A Study of Durvalumab (MEDI4736) in Esophageal Cancer

NCT02639065 | Completed Phase 2 Results DMC

• 1 other identifier: BTCRC-ESO14-012
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Esophageal Cancer

Keywords

Durvalumab; MEDI4736; PD-L1 inhibitor

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With One-Year Relapse Free Survival (RFS) With Post-Operative Durvalumab

  Relapse free survival is defined as time from the date of surgery until the criteria for disease relapse is met, per Response Evaluation Criteria In Solid Tumors (RECIST 1.1), or death occurs. Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started The percentage of subjects who attained relapse free survival for 1 year and 95 % confidence interval has been reported here.

  From the date of surgery until disease relapse or death up to a maximum of 40 months.

Secondary Outcomes (1)

• Number of Patients With Adverse Events as a Measure of Safety and Tolerability

  From the time of consent until 90 days after last dose of durvalumab up to a maximum of 15 months.

Study Arms (1)

Investigational Treatment

EXPERIMENTAL

Durvalumab 1500 mg IV every 4 weeks (1 cycle) for a maximum 13 doses (12 months), or until unacceptable toxicities or disease recurrence.

Drug: Durvalumab

Interventions

Durvalumab DRUG

1500 mg IV every 4 weeks (1 cycle) for a maximum 13 doses (12 months), or until unacceptable toxicities or disease recurrence.

Also known as: MEDI4736

Investigational Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shadia Jalal, MD: lead
• MedImmune LLC: collaborator
• AstraZeneca: collaborator
• Big Ten Cancer Research Consortium: collaborator

Study Sites (3)

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Unversity of Iowa Hospital and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (1)

• Mamdani H, Schneider B, Perkins SM, Burney HN, Kasi PM, Abushahin LI, Birdas T, Kesler K, Watkins TM, Badve SS, Radovich M, Jalal SI. A Phase II Trial of Adjuvant Durvalumab Following Trimodality Therapy for Locally Advanced Esophageal and Gastroesophageal Junction Adenocarcinoma: A Big Ten Cancer Research Consortium Study. Front Oncol. 2021 Sep 17;11:736620. doi: 10.3389/fonc.2021.736620. eCollection 2021.

  PMID: 34604072 DERIVED

Related Links

• Big Ten Cancer Research Consortium Website

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Results Point of Contact

• Title: Annesha Majumdar
• Organization: Hoosier Cancer Research Network

amajumdar@hoosiercancer.org

3179212050

Study Officials

• Shadia Jalal, M.D.

  Big Ten Cancer Research Consortium

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: December 21, 2015
• First Posted: December 24, 2015
• Study Start: April 27, 2016
• Primary Completion: December 9, 2020
• Study Completion: June 9, 2021
• Last Updated: September 25, 2023
• Results First Posted: June 1, 2022

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)