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SNCTP000003615 | NCT03421288 | BASEC2019-01150

Eine randomisierte, offene Phase-II-Studie zur Wirksamkeit und Sicherheit von Atezolizumab in Kombination mit FLOT versus FLOT allein bei Patienten mit Magenkrebs und Adenokarzinom des ösophagogastralen Übergangs – Die DANTE Studie

Data source: BASEC (Imported from 25.09.2020), WHO (Imported from 20.09.2020)
Changed: 17.06.2020
Disease category: Other Cancer

Brief description of trial (Data source: BASEC)

Die DANTE Studie ist eine multizentrische, multinationale Studie (Deutschland, Schweiz). Sie untersucht die die Wirksamkeit und Verträglichkeit der Studienmedikation (Studienarm A) Atezolizumab in Kombination mit FLOT (bestehend aus den Medikamenten 5-Fluorouracil (5-FU), Folinsäure, Oxaliplatin und Docetaxel) zur Vor- und Nachbehandlung des Magentumors oder des Tumors der unteren Speiseröhre.

Verglichen wird diese neue Kombination mit der Standardtherapie (Studienarm B) FLOT vor, während und nach der Operation. Patienten werden 1:1 randomisiert, das heisst, Sie haben eine 50% Wahrscheinlichkeit in den Studienarm A oder 50% in den Studienarm B zu kommen.

Wir machen diese Studie, um zu prüfen, ob durch die Hinzunahme des Antikörpers Atezolizumab, die Zeit bis zum Fortschreiten oder Wiederauftreten des Tumors verlängert werden kann oder ob es auch langfristig bei mehr Patienten zu gar keinem Rückfall mehr kommt.

Health conditions investigated (Data source: BASEC)

bösartiger Tumor (Adenokarzinom) des Magens oder der unteren Speiseröhre

Health conditions (Data source: WHO)

Gastric Cancer;Gastroesophageal Junction Adenocarcinoma

Rare disease (Data source: BASEC)

No

Intervention investigated (e.g. drug, therapy or campaign) (Data source: BASEC)

Arm B
Standardbehandlung: 4 Zyklen FLOT vor der Operation und 4 Zyklen nach der Operation.

Arm A
Standardbehandlung mit 4 Zyklen FLOT sowie jeweils 4 Verabreichungen des Antikörpers Atezolizumab. Auch diese Therapie wird nach der Operation wiederholt. Nach Ende der FLOT-Therapie erhalten Sie in dieser Gruppe noch weitere 8 Dosen Atezolizumab, dann aber alle drei Wochen.

Die Studienteilnehmer werden nach Ende der Studientherapie je nach Verlauf der Erkrankung bis zu fünf Jahre nachkontrolliert.

Interventions (Data source: WHO)

Drug: Atezolizumab;Drug: 5-Fluorouracil;Drug: Calciumfolinat;Drug: Oxaliplatin;Drug: Docetaxel

Criteria for participation in trial (Data source: BASEC)

- Schriftliche Einwilligungserklärung vorhanden
- Ist gemäss Prüfarzt bereit und in der Lage die Vorgaben des Studienprotokolls einzuhalten, einschliesslich der geplanten chirurgischen Behandlung
- Weibliche und männliche Patienten ≥ 18 Jahre alt

Exclusion criteria (Data source: BASEC)

- Vorgeschichte von schweren allergischen, anaphylaktischen oder anderen überempfindlichen Reaktionen auf chimäre oder humanisierte Antikörper oder Fusionsproteine; bekannte Überempfindlichkeit gegenüber chinesischen Hamster-Eierstockzellprodukten oder gegenüber jeglicher Komponente der Atezolizumab-Rezeptur
- Jede bekannte Kontraindikation (einschließlich Überempfindlichkeit) gegenüber Docetaxel, 5-FU, Leucovorin oder Oxaliplatin
- Vorherige allogene Knochenmarktransplantation oder vorhergehende Organ-Transplantation

Inclusion/Exclusion Criteria (Data source: WHO)


Inclusion Criteria:

1. Have provided written informed consent

2. In the investigator's judgement, is willing and able to comply with the study protocol
including the planned surgical treatment

3. Female and male patients* = 18 years of age

4. 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:

1. is not infiltrating any adjacent organs or structures by CT or MRI evaluation

2. does not involve peritoneal carcinomatosis

3. 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 or upon request of the central review.

