Oxaliplatin, Fluorouracil, Radiation Therapy, and Surgery in Treating Patients With Stage II or Stage III Cancer of the Esophagus or Gastroesophageal Junction - Full Text View

Sponsors and Collaborators:	Southwest Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00086996

Purpose

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin and fluorouracil, work in 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. Oxaliplatin and fluorouracil may make tumor cells more sensitive to radiation therapy and may kill more tumor cells. Giving chemotherapy and radiation therapy before surgery may shrink the tumor so that it can be removed.

PURPOSE: This phase II trial is studying how well giving oxaliplatin together with fluorouracil and radiation therapy works in treating patients who are undergoing surgery for stage II or stage III cancer of the esophagus or gastroesophageal junction.

Condition	Intervention	Phase
Esophageal Cancer	Drug: fluorouracil Drug: oxaliplatin Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy Procedure: radiation therapy	Phase II

MedlinePlus related topics: Cancer Esophageal Cancer Esophagus Disorders

Drug Information available for: Fluorouracil Oxaliplatin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Oxaliplatin (NSC-266046) Plus Protracted Infusion 5-Fluorouracil And Radiation For Potentially Curable Esophageal Cancer: A Phase II Trial With Molecular Correlates

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Pathological complete response [ Designated as safety issue: No ]

Estimated Enrollment:	85
Study Start Date:	September 2004
Estimated Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the pathologic complete response probability in patients with stage II or III adenocarcinoma of the esophagus or gastroesophageal junction treated with neoadjuvant oxaliplatin, fluorouracil, and radiotherapy followed by definitive surgical resection.

Secondary

Determine the frequency and severity of toxic effects associated with this neoadjuvant regimen in these patients.
Determine the overall survival and progression-free survival of patients treated with this regimen.
Correlate, preliminarily, initial mRNA levels of the genes for thymidylate synthase (TS), γ-glutamyl transpeptidase (γGT), γ-glutamyl cysteine (γ-GCS), DNA excision repair cross-complementing (ERCC-1), and xeroderma pigmentosum (XPA) with response and survival of patients treated with this regimen.
Correlate, preliminarily, the mRNA levels of TS, γGT, γ-GCS, ERCC-1, and XPA before and after treatment with this regimen with survival of these patients.
Correlate, preliminarily, specific genetic polymorphisms of TS and ERCC-1 with tumor response and overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Neoadjuvant chemoradiotherapy: Patients receive oxaliplatin IV over 2 hours on days 1, 15, and 29 and fluorouracil (5-FU) IV continuously on days 8-43. Beginning on day 8, patients also undergo radiotherapy once daily, 5 days a week, for 5 weeks.
Surgery: Patients with stable disease or better undergo surgical resection 4-10 weeks after completion of chemoradiotherapy.
Adjuvant chemotherapy: Beginning 4-10 weeks after surgery, patients receive chemotherapy comprising oxaliplatin IV over 2 hours on days 1, 15, and 29 and 5-FU IV continuously on days 1-36.

Treatment continues in the absence of unacceptable toxicity or disease progression.

Patients are followed every 3 months for 1 year and then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 45-85 patients will be accrued for this study within 17-21 months.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed primary adenocarcinoma of the thoracic esophagus or gastroesophageal junction
- No recurrent disease
- Primary esophageal tumor at least 20 cm below the incisors (if < 26 cm below the incisors, a bronchoscopy must be performed and cytology must be negative)
- Esophageal disease confined to esophagus and peri-esophageal soft tissue
- Gastroesophageal junction disease extending ≤ 2 cm into the gastric cardia
Clinical stage II or III disease by CT scan or MRI
- If no esophageal mass is detected by these methods, esophageal endoscopic ultrasound is required to determine stage
- Positron-emission tomography scan is required to confirm stage
Measurable or non-measurable disease by x-ray, scanning, or physical examination
No celiac axis nodes ≥ 1.5 cm
- Measurable regional lymph nodes ≥ 1.5 cm at stations 2-10=N1 OR subdiaphragmatic lymph nodes at stations 15-19 ≤ 1.5 cm by CT scan or MRI allowed
- Palpable supraclavicular lymph nodes must be free of metastatic esophageal cancer by biopsy

PATIENT CHARACTERISTICS:

Age

Over 18

Performance status

Zubrod 0-2

Life expectancy

Not specified

Hematopoietic

Absolute neutrophil count ≥ 1,500/mm^3
WBC ≥ 3,000/mm^3
Hemoglobin ≥ 10.0 g/dL (transfusion allowed)

Hepatic

Albumin ≥ 3 g/dL
Bilirubin normal

Renal

Creatinine ≤ 1.5 times upper limit of normal

Cardiovascular

No myocardial infarction or cerebrovascular event within the past 6 months

Pulmonary

No active pneumonia or inflammatory lung infiltrate

Other

No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
No peripheral neuropathy ≥ grade 2
Not pregnant or nursing
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

No prior chemotherapy for esophageal cancer

Endocrine therapy

Not specified

Radiotherapy

No prior radiotherapy for esophageal cancer
No concurrent intensity-modulated radiotherapy

Surgery

No prior surgical resection or attempted surgical resection of esophageal cancer

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00086996

Show 143 Study Locations

Sponsors and Collaborators

Southwest Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Lawrence P. Leichman, MD	Desert Regional Medical Center Comprehensive Cancer Center
Investigator:	Charles R. Thomas, MD	Oregon Health and Science University Cancer Institute

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000371963, SWOG-S0356
Study First Received:	July 8, 2004
Last Updated:	October 23, 2008
ClinicalTrials.gov Identifier:	NCT00086996
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

adenocarcinoma of the esophagus
stage II esophageal cancer
stage III esophageal cancer

Study placed in the following topic categories:

Oxaliplatin
Digestive System Neoplasms
Digestive System Diseases
Esophageal disorder
Gastrointestinal Diseases
Fluorouracil

Head and Neck Neoplasms
Esophageal Neoplasms
Gastrointestinal Neoplasms
Esophageal Diseases
Adenocarcinoma
Esophageal neoplasm

Additional relevant MeSH terms:

Antimetabolites
Neoplasms
Antimetabolites, Antineoplastic
Neoplasms by Site
Immunologic Factors
Molecular Mechanisms of Pharmacological Action

Antineoplastic Agents
Therapeutic Uses
Physiological Effects of Drugs
Immunosuppressive Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009