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

Roswell Park Comprehensive Cancer Center

Status and phase

Completed

Phase 2

Conditions

Esophageal Cancer

Treatments

Radiation: radiation therapy

Procedure: biopsy

Procedure: neoadjuvant therapy

Genetic: microarray analysis

Drug: oxaliplatin

Drug: capecitabine

Procedure: conventional surgery

Genetic: reverse transcriptase-polymerase chain reaction

Procedure: quality-of-life assessment

Procedure: adjuvant therapy

Genetic: gene expression analysis

Study type

Interventional

Funder types

Other

NETWORK

Identifiers

NCT00470184

RPCI-I-64105 (Other Identifier)

CDR0000543376

Details and patient eligibility

About

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.

Full 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.

Enrollment

41 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

41 participants in 1 patient group

Chemo

Experimental group

Description:

Oxaliplatin 85 mg/m2 will be administered IV on days 1, 15 and 29. Capecitabine 1250 mg/m2 will be administered in 2 divided daily doses P0 or via enteral tube, on radiation days only (Monday- Friday/ weekly). Capecitabine will be continued until the final dose of radiotherapy

Treatment: