Panitumumab, Combination Chemotherapy, and Radiation Therapy Before Surgery in Treating Patients With Advanced Esophageal or Gastroesophageal Junction Cancer
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
Adenocarcinoma of the Esophagus
Adenocarcinoma of the Gastroesophageal Junction
Stage II Esophageal Cancer
Drug: leucovorin calcium
Radiation: radiation therapy
Procedure: therapeutic conventional surgery
Other: laboratory biomarker analysis
Other: high performance liquid chromatography
Genetic: DNA analysis
Genetic: polymorphism analysis
Other: pharmacological study
Other: pharmacogenomic studies
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Neo-Adjuvant Therapy With Oxaliplatin, Leucovorin, 5-Fluorouracil, Panitumumab (Vectibix) and Radiation in Patients With Locally Advanced Adenocarcinoma of the Esophagus or Gastroesophageal Junction|
- Complete pathological response (pCR) rate [ Time Frame: After 4 courses of protocol therapy ] [ Designated as safety issue: No ]Based on the proportion who achieve pCR. Evaluated using the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 guidelines.
- Proportion of patients who can undergo resection [ Time Frame: Four weeks after completion of the chemo-radiation ] [ Designated as safety issue: No ]
- Survival [ Time Frame: From the first date of therapy until the date the patient dies ] [ Designated as safety issue: No ]
- Time to treatment failure [ Time Frame: From the first date of therapy until the date the patient is removed from study for any reason ] [ Designated as safety issue: No ]
- Steady-state plasma concentrations of 5-FU [ Time Frame: Pre-treatment and at hours 22, 23, 43, and 44 hours during the 46-hr infusion week 1 ] [ Designated as safety issue: No ]
- Polymorphic variations in genomic DNA [ Time Frame: At baseline (pre-treatment) and every 4 weeks only if initially elevated ] [ Designated as safety issue: No ]
- Incidence of adverse events [ Time Frame: When reported by patients, and at physical examinations every 2 weeks ] [ Designated as safety issue: Yes ]
|Study Start Date:||February 2011|
|Estimated Primary Completion Date:||October 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (monoclonal antibody, chemotherapy, radiation)
Patients receive panitumumab 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.
Other Names:Drug: oxaliplatin
Other Names:Drug: leucovorin calcium
Other Names:Drug: fluorouracil
Other Names:Radiation: radiation therapy
Undergo radiation therapy
Other Names:Procedure: therapeutic conventional surgery
Undergo surgical resectionOther: laboratory biomarker analysis
Correlative studiesOther: high performance liquid chromatography
Other Name: HPLCGenetic: DNA analysis
Correlative studiesGenetic: polymorphism analysis
Correlative studiesOther: pharmacological study
Other Name: pharmacological studiesOther: pharmacogenomic studies
Other Name: Pharmacogenomic Study
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.
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01307956
|Contact: Mary "Beth" Kos, RN BSN OCNemail@example.com|
|Contact: Marsha Ketcham, RN OCNfirstname.lastname@example.org|
|United States, Nebraska|
|UNMC Eppley Cancer Center at the University of Nebraska Medical Center||Recruiting|
|Omaha, Nebraska, United States, 68198-6805|
|Contact: Jean L. Grem 402-559-6210 email@example.com|
|Principal Investigator: Jean L. Grem|
|Principal Investigator:||Jean Grem||University of Nebraska|