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AzTrials

Gastric CancerPhase 2DANTENCT03421288

Study of Atezolizumab + FLOT vs. FLOT Alone in Patients With GC/GEJ and High Immune Responsiveness

A Phase 2 study testing Atezolizumab, 5-Fluorouracil and Calciumfolinat in people with Gastric Cancer and Gastroesophageal Junction Adenocarcinoma, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 2 sites in 2 countries.

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

This is a multicenter, randomized, controlled, open-label study comparing perioperative atezolizumab with FLOT chemotherapy versus FLOT alone in patients with locally advanced, operable adenocarcinoma of the stomach or GEJ with high immune responsiveness. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Atezolizumab, 5-Fluorouracil and Calciumfolinat
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
677 participants
Where
2 sitesin 2 countries
Study dates
14 Sep 2018to 31 Dec 2027
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

  • Have provided written informed consent
  • In the investigator's judgement, is willing and able to comply with the study protocol including the planned surgical treatment
  • Female and male patients* ≥ 18 years of age
  • Diagnosed with histologically confirmed adenocarcinoma of the GEJ (Type I-III) or the stomach (cT2, cT3, cT4, any N category, M0), or (any T, N+, M0) that:
  • is not infiltrating any adjacent organs or structures by CT or MRI evaluation
  • does not involve peritoneal carcinomatosis
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  • is considered medically and technically resectable Note: the absence of distant metastases must be confirmed by CT or MRI of the thorax and abdomen, and, if there is clinical suspicion of osseous lesions, a bone scan. If peritoneal carcinomatosis is suspected clinically, its absence must be confirmed by laparoscopy. Diagnostic laparoscopy is mandatory in patients with T3 or T4 tumors of the diffuse type histology in the stomach.
  • No prior cytotoxic or targeted therapy
  • No prior partial or complete esophagogastric tumor resection
  • ECOG ≤ 1
  • Phase II only: Availability of a representative tumor specimen that is suitable for determination of PD-L1 and MSI status; MSI assessment will be performed locally or centrally, and result must be available prior to randomization (for details, see chapter 9.1). PD-L1 will be assessed centrally but is not used for enrolment of the patients. The analysis requires paraffin embedded biopsy samples of the tumor.
  • Phase III only: Assessment of MSI and PD-L1 [and optional TMB/EBV] must be performed locally and results for either of the following MSI-high, PD-L1 CPS≥1, TMB ≥10/MB or EBV+ must be available prior to randomization (for details, see chapter 9.2).
  • Females 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 5 months after the last study treatment. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (has not had ≥12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal implants, established, proper use of combined oral or injected hormonal contraceptives, and certain intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
  • Males must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agree to refrain from donating sperm, as defined below:
  • With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of 1% per year during the treatment period and for at least 3 months after the last dose of study treatment to avoid exposing the embryo. Men must refrain from donating sperm during this same period. Men with a pregnant partner must agree to remain abstinent or to use a condom for the duration of the pregnancy.
  • Criterion integrated in criterion 9.
  • Adequate hematological, hepatic and renal function as indicated by the following parameters:
  • Leukocytes ≥ 3.000/mm³, platelets ≥ 100.000/mm3without transfusion, absolute neutrophil count (ANC) ≥ 1500/mm3without 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, aspartate transaminase and alanine transaminase ≤ 2.5 x upper limit of normal, alkaline phosphatase ≤ 2.5 x upper limit of normal
  • Serum creatinine ≤ 1.5 x upper limit of normal, 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 *There are no data that indicate special gender distribution. Therefore, patients will be enrolled in the study gender-independently.

Who cannot join

  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion protein; Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
  • Any known contraindication (including hypersensitivity) to docetaxel, 5-FU, leucovorin, or oxaliplatin.
  • 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 of following conditions are met:
  • Rash must cover < 10% of body surface area
  • 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
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  • Prior allogeneic bone marrow transplantation or prior solid organ transplantation
  • 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 computed tomography (CT) scan.
  • Note: History of radiation pneumonitis within the radiation field (fibrosis) is permitted.
  • Positive test for human immunodeficiency virus (HIV)
  • Active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test prior to randomization) or hepatitis C 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).
  • Active tuberculosis
  • Known dihydropyrimidine dehydrogenase (DPD) deficiency. Patients with a reduced DPD activity (CPIC activity score of 1.0-1.5) might participate in the study and receive a reduced dosage of 5-FU after discussion with the lead investigator and sponsor
  • Uncontrolled tumor-related pain; Patients requiring pain medication must be on a stable regimen at study entry
  • 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 5 months after the last dose of atezolizumab
  • Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA4, anti-PD-1, or anti-PD-L1 therapeutic antibodies
  • 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
  • Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to study enrollment. The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) is allowed.
  • 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.
  • Clinically significant valvular defect
  • History of other malignancy within 3 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
  • Known central nervous system metastases
  • Peripheral polyneuropathy ≥ NCI CTCAE grade 2
  • Serum albumin < 2.5 g/dL.
  • Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL or corrected serum calcium > ULN)
  • Serious infection requiring oral or IV antibiotics within 14 days prior to study enrollment
  • Chronic inflammatory bowel disease
  • Clinically significant active gastrointestinal bleeding
  • Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment
  • 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
  • Participation in another interventional clinical study ≤ 30 days prior to study enrollment or planned participation in such a study at the same time as this study
  • Receipt of an investigational drug within 28 days prior to initiation of study drug
  • Pregnancy or breast feeding or planning to become pregnant within 5 months after the end of treatment. Women of childbearing potential must have a negative serum pregnancy test result within 7 days prior to enrollment.

