Panitumumab, Combination Chemotherapy, and Radiation Therapy Before Surgery in Treating Patients With Advanced Esophageal or Gastroesophageal Junction Cancer
Conditions
Adenocarcinoma of the Esophagus - Adenocarcinoma of the Gastroesophageal Junction - Stage II Esophageal Cancer
Conditions: official terms
Adenocarcinoma - Esophageal Neoplasms
Study Type
Interventional
Study Phase
Phase 2
Study Design
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: panitumumab Type: Biological
Name: oxaliplatin Type: Drug
Name: leucovorin calcium Type: Drug
Name: fluorouracil Type: Drug
Name: radiation therapy Type: Radiation
Name: therapeutic conventional surgery Type: Procedure
Name: laboratory biomarker analysis Type: Other
Name: high performance liquid chromatography Type: Other
Name: DNA analysis Type: Genetic
Name: polymorphism analysis Type: Genetic
Name: pharmacological study Type: Other
Name: pharmacogenomic studies Type: Other
Overall Status
Recruiting
Summary
RATIONALE: Monoclonal antibodies, such as panitumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as oxaliplatin, leucovorin calcium, and fluorouracil, 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 monoclonal antibody therapy together with chemotherapy and 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 panitumumab, combination chemotherapy, and radiation therapy together before surgery works in treating patients with advanced esophageal or gastroesophageal (GE) junction cancer
Detailed Description
PRIMARY OBJECTIVES:

I. To determine the pathologic complete response rate of a modified FOLFOX-6 regimen (leucovorin calcium, fluorouracil, and oxaliplatin) given with panitumumab at two-week intervals x 4 cycles in combination with external beam radiation therapy for patients with locally advanced adenocarcinoma of the esophagus.

SECONDARY OBJECTIVES:

I. To determine the toxicities and ability to complete the planned treatment. II. To determine the achieved steady-state plasma concentrations of 5-FU (fluorouracil) and correlate these with clinical toxicity.

III. To assess the potential importance of polymorphic variations in genomic deoxyribonucleic acid (DNA) of pertinent genes whose protein products are the targets of the anti-neoplastic drugs used in the clinical protocol on response and toxicity to therapy.

OUTLINE:

Patients receive panitumumab intravenously (IV) over 1 hour on day 1. Patients also receive oxaliplatin IV and leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46 hours on day 1 (FOLFOX chemotherapy). Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Within 24 hours of the start of chemotherapy, patients undergo radiation therapy 5 days a week for 5.5 weeks. Patients then undergo surgery within 6-8 weeks after completion of chemotherapy and radiation therapy. Patients with residual disease receive 4 additional courses of FOLFOX chemotherapy.

After completion of study treatment, patients are followed up every 3 months.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 19 Years
Gender: Both
Criteria: Inclusion Criteria:

- Patients must have resectable adenocarcinoma of the esophagus or GE-junction and are medically fit to undergo surgery; patients must have no evidence of distant metastasis based on imaging studies

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

- Absolute neutrophil count (ANC) of at least 2000 per mcL

- Platelet count of at least 100,000 per mcL

- Serum creatinine less than or equal to 2.0 mg/dL

- Serum magnesium greater than or equal to 1.8 mg/dL

- Total bilirubin less than or equal to 2.0 mg per dL

- Measurable disease is not required for this study, since the primary endpoint is complete pathologic response

- The patient must be aware of the neoplastic nature of his/her disease and willingly provide written, informed consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts

Exclusion Criteria:

- Prior therapy: patients with prior history of mediastinal radiation exposure will be ineligible; patients may not have received prior chemotherapy, or antibody therapy for esophageal or GE-Junction adenocarcinoma

- History of allergy to platinum compounds or to antiemetics appropriate for administration in conjunction with protocol-directed chemotherapy

- Patients with a prior history of marked intolerance to 5-fluoropyrimidines (5-FU, floxuridine, capecitabine, 5-fluorocytosine [flucytosine]), since such patients may have deficiency of dihydropyrimidine dehydrogenase, which places them at risk for severe and life-threatening toxicity with 5-FU

- Uncontrolled inter-current illness including, but not limited to ongoing or active infection requiring intravenous antibiotics, ongoing immunosuppressive therapy (except for replacement steroids), active human immunodeficiency virus (HIV) infection, that might jeopardize the ability of the patient to receive the chemotherapy program outlined in this protocol with reasonable safety

- Clinically significant cardiac disease (including symptomatic congestive heart failure, myocardial infarction, unstable angina pectoris, or serious, uncontrolled cardiac arrhythmia) within 1 year of study enrollment

- Pregnant and nursing women, or women planning to become pregnant within 6 months after the end of treatment, are excluded from this study; a negative pregnancy test will be required of women of child-bearing age within 72 hours of study enrollment; subjects (male or female) who are not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment are excluded

- History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest computed tomography (CT) scan, since the risk of radiation-associated pneumonitis would be increased in such individuals

- Patients with prior malignancy will be excluded except for adequately treated basal cell or squamous cell skin cancer, adequately treated noninvasive carcinomas, or other cancers from which the patient has been disease-free for at least 5 years

- Patients receiving an investigational agent within 30 days before enrollment
Location
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
Omaha, Nebraska, United States
Status: Recruiting
Contact: Jean L. Grem - 402-559-6210 - jgrem@unmc.edu
Start Date
February 2011
Sponsors
University of Nebraska
Source
University of Nebraska
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page