This is a phase II, open-label, single arm, single-stage study. A total of 23 evaluable
patients will be enrolled. If total number of patients free of disease relapse at 1 year is
less than or equal to 15, the drug would not be considered for further study in this setting.
After six patients are treated with at least one dose of study drug, they will be observed
for a minimum of 60 days. During the 60-day observation period, further accrual will be
halted to evaluate "unacceptable toxicities warranting early closure of the trial" defined
- Any definitive durvalumab-related death. A durvalumab-related death will be continuously
monitored throughout the trial and the trial will be suspended for re-evaluation
whenever such an event is confirmed.
- Any unexpected and previously unreported grade 4 toxicities definitely related to
OUTLINE: This is a multi-center trial.
Subjects will receive durvalumab 1500 mg IV every 4 weeks (1 cycle) for a maximum 13 doses
(12 months), or until unacceptable toxicities or disease recurrence.
The following baseline labs must be completed within 28 days prior to registration for
- White blood cell count (WBC) > 3 K/mm^3
- Hemoglobin (Hgb) > 9 g/dL. Transfusion is allowed, if needed, since patients are post
- Platelets > 100 K/mm^3
- Absolute neutrophil count (ANC) ≥ 1.5 K/mm^3
- Calculated creatinine clearance of >/= 40 cc/min using the Cockcroft-Gault formula or by
24-hour urine collection.
- Bilirubin ≤ 1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST, SGOT) </= 2.5 x ULN
- Alanine aminotransferase (ALT, SGPT) </= 2.5 x ULN
Subject must meet all of the following applicable inclusion criteria to participate in this
- Written informed consent and HIPAA authorization for release of protected health
information obtained from the subject prior to performing any protocol-related
procedures, including screening evaluations. NOTE: HIPAA authorization may be included
in the informed consent or obtained separately.
- Age ≥ 18 years at the time of consent.
- ECOG Performance Status of 0-1 within 28 days prior to registration for protocol
- Females of childbearing potential and males must be willing to use an effective method
of contraception (hormonal or barrier method of birth control; abstinence) from the
time consent is signed until 12 weeks after treatment discontinuation.
- Females of childbearing potential must have a negative serum pregnancy test within 14
days prior to registration for protocol therapy. NOTE: Female subjects are considered
of child bearing potential unless they are surgically sterile (they have undergone a
hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are ≥60
years old and naturally postmenopausal for at least 12 consecutive months.
- Histological evidence of persistent residual esophageal adenocarcinoma including
gastroesophageal junction adenocarcinoma following definitive concurrent
chemoradiotherapy (carboplatin and paclitaxel or cisplatin and 5-FU) in the surgical
sample (esophagus or lymph node or both) obtained at the time of esophagectomy. NOTE:
Persistent residual disease is defined as follows (modified from College of American
- No residual tumor (Grade 0, complete response, 0% tumor). This group will not be
included in this study.
- Marked response (Grade 1, 0-<10% residual tumor)
- Moderate response (Grade 2, 10-50% residual tumor)
- No definite response (Grade 3, >50% residual tumor)
- Minimum of 1 month and maximum of 3 months from surgical resection with no evidence of
disease progression at the time of enrollment.
- Must have adequately recovered from surgery as judged by the treating investigator.
- Subject is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations including follow
Subjects meeting any of the criteria below may not participate in the study:
- Prior therapy with a PD-1, PD-L1, or CTLA-4 inhibitor or cancer-specific vaccine
- Evidence of active autoimmune disease requiring systemic treatment within preceding 3
months or a documented history of clinically severe autoimmune disease, or a syndrome
that requires systemic steroids or immunosuppressive agents. Exceptions to this rule
include vitiligo, resolved childhood asthma/atopy, requirement of intermittent
bronchodilators or local steroid injections, hypothyroidism stable on hormone
replacement, psoriasis not requiring systemic treatment (within the past 2 years),
Graves's disease and Sjogren's syndrome.
- Prior malignancy is not allowed except for adequately treated basal cell or squamous
cell skin cancer, in situ cervical cancer, Gleason score ≤ 7 prostate cancers, or
other cancer for which the subject has been disease-free for at least 3 years.
- Active or prior documented inflammatory bowel disease (e.g. Crohn's disease,
- Presence of interstitial lung disease or history of pneumonitis requiring treatment
- Patients with diagnosis of primary immunodeficiency.
- Patients receiving chronic systemic corticosteroid therapy or other immunosuppressive
therapy within 28 days prior to registration for protocol therapy. Exceptions include
intranasal and inhaled corticosteroids or systemic corticosteroids at physiological
doses, which are not to exceed 10 mg/day of prednisone, or an equivalent
- History of allogeneic organ or stem cell transplant.
- Receipt of live attenuated vaccine within 30 days prior to registration for protocol
- Mean QT interval corrected for heart rate (QTc) > 470 msec calculated from 3 ECGs by
- Ventricular arrhythmias requiring medication(s).
- Uncontrolled intercurrent illness including, but not limited to, symptomatic
congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac
arrhythmia, active peptic ulcer disease or gastritis, or active bleeding diatheses.
- History of psychiatric illness/social situations that would limit compliance with
study requirements or compromise the ability of the subject to give written informed
- Known HIV infection or chronic hepatitis B or C.
- Known history of previous clinical diagnosis of tuberculosis.
- Clinically significant infections as judged by the treating investigator. Clinically
significant is defined as an active infection requiring IV antibiotics.
- Because there is an unknown but potential risk for adverse events in nursing infants
secondary to treatment of the mother, breastfeeding should be discontinued. In
addition, breast milk cannot be stored for future use while the mother is being
treated on study.
- Treatment with any investigational agent within 28 days prior to registration for
- History of hypersensitivity to durvalumab or any excipient.
- Any condition that, in the opinion of the investigator, would interfere with
evaluation of study treatment or interpretation of patient safety or study results.
- Previous enrollment in the present study.