Esophageal AdenocarcinomaPhase 2RICENCT04159974
RICE: Radio-Immuno-Chemotherapy of Cancer of the Esophagus
A Phase 2 study testing Durvalumab 50 MG/ML and Tremelimumab in people with Esophageal Adenocarcinoma, run by University of Cologne at 2 sites in Germany.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Esophageal Adenocarcinoma
- What is being tested?
- Durvalumab 50 MG/ML and Tremelimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 2 sitesGermany
- Study dates
- 30 Sep 2019to Jun 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- 1. 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.
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- 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)
- Females:
- Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL)
- AST/ALT (SGOT/SGPT) ≤ 2,5 x institutional ULN Total Bilirubin ≤ 1.5 x institutional ULN (except study participants with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
- Body weight > 30kg
- Reproductive Status Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception and must agree to use adequate method to avoid pregnancy for 5 months (30 days plus the time required for durvalumab to undergo five half-lives) after the last dose of study drug.
- Appropriate methods of contraception are:
- female sterilization or tubal ligation (at least 6 weeks prior to the start of the study treatment),
- male sterilization (at least 6 months prior to the start of the study treatment) and/or
- a combination of a hormonal method of contraception with a barrier method or/and
- an intrauterine device or system
- Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of β-HCG) within one until two weeks prior to the start of durvalumab at time of neoadjuvant treatment and after surgery before starting adjuvant treatment.
- Women will be not be considered to be of childbearing potential if they are post-menopausal and/or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy). To be considered post-menopausal the appropriate age-specific requirements have to be met:
- Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution.
- Women ≥ 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago.
- Women must not be breastfeeding.
- Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving durvalumab and who are sexually active with WOCBP must be willing to adhere to contraception for a period of 7 month post treatment completion.
- Sexually active men receiving durvalumab must use a condom, even if vasectomized, to prevent delivery of the drug via seminal fluid.
Who cannot join
- 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
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- 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
- Pregnancy or breastfeeding females
- Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy or 180 days after the last dose of durvalumab + tremelimumab combination therapy.
- Allergies and Adverse Drug Reaction:
- History of allergy to study drug components History of severe hypersensitivity reaction to any monoclonal antibody
- Current treatment within another therapeutic clinical trial with experimental and not approved drugs and treatment combinations.
Trial locations and contacts
2 sites in 1 country.
Germany2 sites
University of Cologne
Cologne, 50937
Klinikum der Universität München
München, 81377
About this study
Official title: 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
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
Read the detailed description
Short Study Title: RICE - Radio-Immuno-Chemotherapy of Cancer of the Esophagus
Study Phase: Phase II
Research hypothesis: The investigators aim at evaluating if (I) esophageal cancer is susceptible to immunotherapeutic approaches based on interference with the PD1 / PDL1 axis, if (II) treatment of locally advanced tumors by immunotherapeutic approaches increases cure rate and if (III) combination with radiotherapy is feasible and increases anti-tumor immunity.
Primary Objectives: 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).
- Conditions
- Esophageal Adenocarcinoma
- Being tested
- Durvalumab 50 MG/ML, Tremelimumab
- Medical subject headings
- Adenocarcinoma Of Esophagus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Durvalumab 50 MG/MLDrug
IV Infusion
TremelimumabDrug
IV Infusion, Combination with Durvalumab
| Study group | Role | What they receive |
|---|---|---|
| Durvalumab | Experimental | Treatment arm A will receive durvalumab IV in a dosage of 1500mg every four weeks for 12 months as mono therapy. Receives: 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). Receives: Drug: Durvalumab 50 MG/ML; Drug: Tremelimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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
To determine the Best Objective Response (BOR) as defined by RECIST 1.1 and iRECIST criteria after neoadjuvant treatment
Measured: 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
To determine Progression Free Survival (PFS) in durvalumab vs. durvalumab + tremelimumab adjuvant treatment.
PFS is defined as PFS from treatment start to first detection of disease progression.
Measured: Until 24 months after the end of treatment
Determination of Disease Free Survival (DFS) in durvalumab vs. durvalumab + tremelimumab adjuvant treatment
To determine Disease Free Survival (DFS) in durvalumab vs. durvalumab + tremelimumab adjuvant treatment.
DFS is defined as DFS from time of surgery to first detection of disease progression.
Measured: Until 24 months after the end of treatment
Determination of Overall Survival (OS) in durvalumab vs. durvalumab + tremelimumab adjuvant treatment
To determine Overall Survival (OS) in durvalumab vs. durvalumab + tremelimumab adjuvant treatment.
OS is defined as OS from treatment start to death.
Measured: 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
To assess the subject's esophageal-cancer-related quality of life using the Functional Assessment of Cancer Therapy-Esophageal (FACT-E) questionnaire.
The questionnaire will be done by interview administration at screening, visit 5 during neoadjuvant treatment, before surgery, after randomization before start of adjuvant treatment and after then every 12 weeks at the time of tumor staging also in the follow-up phase.
Measured: Until 24 months after the end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2019
- Study start30 Sep 2019
- Primary completionJun 2024 (estimated)
- Study completionJun 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Esophageal AdenocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 56 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Cologne
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Principal investigator, Thomas Zander, University of Cologne
- Investigators
- Thomas Zander, Prof. Dr. med, Principal investigator, University of Cologne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04159974
- Sponsor's protocol ID
- UNI-Koeln-3571
- Other IDs
- DRKS00015218, 2018-003048-22, 2018
- Acronym
- RICE
- Status last verified
- May 2023
- First submitted
- 23 Oct 2019
- Last updated
- 9 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04159974
- Acronym / sponsor ID
- RICE / UNI-Koeln-3571
- Conditions
- Esophageal Adenocarcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 56 participants (estimated)
- Lead sponsor
- University of CologneUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- 30 Sep 2019 (actual)
- Primary completion
- Jun 2024 (estimated)
- Study completion
- Jun 2024 (estimated)
- First posted
- 12 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
Short Study Title: RICE - Radio-Immuno-Chemotherapy of Cancer of the Esophagus
Study Phase: Phase II
Research hypothesis: The investigators aim at evaluating if (I) esophageal cancer is susceptible to immunotherapeutic approaches based on interference with the PD1 / PDL1 axis, if (II) treatment of locally advanced tumors by immunotherapeutic approaches increases cure rate and if (III) combination with radiotherapy is feasible and increases anti-tumor immunity.
Primary Objectives: 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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Durvalumab | Experimental | Drug: Durvalumab 50 MG/MLTreatment arm A will receive durvalumab IV in a dosage of 1500mg every four weeks for 12 months as mono therapy. |
| Durvalumab + Tremelimumab | Experimental | Drug: Durvalumab 50 MG/ML, Drug: TremelimumabTreatment 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (32 listed)
- Signed Written Informed Consent
- Target Population
- 1. Histologically confirmed, resectable adenocarcinoma of the esophagus or cardia/gastric esophageal junction (uT3, cNx, cM0), with the following specifications:
- Male or female patients ≥ 18 years of age at time of study entry
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
Key exclusion criteria (20 listed)
- 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:
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Durvalumab 50 MG/MLIV Infusion | Drug | Durvalumab, Durvalumab + Tremelimumab |
| TremelimumabIV Infusion, Combination with Durvalumab | Drug | Durvalumab + Tremelimumab |
Primary outcome
Evaluation of Safety and efficacy (measured by an increase of pathological complete response rate)
Time frame: Calculated once at the end of study (24 months after the end of treatment)
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).
5 secondary outcomes
Determination of Best Objective Response (BOR) as defined by RECIST 1.1 and iRECIST criteria after neoadjuvant treatment
Time frame: 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
Time frame: Until 24 months after the end of treatment
Determination of Disease Free Survival (DFS) in durvalumab vs. durvalumab + tremelimumab adjuvant treatment
Time frame: Until 24 months after the end of treatment
Determination of Overall Survival (OS) in durvalumab vs. durvalumab + tremelimumab adjuvant treatment
Time frame: 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
Time frame: Until 24 months after the end of treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas Zander, Prof. Dr. med principal investigator
University of Cologne
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Durvalumab 50 MG/ML and Tremelimumab in people with Esophageal Adenocarcinoma, run by University of Cologne at 2 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 32 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluation of Safety and efficacy (measured by an increase of pathological complete response rate) (time frame: Calculated once at the end of study (24 months after the end of treatment)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2024.