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

Germany1 site

  • Krankenhaus Nordwest

    Frankfurt, 60488

Other trials in Germany

Switzerland1 site

  • SAKK Coordinating Center

    Bern, 3008

Other trials in Switzerland

About this study

Official title: A Randomized, Open-label Phase II/III Efficacy and Safety Study of Atezolizumab in Combination With FLOT Versus FLOT Alone in Patients With Gastric Cancer and Adenocarcinoma of the Oesophago-gastric Junction and High Immune Responsiveness (MO30039/MO43340) - The IKF-DANTE Trial

This is a multicenter, randomized, controlled, open-label study comparing perioperative atezolizumab with FLOT chemotherapy versus FLOT alone in patients with locally advanced, operable adenocarcinoma of the stomach or GEJ with high immune responsiveness.

Read the detailed description

The study will evaluate the safety and efficacy of the study treatment regimens. Potential study participants will be assessed for eligibility during a 28-day screening period. Only immune-competent patients with either of the following MSI-high, PD-L1 CPS≥1, TMB ≥10/MB or EBV+ will be enrolled. Eligible patients will be randomized to perioperative treatment with either atezolizumab with FLOT (Arm A) or FLOT alone (Arm B). Randomization will occur in a 1:1 ratio with stratification by clinical nodal stage (N+ vs. N-), location of the primary (GEJ type I vs. GEJ type II/III vs. stomach), and PD-L1-combined positive score (CPS≥5 vs. CPS<5) or MSI-status (MSI/MMRd vs. MSS/MMRp).

Following randomization, study patients will enter the study treatment period which will last approximately 22 to 52 weeks depending on treatment arm and timing of surgery.

Arm A: FLOT with Atezolizumab:

Patients randomized to treatment Arm A will receive atezolizumab + FLOT in four 2-week treatment cycles as described below prior to undergoing surgery. Following surgery, patients will receive another four 2-week cycles of atezolizumab + FLOT followed by 8 additional 3-week treatment cycles with atezolizumab alone.

Arm B: FLOT alone:

Patients randomized to Arm B will receive FLOT alone for four 2-week treatment cycles prior to surgery. Following surgery, patients will receive another four 2-week cycles of chemotherapy alone.

Being tested
Atezolizumab, 5-Fluorouracil, Calciumfolinat, Oxaliplatin, Docetaxel
Medical subject headings
Stomach Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AtezolizumabDrug

    Also called TECENTRIQ

    Day 1 q2w: 840 mg IV over 1 hour (4 cycles perioperative with FLOT) + Day 1 q3w: 1200 mg IV over 1 hour (8 additional cycles monotherapy)

  • 5-FluorouracilDrug

    Also called 5-FU

    Day 1 q2w: 2600 mg/m² IV over 24 hours

  • CalciumfolinatDrug

    Also called Leucovorin

    Day 1 q2w: 200 mg/m² IV over 1 hour

  • OxaliplatinDrug

    Also called ELOXATIN

    Day 1 q2w: 85 mg/m² IV over 2 hours

  • DocetaxelDrug

    Also called TAXOTERE

    Day 1 q2w: 50 mg/m² IV over 1 hour

Study groups in NCT03421288
Study groupRoleWhat they receive
Arm A: FLOT with AtezolizumabExperimentalPatients randomized to treatment Arm A will receive atezolizumab (840 mg IV over 1 hour) + FLOT in four 2-week treatment cycles prior to undergoing surgery. Following surgery, patients will receive another four 2-week cycles of atezolizumab + FLOT followed by 8 additional 3-week treatment cycles with atezolizumab alone (maintenance setting: 1,200 mg q3w). FLOT can be deescalated to FLO, FLT or FL in case of chemorelated toxicity at any time and at the discretion of investigator.
Receives: Drug: Atezolizumab; Drug: 5-Fluorouracil; Drug: Calciumfolinat; Drug: Oxaliplatin; Drug: Docetaxel
Arm B: FLOT aloneActive comparatorPatients randomized to Arm B will receive FLOT alone for four 2-week treatment cycles prior to surgery. Following surgery, patients will receive another four 2-week cycles of chemotherapy alone. FLOT can be deescalated to FLO, FLT or FL in case of chemo-related toxicity at any time and at the discretion of investigator. Docetaxel 50 mg/m², d1 Oxaliplatin 85 mg/m², d1 Calciumfolinat 200 mg/m², d1 5-Fluorouracil 2600 mg/m², d1
Receives: Drug: 5-Fluorouracil; Drug: Calciumfolinat; Drug: Oxaliplatin; Drug: Docetaxel

