessed at the end of every cycle (cycle=21 days) during treatment (3 cycles in total)
Secondary outcomes:
measure: Best Confirmed Response to Neoadjuvant Therapy
timeFrame: Assessed at surgery time (surgery performed during week 8-10 after registration to the study)
measure: Overall Survival
timeFrame: 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
measure: Progression Free Survival
timeFrame: 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
Other outcomes:
Locations:
city: Denver
country: United States
facility: CCOP - Colorado Cancer Research Program, Inc.
state: Colorado
city: Atlanta
country: United States
facility: Emory University Hospital - Atlanta
state: Georgia
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center, Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Veterans Affairs Medical Center - Lakeside Chicago
state: Illinois
city: Evanston
country: United States
facility: CCOP - Evanston
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Veterans Affairs Medical Center - Indianapolis (Roudebush)
state: Indiana
city: Cedar Rapids
country: United States
facility: CCOP - Cedar Rapids Oncology Project
state: Iowa
city: New Orleans
country: United States
facility: CCOP - Ochsner
state: Louisiana
city: Boston
country: United States
facility: New England Medical Center Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: CCOP - Ann Arbor Regional
state: Michigan
city: Kalamazoo
country: United States
facility: CCOP - Kalamazoo
state: Michigan
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Omaha
country: United States
facility: CCOP - Missouri Valley Cancer Consortium
state: Nebraska
city: Morristown
country: United States
facility: Morristown Memorial Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey
state: New Jersey
city: Perth Amboy
country: United States
facility: Raritan Bay Medical Center
state: New Jersey
city: Somerville
country: United States
facility: Somerset Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Albert Einstein Comprehensive Cancer Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Cancer Center
state: New York
city: Cleveland
country: United States
facility: Ireland Cancer Center
state: Ohio
city: Toledo
country: United States
facility: CCOP - Toledo Community Hospital Oncology Program
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania Cancer Center
state: Pennsylvania
city: Wynnewood
country: United States
facility: CCOP - MainLine Health
state: Pennsylvania
city: Nashville
country: United States
facility: Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Marshfield
country: United States
facility: CCOP - Marshfield Medical Research and Education Foundation
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Veterans Affairs Medical Center - Milwaukee (Zablocki)
state: Wisconsin
Study officials:
affiliation: Abramson Cancer Center at Penn Medicine
name: David I. Rosenthal, MD
role: STUDY_CHAIR
References:
citation: 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.