5. No prior cytotoxic or targeted therapy

6. No prior partial or complete esophagogastric tumor resection

7. ECOG = 1

8. 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). 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.

9. 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 tubal ligation,
male sterilization, hormonal implants, established, proper use of combined oral or
injected hormonal contraceptives, and certain intrauterine devices. Alternatively, two
methods (e.g., two barrier methods such as a condom and a cervical cap) may be
combined to achieve a failure rate of < 1% per year. Barrier methods must always be
supplemented with the use of a spermicide. 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.

10. Males must agree to remain abstinent (refrain from heterosexual intercourse) or use
contraceptive measures, and agree to refrain from donating sperm, as defined below:

a. 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.

11. Adequate hematological, hepatic and renal function as indicated by the following
parameters:

- Leukocytes = 3.000/mm³, platelets = 100.000/mm3 without transfusion, absolute
neutrophil count (ANC) = 1500/mm3 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, 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.

Exclusion Criteria:

1. 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

2. Any known contraindication (including hypersensitivity) to docetaxel, 5-FU,
leucovorin, or oxaliplatin.

3. 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

4. Prior allogeneic bone marrow transplantation or prior solid organ transplantation

5.

Further information on the trial in WHO primary registry

https://clinicaltrials.gov/show/NCT03421288

Further information on the trial from WHO database (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT03421288

Further information on trial

Date trial registered

11.01.2018

Incorporation of the first participant

14.09.2018

Recruitment status

Recruiting

Academic title (Data source: WHO)

A Randomized, Open-label Phase II 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 (MO30039) - The DANTE Trial

Type of trial (Data source: WHO)

Interventional

Design of the trial (Data source: WHO)

Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).

Phase (Data source: WHO)

Phase 2

Primary end point (Data source: WHO)

Comparison of DFS/PFS between arms

Secundary end point (Data source: WHO)

immune cell infiltration rate;Overall survival (OS);R0 resection rate;TRG1a and TRG1a/b in the sampled regional lymph nodes;Pathological complete and subtotal regression (TRG1a/b by Becker);Pathological complete regression (pCR, TRG 1a by Becker) rate

Contact information (Data source: WHO)

Please refer to primary and secondary sponsors

Trial results (Data source: WHO)

Results summary

no information available yet

Link to the results in the primary register

no information available yet

Information on the availability of individual participant data

no information available yet

Trial sites

Trial sites in Switzerland (Data source: BASEC)

Aarau, Baden, Basel, Bern, Chur, Geneva, Martigny, Olten, Rapperswil, Sierre, Sion, Winterthur, Zurich

Countries (Data source: WHO)

Germany, Switzerland

Contact for further information on the trial

Details of contact in Switzerland (Data source: BASEC)

SAKK, Daniela Bärtschi
+41 31 389 91 91
trials@sakk.ch

Contact for general information (Data source: WHO)

Salah-Eddin Al-Batran, Prof.
IKF Institute of Clinical Cancer Research at Krankenhaus Nordwest
069 7601 4420
albatran.salah@khnw.de

Contact for scientific information (Data source: WHO)

Salah-Eddin Al-Batran, Prof.
IKF Institute of Clinical Cancer Research at Krankenhaus Nordwest
069 7601 4420
albatran.salah@khnw.de

Principal Sponsor/Investigator

Principal sponsor (Data source: WHO)

IKF Klinische Krebsforschung GmbH at Krankenhaus Nordwest

Authorisation by the ethics committee (Data source: BASEC)

Name of the authorising ethics committee (for multicentre studies only the lead committee)

Kantonale Ethikkommission Zürich

Date of authorisation by the ethics committee

19.12.2019

Further trial identification numbers

Trial identification number of the ethics committee (BASEC-ID) (Data source: BASEC)

2019-01150

Secondary ID (Data source: WHO)

2017-001979-23
MO30039
AIO-STO-0317
DANTE/FLOT8