What is being measured

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

  1. Comparison of Event free survival (EFS) between arms

    to compare Event free survival (EFS) in patients with locally advanced, operable esophagogastric adenocarcinoma receiving perioperative FLOT with atezolizumab versus FLOT alone in the intent to treat population (ITT) and where EFS is defined as the time from randomization to disease progression or relapse after surgery or death from any cause

    Measured: 10 years

Secondary outcomes (5)

  1. Pathological complete regression (pCR, TRG 1a by Becker) rate

    Pathological complete regression (pCR, TRG 1a by Becker) rate where pCR is defined as the absence of residual tumor based on evaluation of the resected esophagogastric specimen in the primary by a central reference pathologist

    Measured: after 4 cycles (each cycle is 14 days) + surgery; i.e. after 12 weeks in total

  2. Pathological complete and subtotal regression (TRG1a/b by Becker)

    Pathological complete and subtotal regression (TRG1a/b by Becker). TRG1a/b is defined as < 10% residual tumor per tumor bed based on evaluation of the resected esophagogastric specimen in the primary by a central reference pathologist.

    Measured: after 4 cycles (each cycle is 14 days) + surgery; i.e. after 12 weeks in total

  3. R0 resection rate

    R0 resection rate where R0 resection is defined as a microscopically margin negative resection with no gross or microscopic tumor remains in the areas of the primary tumor and/or sampled regional lymph nodes based on evaluation by the local pathologist.

    Measured: after 4 cycles (each cycle is 14 days) + surgery; i.e. after 12 weeks in total

  4. Overall survival (OS)

    Overall survival (OS) where OS is defined as the time from randomization to death from any cause

    Measured: 10 years

  5. Overall survival (OS) and EFS in the subgroup of patients with PD-L1 CPS score ≥ 5 and ≥ 10 and patients with MSI

    Overall survival (OS) where OS is defined as the time from randomization to death from any cause and EFS, where EFS is defined as the time from randomization to disease progression or relapse after surgery or death from any cause, both compared between the specific subgroups

    Measured: 10 years

Timeline

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

  1. First posted5 Feb 2018
  2. Study start14 Sep 2018
  3. Primary completion31 May 2027 (estimated)
  4. Study completion31 Dec 2027 (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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
677 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03421288
Sponsor's protocol ID
DANTE/FLOT8
Other IDs
2017-001979-23, MO30039/MO43340, AIO-STO-0317, IKF-s633, 2017
Acronym
DANTE
Status last verified
Jul 2025
First submitted
11 Jan 2018
Last updated
25 Jul 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: No IPD will be shared.

Publications

  • Lorenzen S, Gotze TO, Thuss-Patience P, Biebl M, Homann N, Schenk M, Lindig U, Heuer V, Kretzschmar A, Goekkurt E, Haag GM, Riera-Knorrenschild J, Bolling C, Hofheinz RD, Zhan T, Angermeier S, Ettrich TJ, Siebenhuener AR, Elshafei M, Bechstein WO, Gaiser T, Loose M, Sookthai D, Kopp C, Pauligk C, Al-Batran SE; AIO and SAKK Study Working Groups. Perioperative Atezolizumab Plus Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel for Resectable Esophagogastric Cancer: Interim Results From the Randomized, Multicenter, Phase II/III DANTE/IKF-s633 Trial. J Clin Oncol. 2024 Feb 1;42(4):410-420. doi: 10.1200/JCO.23.00975. Epub 2023 Nov 14.

    PubMed 37963317

  • Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore). 2022 May 27;101(21):e29304. doi: 10.1097/MD.0000000000029304.

    PubMed 35623069

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Atezolizumab, 5-Fluorouracil and Calciumfolinat in people with Gastric Cancer and Gastroesophageal Junction Adenocarcinoma, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 2 sites in 2 countries.

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 22 inclusion and 33 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 25 Jul 2025. 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, Switzerland. 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?

Comparison of Event free survival (EFS) between arms (time frame: 10 years). 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 NCT03421288, which also lists 2 linked publications.

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 25 Jul 2025.

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