HIPEC + FLOT vs. FLOT Alone in Patients With Gastric Cancer and GEJ (PREVENT)

Inclusion Criteria:

1. Histologically confirmed, medically operable, resectable diffuse or mixed type (according to Lauren's classification) adenocarcinoma of the gastroesophagealjunction (AEG II-III) or the stomach (uT3, uT4a, any N category, M0), or any T N+ M0patient

2. Patient has received 3 to 6 cycles of neoadjuvant FLOT (de-escalation or dosemodification allowed)

3. No preceding cytotoxic or targeted therapy other than neoadjuvant FLOT (includingde-escalated or dose reduced schema) therapy

4. No prior partial or complete tumor resection

5. Female and male patient ≥ 18 and ≤ 75 years. Female patient with childbearingpotential needs to have a negative pregnancy test within 7 days prior to studystart. Males and females of reproductive potential must agree to practice highlyeffective contraceptive measures* during the study. Male patients must also agree torefrain from father a child during treatment and additionally to use a condom duringtreatment period. Their female partner of childbearing potential must also agree touse an adequate contraceptive measure.

*highly effective (i.e. failure rate of <1% per year when used consistently andcorrectly) methods: intravaginal and transdermal combined (estrogen and progestogencontaining) hormonal contraception; injectable and implantable progestogen-onlyhormonal contraception; intrauterine device (IUD); intrauterine hormone-releasingsystem (IUS); bilateral tubal occlusion; vasectomised partner; sexual abstinence (complete abstinence is defined as refraining from heterosexual intercourse duringthe entire period of risk associated with the study treatments).

6. ECOG ≤ 1

7. Exclusion of distant metastases by CT or MRI of abdomen, pelvis, and thorax, bonescan or MRI (if bone metastases are suspected due to clinical signs). Exclusion ofthe infiltration of any adjacent organs or structures by CT or MRI

8. Laparoscopic exclusion of peritoneal carcinomatosis at initial staging, before startof FLOT chemotherapy

9. Hematological, hepatic and renal function parameters adequate to allow surgicalprocedure and HIPEC at investigator´s discretion

10. Patient able and willing to provide written informed consent and to comply with thestudy protocol and with the planned surgical procedures

Exclusion Criteria:

1. Patient without neoadjuvant therapy or those who received a neoadjuvant therapyother than FLOT

2. Known hypersensitivity against 5-FU, leucovorin, oxaliplatin, or docetaxel

3. Other known contraindications against, 5-FU, leucovorin, oxaliplatin, or docetaxel

4. Clinically significant active coronary heart disease, cardiomyopathy or congestiveheart failure, NYHA III-IV

5. Clinically significant valvular defect

6. Past or current history of other malignancies not curatively treated and withoutevidence of disease for more than 3 years, except for curatively treated basal cellcarcinoma of the skin and in situ carcinoma of the cervix

7. Criteria of primary unresectability, e.g.:

• Radiologically documented evidence of major blood vessel invasion or invasionof adjacent organs (T4b).

• Patients with involved retroperitoneal (e.g. para-aortal, paracaval orinteraortocaval lymph nodes) or mesenterial lymph nodes (distant metastases!)

8. Other severe internal disease or acute infection

9. Patient has undergone major surgery within 28 days prior to enrollment

10. Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and ahistory of hepatic encephalopathy or ascites.

11. On-treatment participation in another interventional clinical study in the period 30days prior to inclusion and during the study

12. Patient pregnant or breast feeding, or planning to become pregnant

13. Patient in a closed institution according to an authority or court decision (AMG § 40, Abs. 1 No. 4)

14. Any other concurrent antineoplastic treatment including irradiation

15. Known intraabdominal adhesion situs

16. Pre-existing peritoneal seeding