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

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ClinicalTrials.gov Identifier: NCT01307956
Recruitment Status : Terminated (Drug manufacturer - Amgen requested, per DSMB observation in POWER trial.)
First Posted : March 3, 2011
Results First Posted : March 13, 2018
Last Update Posted : March 13, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Jean Grem, MD, University of Nebraska

Brief Summary:
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. Monoclonal antibodies, such as panitumumab, may interfere with the ability of tumor cells to grow and spread. 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, by stopping them from dividing, or by stopping them from spreading. 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.

Condition or disease Intervention/treatment Phase
Adenocarcinoma of the Gastroesophageal Junction Esophageal Adenocarcinoma Stage IIA Esophageal Cancer Stage IIB Esophageal Cancer Drug: Fluorouracil Other: Laboratory Biomarker Analysis Drug: Leucovorin Calcium Drug: Oxaliplatin Biological: Panitumumab Other: Pharmacological Study Radiation: Radiation Therapy Procedure: Therapeutic Conventional Surgery Phase 2

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 radiation therapy. Patients with residual disease receive 4 additional courses of FOLFOX chemotherapy on days 1, 15, 29, and 42.

After completion of study treatment, patients are followed up every 3 months for 2 years and then annually thereafter.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : February 2011
Actual Primary Completion Date : June 2015
Actual Study Completion Date : June 2015

Resource links provided by the National Library of Medicine

Drug Information available for: Panitumumab
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Treatment (panitumumab, 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 radiation therapy. Patients with residual disease receive 4 additional courses of FOLFOX chemotherapy on days 1, 15, 29, and 42.
Drug: Fluorouracil
Given IV
Other Names:
  • 5-Fluoro-2,4(1H, 3H)-pyrimidinedione
  • 5-Fluorouracil
  • 5-Fluracil
  • 5-FU
  • AccuSite
  • Carac
  • Fluoro Uracil
  • Fluouracil
  • Flurablastin
  • Fluracedyl
  • Fluracil
  • Fluril
  • Fluroblastin
  • Ribofluor
  • Ro 2-9757
  • Ro-2-9757
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Leucovorin Calcium
Given IV
Other Names:
  • Adinepar
  • Calcifolin
  • Calcium (6S)-Folinate
  • Calcium Folinate
  • Calcium Leucovorin
  • Calfolex
  • Calinat
  • Cehafolin
  • Citofolin
  • Citrec
  • Citrovorum Factor
  • Cromatonbic Folinico
  • Dalisol
  • Disintox
  • Divical
  • Ecofol
  • Emovis
  • Factor, Citrovorum
  • Flynoken A
  • Folaren
  • Folaxin
  • FOLI-cell
  • Foliben
  • Folidan
  • Folidar
  • Folinac
  • Folinate Calcium
  • folinic acid
  • Folinic Acid Calcium Salt Pentahydrate
  • Folinoral
  • Folinvit
  • Foliplus
  • Folix
  • Imo
  • Lederfolat
  • Lederfolin
  • Leucosar
  • leucovorin
  • Rescufolin
  • Rescuvolin
  • Tonofolin
  • Wellcovorin
Drug: Oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Ai Heng
  • Aiheng
  • Dacotin
  • Dacplat
  • Diaminocyclohexane Oxalatoplatinum
  • Eloxatin
  • Eloxatine
  • JM-83
  • Oxalatoplatin
  • Oxalatoplatinum
  • RP 54780
  • RP-54780
  • SR-96669
Biological: Panitumumab
Given IV
Other Names:
  • ABX-EGF
  • ABX-EGF Monoclonal Antibody
  • ABX-EGF, Clone E7.6.3
  • MoAb ABX-EGF
  • Monoclonal Antibody ABX-EGF
  • Vectibix
Other: Pharmacological Study
Correlative studies
Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • Irradiation
  • RADIATION
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation
Procedure: Therapeutic Conventional Surgery
Undergo surgical resection



Primary Outcome Measures :
  1. Complete Pathological Response (pCR) Rate [ Time Frame: Up to 8 weeks ]
    Based on the proportion who achieve pCR based on the first 4 courses of protocol treatment. Evaluated using the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 guidelines. Means (with associated standard errors), medians (with ranges), percentages and 95% confidence intervals will be reported as appropriate.


Secondary Outcome Measures :
  1. Proportion of Patients Who Can Undergo Resection [ Time Frame: 4 weeks after completion of the radiation ]
    Restaging with repeat imaging studies will be performed. If no contraindication for surgical resection is identified, resection will be performed. Means (with associated standard errors), medians (with ranges), percentages and 95% confidence intervals will be reported as appropriate.


Other Outcome Measures:
  1. Incidence of Adverse Events Graded Using the National Cancer Institute Common Toxicity Criteria Version 3.0 [ Time Frame: Up to 5 years ]
  2. Polymorphic Variations in Genomic Deoxyribonucleic Acid (DNA) (Including Thymidylate Synthase, Excision Repair Cross-complementing Rodent Repair Deficiency, Complementation Group 2 [ERCC2]/SPD, RAD51 and Breast Cancer [BRCA]2) [ Time Frame: Pre-treatment, and at hours 22, 23, 43, and 44 hours during the 46-hr infusion week 1 ]
  3. Progression-free Survival [ Time Frame: Up to 5 years ]
    Descriptively summarized using the method of Kaplan-Meier.

  4. Steady-state Plasma Concentrations of Fluorouracil [ Time Frame: Pre-treatment, and at hours 22, 23, 43, and 44 hours during the 46-hr infusion week 1 ]
    Descriptive statistics (means, proportions and 95% confidence intervals) will be used to examine the association of 5-FU and polymorphic variations in genomic DNA with clinical toxicity and response.

  5. Survival [ Time Frame: From the first date of therapy until the date the patient dies, assessed up to 5 years ]
    Descriptively summarized using the method of Kaplan-Meier.

  6. Time to Treatment Failure [ Time Frame: From the first date of therapy until the date the patient is removed from study for any reason, assessed up to 5 years ]


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Ages Eligible for Study:   19 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01307956


Locations
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
Sponsors and Collaborators
University of Nebraska
National Cancer Institute (NCI)
Investigators
Principal Investigator: Jean Grem University of Nebraska

Responsible Party: Jean Grem, MD, Principal Investigator, University of Nebraska
ClinicalTrials.gov Identifier: NCT01307956     History of Changes
Other Study ID Numbers: 221-09
NCI-2010-02056 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
221-09 ( Other Identifier: University of Nebraska Medical Center )
P30CA036727 ( U.S. NIH Grant/Contract )
First Posted: March 3, 2011    Key Record Dates
Results First Posted: March 13, 2018
Last Update Posted: March 13, 2018
Last Verified: February 2018

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
Immunoglobulins
Fluorouracil
Antibodies, Monoclonal
Calcium, Dietary
Oxaliplatin
Leucovorin
Levoleucovorin
Folic Acid
Immunologic Factors
Physiological Effects of Drugs
Bone Density Conservation Agents
Antineoplastic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents