Overview

This trial is active, not recruiting.

Conditions adenocarcinoma of the esophagus, adenocarcinoma of the gastroesophageal junction, stage ii esophageal cancer
Treatments panitumumab, oxaliplatin, leucovorin calcium, fluorouracil, radiation therapy, therapeutic conventional surgery, laboratory biomarker analysis, high performance liquid chromatography, dna analysis, polymorphism analysis, pharmacological study, pharmacogenomic studies
Phase phase 2
Target EGFR
Sponsor University of Nebraska
Collaborator National Cancer Institute (NCI)
Start date February 2011
End date October 2015
Trial size 23 participants
Trial identifier NCT01307956, 221-09, NCI-2010-02056, P30CA036727

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

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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.
panitumumab ABX-EGF
Given IV
oxaliplatin 1-OHP
Given IV
leucovorin calcium CF
Given IV
fluorouracil 5-fluorouracil
Given IV
radiation therapy irradiation
Undergo radiation therapy
therapeutic conventional surgery
Undergo surgical resection
laboratory biomarker analysis
Correlative studies
high performance liquid chromatography HPLC
Correlative studies
dna analysis
Correlative studies
polymorphism analysis
Correlative studies
pharmacological study pharmacological studies
Correlative studies
pharmacogenomic studies Pharmacogenomic Study
Correlative studies

Primary Outcomes

Measure
Complete pathological response (pCR) rate
time frame: After 4 courses of protocol therapy

Secondary Outcomes

Measure
Proportion of patients who can undergo resection
time frame: Four weeks after completion of the chemo-radiation
Survival
time frame: From the first date of therapy until the date the patient dies
Time to treatment failure
time frame: From the first date of therapy until the date the patient is removed from study for any reason
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
Polymorphic variations in genomic DNA
time frame: At baseline (pre-treatment) and every 4 weeks only if initially elevated
Incidence of adverse events
time frame: When reported by patients, and at physical examinations every 2 weeks

Eligibility Criteria

Male or female participants at least 19 years old.

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

Additional Information

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
Principal investigator Jean Grem
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.
Trial information was received from ClinicalTrials.gov and was last updated in July 2011.
Information provided to ClinicalTrials.gov by University of Nebraska.
Location data was received from the National Cancer Institute and was last updated in October 2016.