RICE: Radio-Immuno-Chemotherapy of Cancer of the Esophagus

NCT04159974 | Unknown Phase 2

• 3 other identifiers: UNI-Koeln-3571DRKS000152182018-003048-22
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 2

Brief Summary

A phase II trial to evaluate safety and efficacy of adding durvalumab (MEDI4736) to standard neoadjuvant radiochemotherapy and of adjuvant durvalumab +/- tremelimumab in locally advanced esophageal adenocarcinoma and to evaluate biomarkers predictive for response to immune checkpoint inhibition

Conditions

Esophageal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Evaluation of Safety and efficacy (measured by an increase of pathological complete response rate)

  The primary objective is to evaluate safety and efficacy (measured by an increase of pathological complete response rate from 20% to 35%) of the fully human monoclonal IgG1 antibody durvalumab targeting the programmed death-ligand 1 (PD-L1) in combination with neoadjuvant radiochemotherapy, followed by surgery for locally advanced esophageal cancer and cancer of the gastric esophageal junction (GEJ).

  Calculated once at the end of study (24 months after the end of treatment)

Secondary Outcomes (5)

• Determination of Best Objective Response (BOR) as defined by RECIST 1.1 and iRECIST criteria after neoadjuvant treatment

  Determined once after neoadjuvant treatment (up to 12 weeks after study start)

• Determination of Progression Free Survival (PFS) in durvalumab vs. durvalumab + tremelimumab adjuvant treatment

  Until 24 months after the end of treatment

• Determination of Disease Free Survival (DFS) in durvalumab vs. durvalumab + tremelimumab adjuvant treatment

  Until 24 months after the end of treatment

• Determination of Overall Survival (OS) in durvalumab vs. durvalumab + tremelimumab adjuvant treatment

  From the study start until the date of death, assessed up to 240 months

• Assessment of the subject's esophageal-cancer-related quality of life using the Functional Assessment of Cancer Therapy-Esophageal (FACT-E) questionnaire

  Until 24 months after the end of treatment

Study Arms (2)

Durvalumab

EXPERIMENTAL

Treatment arm A will receive durvalumab IV in a dosage of 1500mg every four weeks for 12 months as mono therapy.

Drug: Durvalumab 50 MG/ML

Durvalumab + Tremelimumab

EXPERIMENTAL

Treatment arm B receives durvalumab in a dosage of 1500mg every 4 weeks (-3/+7 days) for 12 months post-surgery. In addition these patients receive tremelimumab IV in a fixed dose of 75mg for the first four months on day 1; 29; 57; 85 (-3/+7).

Drug: Durvalumab 50 MG/ML; Drug: Tremelimumab

Interventions

Durvalumab 50 MG/ML DRUG

IV Infusion

Durvalumab; Durvalumab + Tremelimumab

Tremelimumab DRUG

IV Infusion, Combination with Durvalumab

Durvalumab + Tremelimumab

Eligibility Criteria

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

You may qualify if:

• Signed Written Informed Consent
• Study participants must have signed and dated an IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal study participant care.
• Study participants must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests and other requirements of the study.
• Target Population
• \. Histologically confirmed, resectable adenocarcinoma of the esophagus or cardia/gastric esophageal junction (uT3, cNx, cM0), with the following specifications:
• Medical and technical operability, according to the techniques described in Section 2.1.3.2.
• No preceding cytotoxic or targeted therapy
• No prior partial or complete tumor resection
• Male or female patients ≥ 18 years of age at time of study entry
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
• Life expectancy of at least 12 months
• Study participants must be willing to undergo at least 2 biopsies (baseline and after neoadjuvant treatment and optional in progression)
• Adequate normal organ and marrow function as defined below. Screening laboratory values must meet the following criteria and should be obtained within 28 days prior to registration WBC ≥ 1500/μL Neutrophils ≥ 1000/μL Platelets ≥ 75 x103/μL Hemoglobin \> 9.0 g/dL Serum creatinine ≤ 1.5 x institutional ULN or calculated creatinine clearance (CrCl) ≥ 40 mL/min (Cockcroft-Gault)
• Males:
• Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL)

You may not qualify if:

• Study participants with squamous cell carcinoma of the esophagus
• Prior treatment with chemotherapy, targeted therapy or radiotherapy for treatment of advanced cancer disease less than 5 years
• Enrollment is possible for patients with:
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease
• Any other serious or uncontrolled medical disorder, active infections, physical exam findings, laboratory finding, altered mental status, or psychiatric condition that, in the opinion of the investigator, would limit a study participant's ability to comply with the study requirements, substantially increase risk to the study participant, or impact the interpretability or study results
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement Any chronic skin condition that does not require systemic therapy Patients without active autoimmune or inflammatory disease in the last 5 years may be included but only after consultation with study physician Patients with celiac disease controlled by diet alone. Inhaled or topical steroids and adrenal replacement steroid doses \> 10mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.
• History of active primary immunodeficiency
• History of any allogenic organ transplantation with currently intake of immune suppressive treatment
• Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• Patients with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity. FEV 1 \< 75%
• Patients has known current symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
• Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
• Prisoners or study participants who are involuntarily incarcerated

Sponsors & Collaborators

• University of Cologne: lead
• AstraZeneca: collaborator

Study Sites (2)

University of Cologne

Cologne, 50937, Germany

Location

Klinikum der Universität München

München, 81377, Germany

Location

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus

Interventions

durvalumab; tremelimumab

Study Officials

• Thomas Zander, Prof. Dr. med

  University of Cologne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 23, 2019
• First Posted: November 12, 2019
• Study Start: September 30, 2019
• Primary Completion: June 1, 2024
• Study Completion: June 1, 2024
• Last Updated: May 9, 2024

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2)