Clinical trial NCT00470184: Oxaliplatin, Capecitabine, and Radiation Therapy in Patients Undergoing Surgery for Stage II, III, IV Esophageal Cancer
Official title: Phase II Study of Capecitabine in Combination With Oxaliplatin and Radiotherapy for Esophageal and Gastroesophageal Junction Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Esophageal Cancer
Keywords: adenocarcinoma of the esophagus
squamous cell carcinoma of the esophagus
stage II esophageal cancer
stage III esophageal cancer
stage IV esophageal cancer
Lead sponsor: Roswell Park Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Comprehensive Cancer Network
First posted: 2007-05-07
Enrollment: 41
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, 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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Complete Response
timeFrame: 5.5 weeks
Secondary outcomes:
measure: Overall Response Rate (Complete and Partial Response) as Measured by RECIST Criteria After Course 1
timeFrame: 5.5 weeks
measure: Median Time to Progression
timeFrame: 5.5 weeks
measure: Quality of Life Improved Rate
timeFrame: 5.5 weeks
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
Study officials:
affiliation: Roswell Park Cancer Institute
name: Nikhil Khushalani, MD
role: PRINCIPAL_INVESTIGATOR
References: