DANTE FLOT8 - A randomized, open-label Phase II/III study of the efficacy and safety of Atezolizumab in combination with FLOT versus FLOT alone in patients with gastric cancer and adenocarcinoma of the esophagogastric junction and high immune reactivity (MO30039/MO43340) – The DANTE study

Germany, Switzerland (ICTRP)

ICTRP Trial ID
NCT03421288 (ICTRP)

Official title (approved by ethics committee)
DANTE 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 oe-sophago-gastric junction and high immune responsiveness (MO30039/MO43340) – The IKF-DANTE Trial (BASEC)

Academic 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 DANTE Trial (ICTRP)

Public title
Study of Atezolizumab + FLOT vs. FLOT Alone in Patients With GC/GEJ and High Immune Responsiveness (ICTRP)

Disease under investigation
Gastric Cancer;Gastroesophageal Junction Adenocarcinoma (ICTRP)

Intervention under investigation
Drug: Atezolizumab;Drug: 5-Fluorouracil;Drug: Calciumfolinat;Drug: Oxaliplatin;Drug: Docetaxel (ICTRP)

Type of trial
Interventional (ICTRP)

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

Inclusion/Exclusion criteria
Gender: All
Maximum age: N/A
Minimum age: 18 Years

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. 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). 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).

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 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:

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.

10. Criterion integrated in criterion 9.

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

- Leukocytes = 3.000/mm?, 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.

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, Sj?gren's syndrome, Guillain-Barr? 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 mo (ICTRP)

not available

Primary and secondary end points
Comparison of Event free survival (EFS) between arms (ICTRP)

Pathological complete regression (pCR, TRG 1a by Becker) rate;Pathological complete and subtotal regression (TRG1a/b by Becker);R0 resection rate;Overall survival (OS);Overall survival (OS) and EFS in the subgroup of patients with PD-L1 CPS score = 5 and = 10 and patients with MSI (ICTRP)

Registration date
not available

Incorporation of the first participant
not available

Secondary sponsors
Roche Pharma AG (ICTRP)

Additional contacts
Salah-Eddin Al-Batran, Prof.;Thorsten Goetze, Prof.;Thorsten Goetze, Prof., goetze.thorsten@khnw.de, 069 7601 4420, Institute of Clinical Cancer Research IKF at Krankenhaus Nordwest,University Cancer Center Frankfurt, Krankenhaus Nordwest, (ICTRP)

Secondary trial IDs
2017-001979-23, MO30039/MO43340, AIO-STO-0317, IKF-s633, DANTE/FLOT8 (ICTRP)

Results-Individual Participant Data (IPD)
not available

Further information on the trial
https://clinicaltrials.gov/ct2/show/NCT03421288 (ICTRP)