A Study of Durvalumab (MEDI4736) in Esophageal Cancer
Condition: Esophageal Cancer
MeSH terms: Esophageal Neoplasms
Intervention: Durvalumab
Intervention description: 1500 mg IV every 4 weeks (1 cycle) for a maximum 13 doses (12 months), or until unacceptable toxicities or disease recurrence.
Intervention MeSH terms: Durvalumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Masking description: Open Label
Enrollment: 39.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Durvalumab; MEDI4736; PD-L1 inhibitor

Summary:

      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
      as:

        -  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
           durvalumab.
    

Eligibility criteria:

        Inclusion Criteria:

        Subject must meet all of the following applicable inclusion criteria to participate in this
        study:

          -  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
             therapy.

          -  Females of childbearing potential and males must be willing to use two effective
             methods of contraception (see the protocol) from the time consent is signed until 3
             months 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. See the
             protocol.

          -  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
             Pathologists Guidelines):

               -  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
             up.

        Exclusion Criteria:

        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
             therapy.

          -  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,
             ulcerative colitis).

          -  Presence of interstitial lung disease or history of pneumonitis requiring treatment
             with corticosteroids.

          -  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
             corticosteroid.

          -  History of allogeneic organ or stem cell transplant.

          -  Receipt of live attenuated vaccine within 30 days prior to registration for protocol
             therapy.

          -  Mean QT interval corrected for heart rate (QTc) > 470 msec calculated from 3 ECGs by
             Bazett's Correction.

          -  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
             consent.

          -  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
             protocol therapy.

          -  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.