| Eligibility |
Inclusion Criteria:
1. Histologically proven, gastric or GEJ adenocarcinoma (Siewert I-III).
2. Availability of a paraffin block from the diagnostic endoscopic biopsy (and a fresh
biopsy if possible), and a second tumor block (fresh + paraffin) from the surgical
specimen.
3. Have evaluable disease as defined by RECIST 1.1 and determined by investigator
assessment, with the absence of distant metastases on CT scan of thorax, abdomen and
pelvis.
4. Patient medically fit and amenable to gastrectomy/esophagectomy with curative intent
as confirmed by a multidisciplinary team discussion.
5. UICC tumor stage Ib (T1N1 only, T2N0 not eligible) to IIIC, as defined by CT,
according to the 7th AJCC Edition.
6. Age = 18 years.
7. WHO performance status 0-1.
8. Adequate organ function (assessed within 7 days prior treatment initiation):
1. White blood cell count (WBC) > 3 x 109 /L
2. Absolute neutrophil count (ANC) > 1.5 x 109 /L
3. Platelets = 100 x 109 /L
4. Estimated glomerular filtration rate should be > 50 ml/min
5. Total bilirubin within normal limits (if the patient has documented Gilbert's
disease = 1.5 x ULN or direct bilirubin = ULN).
6. Aspartate transaminase (AST) and alanine transaminase (ALT) = 2.5 x ULN.
9. In case of anticoagulation, investigator and patient should agree to replace any oral
anticoagulation by subcutaneous administration of low-molecular weight heparin in
equivalent doses before treatment start;
10. For women who are not postmenopausal (> 12 months of non-therapy induced amenorrhea)
or surgically sterile (absence of ovaries and/or uterus): agreement to remain
abstinent or use single or combined contraceptive methods that result in a failure
rate of < 1% per year during the treatment period and for at least 12 months after the
last treatment dose.
11. For men: agreement to 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 12 months after the last dose of study
treatment. Abstinence is only acceptable if it is in line with the preferred and usual
lifestyle of the patient. Periodic abstinence (e.g. calendar, ovulation,
symptothermal, or postovulation methods) and withdrawal are not acceptable methods for
contraception.
12. For all female patients who are not confirmed postmenopausal (> 12 months of
non-therapy induced amenorrhea) or surgically sterile (absence of ovaries and/or
uterus) a negative serum pregnancy test (ß-human chorionic gonadotropin [ß-hCG])
result should be available before treatment and within 7 days from treatment start
should be performed. Female patients should not be breast feeding.
13. Written informed consent must be given according to ICH/GCP, and national/local
regulations.
Exclusion Criteria:
1. Other histology different from adenocarcinoma.
2. Has had previous therapy for gastric or GEJ cancer.
3. Known hypersensitivity to the components of anti-PD-L1, docetaxel, oxaliplatin,
fluorouracil/leucovorin.
4. Known dihydropyrimidine dehydrogenase (DPD) deficiency.
5. Previous malignancy within the last 5 years, except for adequately treated cervical
carcinoma in situ, localized non-melanoma skin cancer, or other curatively treated
cancer without impact on the patient's overall prognosis according to the judgment of
the investigator.
6. Any psychological, familial, sociological or geographical condition potentially
hampering compliance with the study protocol and follow-up schedule; those condition
should be discussed with the patient before registration in the trial.
7. History of clinically significant comorbidities.
8. Patients medically unfit for FLOT chemotherapy, according to the local guidance.
9. Active autoimmune disease that has required systemic treatment in past 2 years (i.e.
with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
Replacement therapy (e.g., thyroxin, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.
10. Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other
form of immunosuppressive therapy within 7 days prior to the first dose of trial
treatment. Current use of immunosuppressive medication, EXCEPT for the following: a.
intranasal, inhaled, topical steroids, or local steroid injection (e.g.,
intra-articular injection); b. Systemic corticosteroids at physiologic doses = 10
mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity
reactions (e.g., CT scan premedication). History or evidence of interstitial lung
disease or active, non-infectious pneumonitis.
11. Active infection requiring systemic therapy.
12. Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies) or Active
Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is
detected). Test for HBV and HCV are required for the screening.
13. Received a live vaccine within 30 days of planned start of study therapy. Note:
Seasonal influenza vaccines for injection are generally inactivated flu-vaccines and
are allowed; however intranasal influenza vaccines are live attenuated vaccines, and
are not allowed.
14. Prior organ transplantation including allogenic stem-cell transplantation.
15. Known prior severe hypersensitivity to investigational product or any component in its
formulations, including known severe hypersensitivity reactions to monoclonal
antibodies (NCI-CTCAE v4.0 Grade = 3).
16. Persisting toxicity related to prior therapy (NCI-CTCAE v4.0 Grade > 1); however,
alopecia, sensory neuropathy Grade = 2, or other Grade = 2 not constituting a safety
risk based on investigator's judgment are acceptable.
17. Other severe acute or chronic medical conditions including immune colitis,
inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric
conditions including recent (within the past year) or active suicidal ideation or
behaviour; or laboratory abnormalities that may increase the risk associated with
study participation or study treatment administration or may interfere with the
interpretation of study results and, in the judgment of the investigator, would make
the patient inappropriate for entry into this study.
18. Pregnant women and lactating females are excluded from this study
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