Trial of Panitumumab/Cisplatin/Fluorouracil Combined With Radiation in Esophageal Cancer

Study Overview
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Brief Summary
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The overall study objective is to evaluate the dose limiting toxicities and the recommended phase II dose of Panitumumab when combined with the standard of care treatment with cisplatin, fluorouracil and radiation in patients with locally advanced esophageal cancer. The investigators will also be assessing the ability of PET (Positron Emission Tomography) imaging to predict the degree of pathologic response. All patients will have a pre-study FDG (F-18 Fluorodeoxyglucose) PET scan and will receive radiation therapy and chemotherapy over a 35 day period. 4-8 weeks post radiation and chemotherapy patients will be restaged with a PET/CT scan. It is anticipated that approximately 30 patients enrolled will undergo an esophagectomy which is considered standard of care post radiation and chemotherapy. The surgery will allow us to compare this study regimen to the historical standard of care (Cisplatin/fluorouracil chemotherapy with radiation therapy).

Official Title
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A Phase I/II Study of Panitumumab/Cisplatin/Fluorouracil Combined With Radiation Preoperatively for Patients With Locally Advanced Esophageal Cancer

Conditions
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Cancer

Intervention / Treatment
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* Drug: Panitumumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Locally Advanced Esophageal cancer (stages T1N1 or T2-4 any N) Histology must be adenocarcinoma or squamous cell carcinoma Must be surgical candidate based on evaluation by a thoracic surgeon must have adequate organ function as defined by routine lab tests Exclusion Criteria: Insitu carcinoma prior chemotherapy for esophageal cancer Metastatic (stage IV disease) Tumors <5cm from the cricopharyngeus muscle, Tumors with >75% of tumor located within the stomach Active, uncontrolled cardiac disease subjects with >Grade 2 neuropathies. -

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Dose escalation study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Level -1<br>Panitumumab/Cisplatin/Fluorouracil and Radiation therapy 1.5mg/kg Panitumumab, 60mg/m2 cisplatin, 750mg/m2 5FU (Fluorouracil) | Drug: Panitumumab<br>* dose escalating 1.5mg/kg or 2.5mg/kg weekly during radiation. Cisplatin on Days 1 and 29, Fluorouracil on Days1-4 and Days 29-32.<br>|
| Experimental: Dose Level 1<br>Panitumumab/Cisplatin/Fluorouracil and Radiation therapy 1.5mg/kg Panitumumab, 80mg/m2 cisplatin, 1000mg/m2 5FU (Fluorouracil) | Drug: Panitumumab<br>* dose escalating 1.5mg/kg or 2.5mg/kg weekly during radiation. Cisplatin on Days 1 and 29, Fluorouracil on Days1-4 and Days 29-32.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MTD of Panitumumab in Combination With Cisplatin/Fluorouracil and Radiation for Locally Advanced Esophageal Cancer Determined by Number of Participants Experiencing DLT | Maximum Tolerated Dose (MTD) will be where 0 of 6 patients experienced Dose Limiting Toxicities (DLT) from start until 28 days after the completion of radiation. The investigator considered DLTs related to the treatment to be: grade 4 hematologic toxicity, grade 3 hematologic toxicity lasting >7 days, any neutropenic fever, all grade 3 non-hematologic toxicities (excluding alopecia and nausea/vomiting/diarrhea if controlled with antiemetics or anti-diarrheal agents), grade 4 lab abnormality (whether symptomatic or asymptomatic), any treatment related to death, any toxicity associated with 1) any single interruption of radiation >10 treatment days, 2) >2 interruptions of radiation per course, 3) a delay in completion of radiation by >14 days beyond planned treatment schedule, 4) inability to deliver >80% of planned treatment doses, 5) any infield grade 4 toxicity | approximately 18 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic Response | From therapy initiation through 30 days post surgery. 5.5 weeks of XRT/chemo, 4-8weeks post Radiation (XRT)/Chemo subjects to undergo a surgical resection, and study will be completed 4 weeks post surgery with surgical morbidity and mortality information | 20 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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esophageal cancer, Locally advanced esophageal cancer