Phase II Study of Irinotecan and Panitumumab
Condition: Esophageal Cancer
Intervention: Panitumumab; Irinotecan
Intervention description: 9mg/kg IV Day 1 Cycle = 21 days; 125mg/m2 IV Day 1 and Day 8
Intervention MeSH terms: Irinotecan; Panitumumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Panitumumab; Irinotecan; Esophageal Adenocarcinoma; Phase II

Summary:

      This study proposes a single-arm, phase II study of irinotecan with panitumumab as
      second-line therapy for patients with advanced esophageal adenocarcinoma. Efficacy will be
      assessed by response rate, with an exploratory outcome endpoint of time to progression (as
      panitumumab may result in prolonged stable disease). In addition to the usual safety
      assessments, molecular correlates will be carried out in order to search for pharmacodynamic
      and pharmacogenomic features that may correlate with response. Measures of host/patient
      immune function will be assessed by evaluating the relationship between Fc receptor
      polymorphisms and response in patients treated with panitumumab. Measures of EGFR protein and
      phosphoprotein expression by immunohistochemical- (IHC-) staining, K-ras mutation status1 and
      reverse-phase protein arrays (RPPA) and EGFR gene amplification by fluorescence in situ
      hybridization (FISH) will be assessed as exploratory correlates.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed diagnosis of locally
             recurrent or metastatic adenocarcinoma of the esophagus which is incurable with
             standard therapy.

          -  Patients must have measurable disease outside a previous radiation port, or which has
             developed in the port since the conclusion of radiation and is biopsy-proven to be
             recurrent cancer.

          -  One prior chemotherapy regimen for metastatic disease, with the exception of prior
             irinotecan or panitumumab.

          -  Prior radiation therapy to no more than 20% of the bone marrow is allowed. No
             treatment with wide field radiation within 4 weeks of entry onto this study.

          -  Full recovery from the effects of any prior surgery.

          -  Man or woman >18 years of age.

          -  ECOG performance status <2 (Karnofsky >60%)

          -  Life expectancy of >3 months

          -  Absolute neutrophil count (ANC) ≥ 1.5 x 109/L

          -  Platelet count ≥ 100 x 109/L

          -  Hemoglobin ≥ 9.0 g/dL

          -  Creatinine < or = to 1.5 mg/dL

          -  Creatinine clearance > or = to 50 mL/min calculated by the Cockcroft-Gault method as
             follows:

          -  Male creatinine clearance = (140 - age) x (weight in Kg) / (serum Cr x 72)

          -  Female creatinine clearance = (140 - age) x (weight in Kg) x 0.85 / (serum Cr x 72)

          -  Aspartate aminotransferase (AST) < or = to 3 x ULN (if liver metastases less than or
             equal to 5 x ULN)

          -  Alanine aminotransferase (ALT) < or = to 3 x ULN (if liver metastases less than or
             equal to 5 x ULN)

          -  Total bilirubin < or = to 1.5 x ULN

          -  Magnesium ≥ lower limit of normal

          -  Potassium > or = to lower limit of normal

          -  Because the effects of irinotecan and panitumumab on the developing human fetus are
             unknown, women of child-bearing potential and men must agree to use adequate
             contraception (hormonal or barrier method of birth control; abstinence) prior to study
             entry and for the duration of study participation.

        Exclusion Criteria:

          -  History or known presence of central nervous system (CNS) metastases unless CNS
             metastases have been irradiated and are stable.

          -  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 greater than or equal to 5 years prior to enrollment

          -  Pre-existing peripheral neuropathy > grade 1.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to panitumumab or irinotecan.

          -  Patients receiving any medications or substances that are established or probable
             inhibitors or inducers of P450 3A4 are ineligible.

          -  Prior anti-EGFr antibody therapy (eg, cetuximab) or treatment with small molecule EGFr
             inhibitors (eg, gefitinib, erlotinib, lapatinib)

          -  Radiotherapy < or = to 14 days prior to enrollment.

          -  Systemic chemotherapy, hormonal therapy, immunotherapy, or experimental or approved
             proteins/antibodies (or small molecules for Phase I studies) (eg, bevacizumab)< or =
             to 30 days before enrollment

          -  Subjects requiring chronic use of immunosuppressive agents (eg, methotrexate,
             cyclosporine)

          -  Any investigational agent or therapy < or = to 30 days before enrollment

          -  Prior therapy with Irinotecan or panitumumab.

          -  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.

          -  Women who test positive for serum or urine pregnancy test < 72 hours before
             randomization or is breast feeding

          -  Known positive test(s) for acute or chronic active hepatitis B infection

          -  Major surgery within 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 treatment and for six months after the
             last investigational product(s) administration

          -  Any underlying condition which in the opinion of the principal investigator will
             interfere with safety or with compliance with the study.