Panitumumab, Combination Chemotherapy, and Radiation Therapy Before Surgery in Treating Patients With Advanced Esophageal or Gastroesophageal Junction Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2011 by University of Nebraska
Sponsor:
Collaborator:
Information provided by:
University of Nebraska
ClinicalTrials.gov Identifier:
NCT01307956
First received: March 1, 2011
Last updated: July 12, 2011
Last verified: July 2011
  Purpose

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


Condition Intervention Phase
Adenocarcinoma of the Esophagus
Adenocarcinoma of the Gastroesophageal Junction
Stage II Esophageal Cancer
Biological: panitumumab
Drug: oxaliplatin
Drug: leucovorin calcium
Drug: fluorouracil
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
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of Nebraska:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 23
Study Start Date: February 2011
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Biological: panitumumab
Given IV
Other Names:
  • ABX-EGF
  • MOAB ABX-EGF
  • monoclonal antibody ABX-EGF
  • Vectibix
Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Radiation: radiation therapy
Undergo radiation therapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Procedure: therapeutic conventional surgery
Undergo surgical resection
Other: laboratory biomarker analysis
Correlative studies
Other: high performance liquid chromatography
Correlative studies
Other Name: HPLC
Genetic: DNA analysis
Correlative studies
Genetic: polymorphism analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: pharmacogenomic studies
Correlative studies
Other Name: Pharmacogenomic Study

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.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01307956

Contacts
Contact: Mary "Beth" Kos, RN BSN OCN 402-559-4726 mekos@unmc.edu
Contact: Marsha Ketcham, RN OCN 402-559-5286 mketcham@unmc.edu

Locations
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    jgrem@unmc.edu   
Principal Investigator: Jean L. Grem         
Sponsors and Collaborators
University of Nebraska
Investigators
Principal Investigator: Jean Grem University of Nebraska
  More Information

No publications provided

Responsible Party: Grem, Jean, UNMC Eppley Cancer Center at the University of Nebraska Medical Center
ClinicalTrials.gov Identifier: NCT01307956     History of Changes
Other Study ID Numbers: 221-09, NCI-2010-02056, P30CA036727
Study First Received: March 1, 2011
Last Updated: July 12, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Antibodies
Antibodies, Monoclonal
Fluorouracil
Oxaliplatin
Leucovorin
Levoleucovorin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Vitamin B Complex
Vitamins

ClinicalTrials.gov processed this record on July 31, 2014