Panitumumab, Combination Chemotherapy, & Radiation Therapy in Esophageal or Gastroesophageal Junction Cancer

NCT ID: NCT01307956

Last Updated: 2023-10-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-02-28
• Study Completion Date: 2015-12-23

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.

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.

Conditions

Adenocarcinoma of the Gastroesophageal Junction; Esophageal Adenocarcinoma; Stage IIA Esophageal Cancer; Stage IIB Esophageal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Fluorouracil

Intervention Type: DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Leucovorin Calcium

Intervention Type: DRUG

Given IV

Oxaliplatin

Intervention Type: DRUG

Given IV

Panitumumab

Intervention Type: BIOLOGICAL

Given IV

Pharmacological Study

Intervention Type: OTHER

Correlative studies

Radiation Therapy

Intervention Type: RADIATION

Undergo radiation therapy

Therapeutic Conventional Surgery

Intervention Type: PROCEDURE

Undergo surgical resection

Interventions

Fluorouracil

Given IV

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Leucovorin Calcium

Given IV

Intervention Type: DRUG

Oxaliplatin

Given IV

Intervention Type: DRUG

Panitumumab

Given IV

Intervention Type: BIOLOGICAL

Pharmacological Study

Correlative studies

Intervention Type: OTHER

Radiation Therapy

Undergo radiation therapy

Intervention Type: RADIATION

Therapeutic Conventional Surgery

Undergo surgical resection

Intervention Type: PROCEDURE

Other Intervention 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; 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; 1-OHP; Ai Heng; Aiheng; Dacotin; Dacplat; Diaminocyclohexane Oxalatoplatinum; Eloxatin; Eloxatine; JM-83; Oxalatoplatin; Oxalatoplatinum; RP 54780; RP-54780; SR-96669; ABX-EGF; ABX-EGF Monoclonal Antibody; ABX-EGF, Clone E7.6.3; MoAb ABX-EGF; Monoclonal Antibody ABX-EGF; Vectibix; Cancer Radiotherapy; Irradiate; Irradiated; Irradiation; RADIATION; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation

Eligibility 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

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Nebraska

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean L Grem, MD

Role: PRINCIPAL_INVESTIGATOR

University of Nebraska

Locations

University of Nebraska Medical Center

Omaha, Nebraska, United States

Countries

United States

Other Identifiers

NCI-2010-02056

Identifier Type: REGISTRY

Identifier Source: secondary_id

P30CA036727

Identifier Type: NIH

Identifier Source: secondary_id

View Link

0221-09-FB

Identifier Type: -

Identifier Source: org_study_id