Clinical Trials /

A Study of Durvalumab (MEDI4736) in Esophageal Cancer

NCT02639065

Description:

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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Esophageal Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Durvalumab (MEDI4736) in Esophageal Cancer
  • Official Title: A Phase II Study Evaluating Safety and Efficacy of Durvalumab (MEDI4736) Following Multi-modality Therapy in Esophageal Cancer: Big Ten Cancer Research Consortium BTCRC-ESO14-012

Clinical Trial IDs

  • ORG STUDY ID: BTCRC-ESO14-012
  • NCT ID: NCT02639065

Conditions

  • Esophageal Cancer

Interventions

DrugSynonymsArms
DurvalumabMEDI4736Investigational Treatment

Purpose

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.

Detailed Description

      OUTLINE: This is a multi-center trial.

      INVESTIGATIONAL TREATMENT:

      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
      protocol therapy:

      Hematopoietic:

        -  White blood cell count (WBC) > 3 K/mm^3

        -  Hemoglobin (Hgb) > 9 g/dL. Transfusion is allowed, if needed, since patients are post
           esophagectomy.

        -  Platelets > 100 K/mm^3

        -  Absolute neutrophil count (ANC) ≥ 1.5 K/mm^3

      Renal:

        -  Calculated creatinine clearance of >/= 40 cc/min using the Cockcroft-Gault formula or by
           24-hour urine collection.

      Hepatic:

        -  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
    

Trial Arms

NameTypeDescriptionInterventions
Investigational TreatmentExperimentalDurvalumab 1500 mg IV every 4 weeks (1 cycle) for a maximum 13 doses (12 months), or until unacceptable toxicities or disease recurrence.
  • 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 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
             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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:One-Year Relapse Free Survival (RFS) Rates with Post-Operative Adjuvant Durvalumab
Time Frame:Assessed at one year post-surgery
Safety Issue:
Description:RFS defined as time from the date of surgery until criteria for disease relapse is met, per Response Evaluation Criteria In Solid Tumors (RECIST 1.1), or death occurs

Secondary Outcome Measures

Measure:Number of Patients with Adverse Events as a Measure of Safety and Tolerability
Time Frame:From time of consent and up to 90 days after treatment discontinuation (est. 15 months)
Safety Issue:
Description:Assess toxicity and tolerability of durvalumab following trimodality therapy, per Common Terminology Criteria for Adverse Events (CTCAE) v4

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Shadia Jalal, MD

Trial Keywords

  • Durvalumab
  • MEDI4736
  • PD-L1 inhibitor

Last Updated

April 17, 2020