Panitumumab, Paclitaxel, Carboplatin and 5FU in the Treatment of Potentially Resectable Gastroesophageal Adenocarcinoma

Study Overview
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Brief Summary
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This is an open-label, Phase II, single-stage study evaluating the use of panitumumab, paclitaxel, carboplatin and 5FU as an induction regimen in subjects with gastroesophageal adenocarcinoma. The expectation is that this combination will both increase potential overall survival by incorporating novel biologic therapy in the neoadjuvant setting and decrease potential surgical mortality by eliminating pre-operative radiation therapy.

Official Title
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A Phase II Study of Pre-operative Panitumumab, Paclitaxel, Carboplatin and Continuous Infusion 5FU in the Treatment of Potentially Resectable Gastroesophageal Adenocarcinoma

Conditions
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Gastroesophageal Adenocarcinoma, Adenocarcinoma of the Distal Esophagus, Adenocarcinomas of the Gastroesophageal Junction, Adenocarcinoma of the Proximal Stomach

Intervention / Treatment
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* Drug: Panitumumab
* Drug: Paclitaxel
* Drug: Carboplatin
* Drug: 5FU


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy-proven adenocarcinoma of the distal esophagus, gastroesophageal junction, or proximal stomach (within 5cm of gastroesophageal junction) No prior treatment for this disease AJCC (American Joint Committee on Cancer) clinical stage II to IVA, potentially resectable disease Measurable disease per RECIST 1.0 criteria Medically fit for surgery; surgical consultation is encouraged prior to initiation of treatment ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1 Male or female; aged equal to or greater than 18 years Life expectancy of greater than 3 months Good organ, metabolic, bone marrow, and pulmonary function as specified in the protocol Functioning central venous access device prior to treatment initiation Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for at least 6 months following the last administration of panitumumab Ability to understand and the willingness to sign a written IRB (Institutional Review Board) approved informed consent Exclusion Criteria: Prior treatment for this disease History of another primary cancer except curatively treated in situ cervical cancer, curatively resected nonmelanoma skin cancer, or other primary solid tumor curatively treated with no active disease present and no treatment administered for at least 5 years prior to enrollment History or known presence of central nervous system metastases History of allergic reactions attributed to compounds similar chemical or biologic composition to panitumumab, paclitaxel, carboplatin, or 5FU Prior anti-EGFr-antibody therapy or treatment with small molecule EGFr inhibitors Systemic chemotherapy, hormonal therapy, immunotherapy, or experimental or approved proteins/antibodies within 30 days prior to enrollment Chronic use of immunosuppressive agents with the exception of corticosteroids Any investigational agent or therapy within 30 days prior to enrollment Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements History of interstitial lung disease, e.g., pneumonitis or pulmonary fibrosis or any evidence of interstitial lung disease on baseline chest CT scan History of any medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risks associated with study participation or investigational product(s) administration or may interfere with the interpretation of the results Unwilling or unable to comply with study requirements Female who tests positive for serum or urine pregnancy test or is breast feeding Known positive test(s) for human immunodeficiency virus infection, hepatitis C virus, acute or chronic active hepatitis B infection Major surgery within 28 days or minor surgery within 7 days prior to treatment. Placement of a central venous access device less than one day prior to treatment start Male or female of childbearing potential (women who are post-menopausal less than 52 weeks, not surgically sterilized, or not abstinent) not consenting to use adequate contraception prior to study entry and for at least 6 months following the last administration of panitumumab Arterial ischemic event (myocardial infarction, stroke) within 3 months prior to enrollment Ongoing therapeutic anticoagulation

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group<br>Panitumumab 9mg/kg on Days 1, 22, and 43 Paclitaxel 200mg/m2 on Days 1 and 22 Carboplatin AUC=6 on Days 1 and 22 5FU 225mg/m2/day on Days 1-15 and 22-36 | Drug: Panitumumab<br>* Panitumumab 9mg/kg on Days 1, 22, and 43<br>* Other names: Vectibix;Drug: Paclitaxel<br>* Paclitaxel 200mg/m2 on Days 1 and 22<br>* Other names: Taxol;Drug: Carboplatin<br>* Carboplatin AUC=6 on Days 1 and 22<br>* Other names: Paraplatin, CBDCA;Drug: 5FU<br>* 5FU 225mg/m2/day on Days 1-15 and 22-36<br>* Other names: 5-fluorouracil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | The primary endpoint is overall response rate (ORR) as determined per RECIST guidelines version 1.1 from baseline and restaging scans conducted between Days 36 to 43. Response is defined as the occurrence of either Complete Response (CR) or Partial Response (PR) as best response. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm. A PR is defined as at least a 30% decrease in the sum of diameters of the target lesions taking as reference the baseline sum diameters. | From the start of study treatment until restaging evaluation performed between days 36 to 43 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic Response Rate | The patient will be scored as having had a pathologic complete response (pCR) if the routine histologic examination of the resected specimen shows no residual invasive cancer by standard hematoxylin and eosin (H&E) examination. | At time of surgery (between days 50 to 64) | 
| Resection Rate of Surgery | The patient will be scored as having an R0 resection, if no invasive cancer is detected involving the margins of the resection by routine microscopic hematoxylin and eosin (H&E)examination, and the operative report indicates complete resection with no residual disease. The patient will be scored as having an R1 resection, if invasive cancer is detected involving the margins of resection by routine microscopic hematoxylin and eosin (H&E) examination, and the operative report indicates complete resection with no residual disease. The patient will be scored as having an R2 resection, if the operative report indicates incomplete resection or gross residual disease. | At time of surgery (between days 50 to 64) | 
| Thirty-day Surgical Mortality | All subjects who have undergone surgical resection will be followed for a 30-day postoperative safety evaluation. Death from any cause within 30 days of the date of surgery will be considered a surgical mortality death. | From date of surgery to 30 days after date of surgery | 
| Survival |  | 2-year survival from first dose of panitumumab |