Perioperative Panitumumab and Epirubicin, Oxaliplatin and Xeloda (EOX) in Patients With Gastroesophageal Adenocarcinoma

Study Overview
=================
Brief Summary
-----------------
A pilot study to determine the safety of using perioperative panitumumab with EOX (epirubicin, oxaliplatin, and capecitabine) in patients with adenocarcinoma of the esophagus and stomach.

Official Title
-----------------
A Pilot Study of Perioperative Panitumumab in Combination With Epirubicin, Oxaliplatin and Xeloda in Patients With Resectable Gastroesophageal Adenocarcinoma

Conditions
-----------------
Esophageal Adenocarcinoma, Gastric Adenocarcinoma

Intervention / Treatment
-----------------
* Drug: panitumumab, epirubicin, oxaliplatin, xeloda


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must have histologically or cytologically confirmed diagnosis of adenocarcinoma of the stomach, gastroesophageal junction, or lower third of the esophagus, AJCC stage II-IIIB (gastric) or IIA-IVA (esophageal). M1a disease will be included, but not T4 lesions. No prior radiation or chemotherapy including anti-EGFR or vascular endothelial growth factor (VEGF) antibody or tyrosine kinase inhibitor treatments. All patients must have staging endoscopic ultrasound (EUS) prior to enrollment. Men or Women >18 years of Age ECOG performance status <2 (Karnofsky >60%, see Appendix A). Cardiac ejection fraction >45% by echocardiogram or MUGA scan. Must be able to either swallow pills or have gastrostomy tube in place for administration of enteral medications. Patients must have normal organ, metabolic and marrow function as defined below: Hematologic function, as follows: Absolute neutrophil count (ANC) ≥ 1.5 x 109/L Platelet count ≥ 100 x 109/L Hemoglobin ≥ 9.0 g/dL Renal function, as follows: Creatinine < or = 1.5 mg/dL x ULN Hepatic function, as follows: Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT)< or = 3 x ULN Total bilirubin < 1.5 x ULN Metabolic function, as follows: Magnesium ≥ lower limit of normal Calcium < or = lower limit of normal -Human IgG is known to cross the placental barrier; therefore, Panitumumab may be transmitted from the mother to the developing fetus. In women of childbearing potential, appropriate contraceptive measures must be used during treatment with panitumumab and for 6 months following the last dose of panitumumab. If panitumumab is used during pregnancy or if the patient becomes pregnant while receiving this drug, she should be apprised of the potential risk for loss of the pregnancy or potential hazard to the fetus. 3.1.10 Ability to understand and the willingness to sign and date a written IEC/IRB approved informed consent form. Exclusion Criteria: Evidence of distant metastatic disease. T4 tumor on initial staging studies. History of another primary cancer, except: Curatively treated in situ cervical cancer Curatively resected non-melanoma skin cancer Other primary solid tumor curatively treated with no known active disease present and no treatment administered for ³ 5 years prior to enrollment Relative or absolute contraindications to surgery which in the opinion of the investigator make the patient a poor candidate for surgical resection. History of allergic reactions attributed to compounds of similar chemical or biologic composition to panitumumab or other agents used in study. Subjects requiring chronic use of immunosuppressive agents (e.g., methotrexate, cyclosporine). 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 the study participation or investigational product(s) administration or may interfere with the interpretation of the results. Subject unwilling or unable to comply with study requirements. Women who test positive for serum or urine pregnancy test < 72 hours before randomization or are breast feeding. Known positive test(s) for human immunodeficiency virus infection, hepatitis C virus, acute or chronic active hepatitis B infection. Major surgery with 28 days or minor surgery within 14 days of study enrollment. Men or women of child-bearing potential (women who are post-menopausal < 52 weeks, not surgically sterilized, or not abstinent) not consenting to use adequate contraception (per institutional standard of care) during the course of the study and after the last investigational product(s) administration (24 weeks for women, 4 weeks for men). Subjects with > grade 1 neuropathy at baseline. Contraindication to port-a-cath placement.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EOXP chemotherapy<br>open-label, single-arm EOXP Epirubicin 50mg/m2 by IV on day 1 of each 21 day cycle, Oxaliplatin 100 mg/m2 by IV on day 1 of each 21 day cycle, Capecitabine 400 mg/m2 twice daily by mouth on days 1-21 of the 21 day cycle Panitumumab - 9mg/kg by IV on day 1 of each 21 day cycle | Drug: panitumumab, epirubicin, oxaliplatin, xeloda<br>* pilot study<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability | Safety and tolerability were measured by assessing the number of participants able to complete 3 cycles of pre-operative chemotherapy | after 3 cycles of pre-operative chemotherapy (approx 21 days per cycle) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| R0 Resection Rate | percentage of participants who have microscopically negative margins (no tumor at/near the edge of what is resected) at the time of surgical resection | time of surgery = after 3 cycles (approx 63 days) of pre-operative EOX-P chemotherapy | 
| Progression-Free Survival | measured from the first day of treatment to the day when conclusive evidence of new disease is found | up to 72 months | 
| Pathologic Complete Response Rate | For patients who undergo complete resection, those who have no evidence of residual viable tumor in the surgical specimen will be declared to have achieved a complete pathologic response (pCR), and the overall percentage of patients with pCR will be determined. | at surgical resection, after 3 cycles pre-operative chemotherapy (approx 63 days) | 
| Overall Survival | Overall survival (OS) is the duration from start of treatment to time of death from any cause. | duration from enrollment to death (up to 6 years) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
gastric, esophageal, panitumumab