A Study of Total Neoadjuvant Chemotherapy With FLOT VS Standard Perioperative FLOT in Patients With Gastric or GEJ Cancer

Inclusion Criteria:

1. Must provide written informed consent.

2. Must be ≥18 years of age.

3. Must have life expectancy of greater than 3 months.

4. Must have pathologically proven Siewert type II or III GEJ or gastric adenocarcinomafrom the main tumor or local lymph nodes (pre-neoadjuvant chemo).

5. Stage cT2 or higher, any N and M0, are eligible for the study.

6. M0 disease must be established by both negative distant metastatic disease onimaging AND negative diagnostic laparoscopic assisted cytology of peritoneal fluidcytology not more than 42 days before registration.

7. Must be a candidate for neoadjuvant chemotherapy.

8. Must be a candidate for curative surgical approach.

9. Must have an ECOG performance status 0-2.

10. Male or female subjects of childbearing potential must be willing to usecontraceptive precautions throughout the trial and for 3 months afterdiscontinuation of study treatment. Female subjects of childbearing potential musthave a negative pregnancy test within 28 days of registration. Post-menopausal womenmust be amenorrhoeic for at least 12 months to be considered of non-childbearingpotential.

11. Must have adequate kidney, liver, and bone marrow function, within 28 days prior toregistration, as follows:

i. Hemoglobin ≥ 8.0 gm/dL (PRBC transfusion is allowed to meet this criteria) ii. Absolute neutrophil count (ANC) ≥ 1000 cells/mm3 iii. Platelet count ≥ 100,000 /mm3 iv. Total bilirubin ≤ 1.5 times upper limit of normal (ULN) v. AST (SGOT) and ALT (SGPT) ≤ 3.0 times the ULN vi. Patient must have adequate renal function as evidenced by one of the following: Serum creatinine ≤ IULN OR calculated creatinine clearance ≥ 60 mL/min. This serum creatinine result must be obtained within 28 days prior to registration.

l. Subjects who have required a short course urgent single modality non curative radiation treatment or gastric artery embolization for the purpose of tumor bleeding control are eligible.

Exclusion Criteria:

1. Positive cytology or histology for metastatic disease on diagnostic laparoscopyperitoneal fluid. Reports such as: "cannot rule out malignancy" or "suspicious formalignancy, but not definitive" will exclude the subject from enrolling.

2. Seiwert type I GEJ cancer

3. Subjects with clinical evidence of metastatic disease.

4. Biopsy proven metastatic disease (excluding regional lymph nodes)

5. Prior chemotherapy for gastric cancer or GEJ cancer

6. No other prior malignancy is allowed except for the following: adequately treatedbasal cell or squamous cell skin cancer, current non-advanced prostate cancer perthe discretion of the investigator, and any other cancers from which the patient hasbeen disease free for two years.

7. Female subjects who are pregnant, breast feeding, or of childbearing potential witha positive pregnancy test prior to baseline. Women of childbearing potential musthave a negative serum pregnancy test as a part of eligibility within 28 days ofregistration. A persistent positive or elevated urine or blood Beta HCG test may becontributed to the primary diagnosis of GC or GEJ cancer after ruling out ectopicand intrauterine pregnancy and germ cell tumors.

8. Subjects unwilling or unable to comply with the protocol or provide written informedconsent.

9. Any medical condition that, in the opinion of the investigator, would exclude thesubject from participating in this study and treatment plan.

10. ECOG > 2