Oxaliplatin, Capecitabine, and Radiation Therapy in Patients Undergoing Surgery for Stage II, III, IV Esophageal Cancer

Esophageal Cancer Clinical Trial

Official title:

Phase II Study of Capecitabine in Combination With Oxaliplatin and Radiotherapy for Esophageal and Gastroesophageal Junction Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00470184
• Other study ID #: CDR0000543376
• Secondary ID: RPCI-I-64105
• Status: Completed
• Phase: Phase 2
• First received: May 3, 2007
• Last updated: September 19, 2013
• Start date: November 2006

Study information

• Verified date: September 2013
• Source: Roswell Park Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase II trial is studying how well giving oxaliplatin and capecitabine together with radiation therapy works in treating patients undergoing surgery for stage II, stage III, or stage IV esophageal cancer.

Description:

OBJECTIVES:

Primary

• Determine the complete pathologic response (complete response [CR]) rate in patients with stage II-IVA esophageal cancer treated with neoadjuvant oxaliplatin, capecitabine, and radiotherapy.

Secondary

• Determine the clinical efficacy and toxicity of this regimen in these patients.

• Determine the quality of life of patients treated with this regimen.

• Identify basal expression and changes in gene expression that relate to CR, relapse, and survival of patients treated with this regimen.

OUTLINE:

• Neoadjuvant chemoradiotherapy: Patients receive oxaliplatin IV over 2 hours on days 1, 15, and 29 (weeks 1, 3, and 5). Patients also undergo radiotherapy on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-38 and receive oral or enteral capecitabine twice daily on the same days they undergo radiotherapy.

• Surgery: At 4-6 weeks after completion of neoadjuvant chemoradiotherapy, patients who are eligible undergo esophagectomy.

• Adjuvant chemotherapy: Beginning 4-6 weeks after surgery, patients receive oxaliplatin IV over 2 hours on days 1, 15, and 29 and oral or enteral capecitabine twice daily on days 1-5, 8-12, 15-19, 22-26, and 29. Treatment repeats approximately every 14 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo tumor biopsies periodically. Collected samples are analyzed by gene expression studies, microarray analysis, and real-time quantitative reverse transcriptase-PCR to identify basal expression and changes in gene expression.

Quality of life is assessed periodically.

After completion of study treatment, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Diagnosis of squamous cell carcinoma of the esophagus or adenocarcinoma of the esophagus

• Stage II-IVA disease as determined by clinical staging, including endoscopy and CT scan with or without endoscopic ultrasound

• Bulk of gastroesophageal junction tumor should be in the esophagus

• Bronchoscopy with biopsy and cytology required if primary esophageal cancer is < 26 cm from incisors

• No known brain metastases

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1

• Life expectancy > 4 months

• WBC > 4,000/mm³

• ANC > 1,500/mm³

• Platelet count > 100,000/mm³

• Hemoglobin > 9 g/dL

• Bilirubin normal

• Creatinine normal

• AST < 2.5 times upper limit of normal (ULN)

• Alkaline phosphatase = 3 times ULN

• Able to take oral medication or undergo enteral administration of medication

• No peripheral neuropathy = grade 2

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 90 days after completion of study treatment

• No hypersensitivity to platinum compounds, fluoropyrimidines, or antiemetics administered in combination with protocol-directed chemotherapy

• No concurrent uncontrolled illness, including, but not limited to, any of the following:

• Ongoing or active infection

• Symptomatic congestive heart failure

• Unstable angina pectoris

• Cardiac arrhythmia

• Psychiatric illness or social situation that would preclude study compliance

• No history of second malignancy except for curatively treated carcinoma in situ of the cervix or nonmelanoma skin cancer

• Other cured tumors allowed at discretion of the principal investigator

• No known HIV or hepatitis B or C (active and/or previously treated)

PRIOR CONCURRENT THERAPY:

• No prior therapy for esophageal cancer

• No other concurrent investigational agents

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms

Intervention

Drug:
• capecitabine
Oral
• oxaliplatin
IV

Genetic:
• gene expression analysis
Correlative Study
• microarray analysis
Correlative Study
• reverse transcriptase-polymerase chain reaction
Correlative Study

Procedure:
• adjuvant therapy
Metastatic growth control
• biopsy
Examination of tissue type
• conventional surgery
Tissue removal
• neoadjuvant therapy
Tumor shrinkage
• quality-of-life assessment
Correlative Study

Radiation:
• radiation therapy
Undergoing radiation therapy

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York

Sponsors (2)

Lead Sponsor	Collaborator
Roswell Park Cancer Institute	National Comprehensive Cancer Network

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Response		5.5 weeks	No
Secondary	Overall Response Rate (Complete and Partial Response) as Measured by RECIST Criteria After Course 1		5.5 weeks	No
Secondary	Median Time to Progression		5.5 weeks	No
Secondary	Quality of Life Improved Rate		5.5 weeks	No