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Esophagus AdenocarcinomaPhase 2NCT05713838

Organ Preservation With Durvalumab-based Immunotherapy in Combination With Chemoradiation as Definitive Therapy for Early Stage Esophageal Adenocarcinoma With Indication for Radical Surgery

A Phase 2 study testing Durvalumab, FLOT and mFOLFOX-6 in people with Esophagus Adenocarcinoma, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 22 sites in Germany.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

The present clinical trial is a prospective, investigator-initiated, single-arm, open-label, multicenter phase II trial investigating whether a definite organ preservation therapy consisting of the combination of durvalumab with chemoradiation is an efficient and safe treatment option for early stage, cT1 and cT2N0… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Esophagus Adenocarcinoma
What is being tested?
Durvalumab, FLOT and mFOLFOX-6
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
22 sitesGermany
Study dates
28 Aug 2023to Dec 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • Patient has given written informed consent.
  • Patient is, in the investigator's judgement, willing and able to comply with the study protocol including the planned surgical treatment.
  • Patient is ≥ 18 years of age at time of signing the written informed consent.
  • Patient has been diagnosed with histologically confirmed esophageal adenocarcinoma (including gastroesophageal junction (GEJ) (Siewert I-III)) with:
  • cT2 N0 M0 stage or T1 N0 M0 stage and a given indication for radical surgical resection to current S3-guidelines (this includes patients with a given indication for radical surgery after endoscopic-resection of a cT1-2 N0 M0 tumor [poor grading or L1/V1 invasion or basal R1 resection or deep submucosal infiltration]) (see section 4.2.3 for detailed information).
  • tumor is considered medically and technically resectable.
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  • Tumor is tested (local testing with validated assays is sufficient, e.g., Dako PD-L1 IHC 22C3 or 28-8) for PD-L1 according to combined positive score (CPS) and results must be available prior study enrollment. In addition, tumor should be tested locally for MSI status and PD-L1 according to tumor proportion score (TPS) OR a representative tumor specimen that is suitable for central determination of PD-L1 TPS and MSI status is available. The analysis requires paraffin embedded biopsy samples of the tumor to be provided to the Sponsor.
  • NOTE: It is encouraged that CPS, TPS and MSI testing is performed in parallel locally at the trial site prior to enrollment, but at least CPS per local testing has to be available prior to enrollment.
  • Patient has not received prior cytotoxic or targeted therapy.
  • Patient has not had a prior complete esophagogastric tumor resection.
  • Patient has a ECOG ≤ 1.
  • Patient must have life expectancy of at least 12 weeks
  • Female patients of childbearing potential and male patients with female partners of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \<1% per year during the treatment period and for at least 6 months after the last study treatment if it is in the core treatment phase or for at least 3 months after last study treatment occurred in the maintenance phase. Male patients must refrain from donating sperm during this same period. Male patients with a pregnant partner must agree to remain abstinent or to use a condom for the duration of the pregnancy.
  • Patient has a body weight \> 30 kg
  • Patient has adequate hematological, hepatic and renal function as indicated by the following parameters:
  • Leukocytes ≥ 3,000/µL, platelets ≥ 100,000/µL without transfusion, absolute neutrophil count (ANC) ≥ 1,500/µL without granulocyte colony-stimulating factor support, hemoglobin ≥ 90 g/L (9 g/dL) - Patients may be transfused to meet this criterion.
  • Bilirubin ≤ 1.5 x upper limit of normal (ULN), aspartate transaminase and alanine transaminase ≤ 2.5 x ULN, alkaline phosphatase ≤ 2.5 x ULN
  • Serum creatinine ≤ 1.5 x ULN, or glomerular filtration rate \> 45 mL/min (calculated using the Cockcroft-Gault formula)
  • Serum albumin ≥ 25 g/L (2.5 g/dL)
  • For patients not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 x ULN; for patients receiving therapeutic anticoagulation: stable anticoagulant regimen
  • Patient has no human immunodeficiency virus (HIV) infection. NOTE: Patient with infection is eligible if he/she meets all the following criteria:
  • CD4 count is ≥350 cells/µL, viral load is undetectable, and not taking prohibited cytochrome (CYP)-interacting medications
  • Probable long-term survival with HIV if cancer were not present
  • Stable on a highly active antiretroviral therapy (HAART) regimen for ≥4 weeks and willing to adhere to their HAART regimen with minimal overlapping toxicity and drug-drug interactions with the experimental agents in this study
  • HIV is not multi-drug resistant
  • Taking medication and/or receiving antiretroviral therapy that does not interact or have overlapping toxicities with the study medication

Who cannot join

  • Patient has known hypersensitivity to any component of the durvalumab formulation as well as a known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion protein.
  • Patient has any known contraindication (including hypersensitivity) to docetaxel, 5-FU, leucovorin (calcium folinate), or oxaliplatin. In cases of pernicious anemia or other anemias due to vitamin B 12 deficiency, folinic acid (Leucovorin) is contraindicated and trial inclusion is not possible or only possible after compensation the anaemic status.
  • Patient has a known dihydropyrimidine dehydrogenase (DPD) deficiency. Patients with reduced DPD activity (CPIC activity score of 1.0-1.5) might participate in the study and receive a reduced dosage of 5-FU.
  • Patient has active or history of autoimmune disease including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
  • NOTE: History of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone, or controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible based on consultation with the sponsor's medical monitor. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all following conditions are met:
  • Rash must cover \< 10% of body surface area.
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  • Disease is well controlled at baseline and requires only low-potency topical corticosteroids.
  • No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months.
  • Patient had a prior allogeneic bone marrow transplantation or prior solid organ transplantation.
  • Patient has a history of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, idiopathic pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan.
  • NOTE: History of radiation pneumonitis within the radiation field (fibrosis) is permitted.
  • Patient has active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test prior to enrollment) or hepatitis C infection NOTE: Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction testing is negative for HCV ribonucleic acid (RNA).
  • Patient has active tuberculosis.
  • Patient has uncontrolled tumor-related pain (Patients requiring pain medication must be on a stable regimen at study entry.)
  • Patient received an administration of a live, attenuated vaccine within four weeks prior to start of enrollment, or anticipation that such a live attenuated vaccine will be required during the study or within 30 days after the last dose of durvalumab.
  • Patient had a prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA4, anti-PD-1, or anti-PD-L1 therapeutic antibodies.
  • Patient had a treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin-2) within four weeks or five half-lives of the drug, whichever is longer, prior to study enrollment.
  • Patient had a treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to initiation of study treatment. The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) is allowed
  • Intranasal, inhaled, topical steroids or local steroid injections (e.g. intra articular injection)
  • Systemic corticosteroids at physiologic dose not to exceed 10mg/day of prednisone or its equivalent
  • Steroids as premedication for hypersensitivity reactions (e.g. CT premedication)
  • Patient has a significant cardiovascular disease, such as cardiac disease (New York Heart Association Class II or greater), myocardial infarction or cerebrovascular accident within 3 months prior to initiation of study treatment, unstable arrhythmias, or unstable angina.
  • Patient has a clinically significant valvular defect.
  • Patient has a history of malignancy other than EGA within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g. 5-year OS rate \>90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.
  • Patient has peripheral polyneuropathy ≥ NCI CTCAE grade 2.
  • Patient has uncontrolled or symptomatic hypercalcemia (ionized calcium \> 1.5 mmol/L, calcium \> 12 mg/dL or corrected serum calcium \> ULN).
  • Patient has a serious infection requiring oral or IV antibiotics within 14 days prior to study enrollment.
  • Patient has chronic inflammatory bowel disease.
  • Patient has clinically significant active gastrointestinal bleeding.
  • Patient underwent major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment.
  • Patient has evidence of any other disease, neurologic or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of any of the study medications, puts the patient at higher risk for treatment-related complications or may affect the interpretation of study results.
  • Patient participated in another interventional clinical study ≤ 30 days prior to study enrollment or participation in such a study at the same time as this study.
  • Patient has taken an investigational drug within 28 days prior to initiation of study drug.
  • Female patients, who are pregnant or breast feeding or planning to become pregnant within and 6 months after the end of treatment. Female patients of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study treatment.

Trial locations and contacts

22 sites in 1 country.

22 sites in 1 country

Germany22 sites

  • Klinikum St. Marien Kommunalunternehmen - Anstalt des öffentlichen Rechts der Stadt Amberg

    Amberg

  • HELIOS Klinikum Bad Saarow

    Bad Saarow

  • Charite Univeristätsmedizin Berlin

    Berlin, 13353

  • Universitätsklinikum Brandenburg an der Havel Medizinische Hochschule Brandenburg

    Brandenburg an der Havel

  • Krankenhaus St. Joseph-Stift GmbH

    Bremen, 28209

  • Klinikum Darmstadt GmbH

    Darmstadt, 64283

  • Kliniken Essen Mitte Klinik für Internistische Onkologie und Hämatologie

    Essen

  • Institute of Clinical Cancer Research, University Cancer Center (UCT) Frankfurt Krankenhaus Nordwest

    Frankfurt

  • Universitätsmedizin Göttingen

    Göttingen, 37075

  • Universitätsklinikum Halle (Saale) Universitätsklinik und Poliklinik für Innere Medizin I

    Halle

  • Universitätsklinikum Heidelberg, RadioOnkologie & Strahlentherapie

    Heidelberg

  • St. Elisabeth Gruppe GmbH, St. Anna Hospital Herne

    Herne

  • Klinikverbund Allgäu gGmbH

    Kempten, 87439

  • Universitätsklinikum Schleswig-Holstein

    Kiel, 24105

  • ÜBAG - Medizinisches Versorgungszentrum Dr. Vehling-Kaiser GmbH

    Landshut, 84036

  • Klinikum Ludwigshafen gGmbH

    Ludwigshafen, 67063

  • Klinikum rechts der Isar der Technischen Universität München

    München

  • Gemeinschaftspraxis für Hämatologie und Onkologie GEHO

    Münster

  • Kreiskliniken Reutlingen GmbH Klinikum am Steinberg Reutlingen Ermstalklinik, Bad Urach

    Reutlingen

  • Leopoldina-Krankenhaus Medizinische Klinik II

    Schweinfurt

  • Klinikum Mutterhaus Trier

    Trier

  • Klinikum Wolfsburg

    Wolfsburg

Other trials in Germany

About this study

Official title: Organ Preservation With Durvalumab-based Immunotherapy in Combination With Chemoradiation as Definitive Therapy for Early Stage, cT1 and cT2N0, Esophageal Adenocarcinoma With Indication for Radical Surgery: A Prospective, Multicenter Study of the FLOT-AIO Gastric Cancer Group

The present clinical trial is a prospective, investigator-initiated, single-arm, open-label, multicenter phase II trial investigating whether a definite organ preservation therapy consisting of the combination of durvalumab with chemoradiation is an efficient and safe treatment option for early stage, cT1 and cT2N0, esophageal adenocarcinoma with indication for radical surgery.

Read the detailed description

Patients with early stage, cT1 and cT2N0 esophageal adenocarcinoma with indication for radical surgery (esophagectomy or transhiatal extended gastrectomy) will be enrolled in two cohorts according to their PD-L1 CPS (cohort 1 CPS < 10, cohort 2 CPS ≥ 10). All patients will receive core treatment consisting of immunotherapy with durvalumab in parallel to 2 cycles FLOT chemotherapy, followed by immunotherapy with durvalumab in parallel to 3 cycles of modified FOLFOX plus concomitant radiation (50 Gy). Eight weeks after this, patients will undergo tumor assessment consisting of esophagogastroduodenoscopy with extensive biopsies (bite-on-bite biopsies and fine-needle aspiration), endoscopic ultrasonography with measurement of maximum tumor thickness, and CT- or MRI-scans for tumor re-evaluation. Surgical resection would be offered only to those patients in whom a locoregional persistence is confirmed on tumor assessment, in the absence of any signs of distant dissemination. Patients with complete remission will enter the maintenance phase receiving durvalumab monotherapy for up to 12 cycles.

The primary objective of this trial is to investigate the treatment efficacy of the combination of durvalumab and chemoradiation as organ preservative treatment option avoiding mortality and surgical complications with rate of clinical and pathological complete response (cCR/pCR) at time of endoscopic re-evaluation defined as primary efficacy endpoint.

The secondary objectives are the further assessment of the efficacy of the combination of durvalumab and chemoradiation as organ preservative treatment option 1-/2- and 3-year cCR/pCR rate, rate of salvage surgery, 90-day and 1-year mortality as secondary endpoints and to assess the quality of life (QoL).

Being tested
Durvalumab, FLOT, mFOLFOX-6, Radiotherapy
Keywords
esophageal adenocarcinoma, GEJ adenocarcinoma
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.

  • DurvalumabDrug

    Also called IMFINZI

    1500 mg Durvalumab, IV, day 1 Q4W (max. 15 cycles)

  • FLOTDrug

    50 mg/m² docetaxel, 85 mg/m² oxaliplatin, 200 mg/m² calcium folinate and 2600 mg/m² fluorouracil as 24 h-infusion, 2 cycles

  • mFOLFOX-6Drug

    85 mg/m² oxaliplatin, 200 mg/m² calcium folinate, 400 mg/m² fluorouracil as bolus dose and 1600 mg/m² fluorouracil as 48 h-infusion, ² cycles

  • RadiotherapyRadiation

    5 weeks with 5 days a week radiotherapy (25 daily fractions with 2.0 Gy = ∑50Gy)

Study groups in NCT05713838
Study groupRoleWhat they receive
Durvalumab + ChemoradiotherapyExperimentalCore Treatment: * D1: Durvalumab (1500 mg, IV) PLUS FLOT (50 mg/m² docetaxel, 85 mg/m² oxaliplatin, 200 mg/m² calcium folinate and 2600 mg/m² 5-FU 24h) * D15: FLOT (50 mg/m² docetaxel, 85 mg/m² oxaliplatin, 200 mg/m² calcium folinate and 2600 mg/m² 5-FU 24h), * D29: Durvalumab (1500 mg, IV) PLUS mFOLFOX (85 mg/m² oxaliplatin, 200 mg/m² calcium folinate, 400 mg/m² 5-FU bolus and 1600 mg/m² 5-FU 48h) PLUS 50 Gy radiotherapy * 5 weeks with 5 days a week radiotherapy (25 daily fractions, 2.0 Gy = ∑50Gy) * D43: mFOLFOX (85 mg/m² oxaliplatin, 200 mg/m² calcium folinate, 400 mg/m² 5-FU bolus, 1600 mg/m² 5-FU 48h) (radiation cont.) * D57: Durvalumab (1500 mg, IV) PLUS mFOLFOX (85 mg/m² oxaliplatin, 200 mg/m² calcium folinate, 400 mg/m² 5-FU bolus and 1600 mg/m² 5-FU 48h) (radiation cont.) Maintenance Phase Durvalumab monotherapy max. 12 cycles à 4 weeks: Durvalumab (1500 mg, IV, Q4W) D1
Receives: Drug: Durvalumab; Drug: FLOT; Drug: mFOLFOX-6; Radiation: Radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of clinical and pathological complete response (cCR/pCR)

    Rate of clinical and pathological complete response rate at time of endoscopic re-evaluation (at the end of the core study treatment) according to Becker criteria and investigator-based RECIST v1.1 assessment as well as endoscopic response criteria similar to the Japanese Gastric Cancer Association Guideline

    Measured: 8 weeks after completion of core treatment

Secondary outcomes (6)

  1. Rate of cCR/pCR (long term follow up)

    Rate of cCR/pCR at 1, 2 and 3 years after start of treatment (long term follow up)

    Measured: 1, 2 and 3 years after start of treatment

  2. Subgroup analysis of cCR/pCR

    Subgroup analysis of cCR/pCR rate at time of endoscopic re-evaluation and after 1 year according to following characteristics: MSI high, PD-L1 CPS>1 and PD-L1 CPS>5 and especially acc. to CPS ≥10 or <10

    Measured: 8 weeks after completion of core treatment and after 1 year

  3. Rate of salvage surgery

    Rate of salvage surgery

    Measured: up to 48 months

  4. Mortality

    90-day as well as 1-year mortality after start of treatment in non-surgery population and population with salvage surgery

    Measured: 90 days, 12 months after start of treatment

  5. Determination of the sites of tumor relapse

    Determination of the sites of tumor relapse

    Measured: up to 48 months

  6. Safety Endpoints

    Incidence of adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs) as assessed during treatment and until 90 days after the last dose of study drug

    • Severity of adverse events by CTCAE v5.0 grade
    • Relationship of adverse events to the durvalumab, chemotherapy and/or radiation
    • Frequency of clinically significant abnormal laboratory parameters to CTCAE (Common Terminology Criteria for Adverse Events)

    Measured: up to 20 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Feb 2023
  2. Study start28 Aug 2023
  3. Primary completion1 Jan 2027 (estimated)
  4. Study completionDec 2028 (estimated)

Resources

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
Not applicable
Intervention model
Single group
Model description
Patients eligible for this trial will be enrolled into one of two cohorts: Cohort 1 will consist of participants with PD-L1 combined positive score (CPS) \< 10. Cohort 2 will consist of participants with PD-L1 CPS ≥ 10. Patients in both cohorts will receive immunotherapy with durvalumab in parallel to 2 cycles FLOT chemotherapy induction followed by immunotherapy with durvalumab in parallel with 3 cycles of modified FOLFOX chemotherapy plus concomitant radiation (50 Gy). After initial core treatment and endoscopic re-evaluation patients with complete remission will receive durvalumab monotherapy (1500 mg, IV, Q4W) for a maximum of 12 cycles. Patients in whom a locoregional persistence is confirmed will be offered surgical resection instead of entering the the maintenance period.
Masking
None (open label)
Enrolment
32 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05713838
Sponsor's protocol ID
PRESTO
Status last verified
Aug 2026
First submitted
26 Jan 2023
Last updated
7 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Durvalumab, FLOT and mFOLFOX-6 in people with Esophagus Adenocarcinoma, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 22 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 26 inclusion and 34 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: under way, not looking for participants, as of the sponsor's last update on 7 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 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?

This study is still under way. Results are not available in the source record yet.

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?

Rate of clinical and pathological complete response (cCR/pCR) (time frame: 8 weeks after completion of core treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05713838.

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 7 Aug 2026.

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