Overview

Phase II Study of Irinotecan and Panitumumab

Status:
Completed
Trial end date:
2015-08-01
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Weijing Sun, MD, FACP
Collaborator:
Amgen
Treatments:
Antibodies, Monoclonal
Camptothecin
Irinotecan
Panitumumab
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.