Clinical trial NCT01307956: Panitumumab, Combination Chemotherapy, & Radiation Therapy in Esophageal or Gastroesophageal Junction Cancer
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Adenocarcinoma of the Gastroesophageal Junction
Esophageal Adenocarcinoma
Stage IIA Esophageal Cancer
Stage IIB Esophageal Cancer
Lead sponsor: University of Nebraska
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2011-03-03
Enrollment: 11
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Complete Pathological Response (pCR) Rate
timeFrame: Up to 8 weeks
Secondary outcomes:
measure: Number of Patients Who Can Undergo Resection
timeFrame: 4 weeks after completion of the radiation
Other outcomes:
measure: Progression-free Survival
timeFrame: Patients were followed from time of consent until the date of first documented progession or date of death from any cause, whichever came first, assessed up to 100 months.
measure: Overall Survival
timeFrame: From the first date of therapy until the date the patient dies, assessed up to 100 months
Locations:
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
Study officials:
affiliation: University of Nebraska
name: Jean L Grem, MD
role: PRINCIPAL_INVESTIGATOR
References: