Combining chemotherapy with HIPEC for gastric cancer treatment

Preventive HIPEC in Combination With Perioperative FLOT Versus FLOT Alone for Resectable Diffuse Type Gastric and Gastroesophageal Junction Type II/III Adenocarcinoma - The Phase III "PREVENT" Trial of the AIO /CAOGI /ACO

This study tests if adding a special heated chemotherapy treatment during surgery can help people with certain types of stomach cancer do better than just using chemotherapy alone.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 200 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Krankenhaus Nordwest (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 15 sites (Aachen and 14 other locations)
• Trial ID: NCT04447352 on ClinicalTrials.gov

What this trial studies

This multicenter, randomized, controlled, open-label study evaluates the efficacy and safety of perioperative FLOT chemotherapy combined with intraoperative HIPEC compared to FLOT chemotherapy alone in patients with resectable localized and locally advanced diffuse and mixed type adenocarcinoma of the stomach and gastroesophageal junction. Patients will receive 3-6 cycles of neoadjuvant FLOT chemotherapy before undergoing the HIPEC procedure. The trial aims to assess both the effectiveness and tolerability of this combined treatment approach.

Who should consider this trial

Good fit: Ideal candidates are patients aged 18 to 75 with resectable diffuse or mixed type adenocarcinoma of the stomach or gastroesophageal junction who have received neoadjuvant FLOT chemotherapy.

Not a fit: Patients with distant metastases or those who have undergone prior tumor resection may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes for patients with gastric cancer and gastroesophageal junction adenocarcinoma.

How similar studies have performed: Other studies have shown promising results with similar approaches, indicating potential for success in this trial.

Eligibility criteria

Inclusion Criteria:

1. Histologically confirmed, medically operable, resectable diffuse or mixed type (according to Lauren's classification) adenocarcinoma of the gastroesophageal junction (AEG II-III) or the stomach (uT3, uT4a, any N category, M0), or any T N+ M0 patient
2. Patient has received 3 to 6 cycles of neoadjuvant FLOT (de-escalation or dose modification allowed)
3. No preceding cytotoxic or targeted therapy other than neoadjuvant FLOT (including de-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 childbearing potential needs to have a negative pregnancy test within 7 days prior to study start. Males and females of reproductive potential must agree to practice highly effective contraceptive measures\* during the study. Male patients must also agree to refrain from father a child during treatment and additionally to use a condom during treatment period. Their female partner of childbearing potential must also agree to use an adequate contraceptive measure.

   \*highly effective (i.e. failure rate of \<1% per year when used consistently and correctly) methods: intravaginal and transdermal combined (estrogen and progestogen containing) hormonal contraception; injectable and implantable progestogen-only hormonal contraception; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomised partner; sexual abstinence (complete abstinence is defined as refraining from heterosexual intercourse during the 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, bone scan or MRI (if bone metastases are suspected due to clinical signs). Exclusion of the infiltration of any adjacent organs or structures by CT or MRI
8. Laparoscopic exclusion of peritoneal carcinomatosis at initial staging, before start of FLOT chemotherapy
9. Hematological, hepatic and renal function parameters adequate to allow surgical procedure and HIPEC at investigator´s discretion
10. Patient able and willing to provide written informed consent and to comply with the study protocol and with the planned surgical procedures

Exclusion Criteria:

1. Patient without neoadjuvant therapy or those who received a neoadjuvant therapy other 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 congestive heart failure, NYHA III-IV
5. Clinically significant valvular defect
6. Past or current history of other malignancies not curatively treated and without evidence of disease for more than 3 years, except for curatively treated basal cell carcinoma 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 invasion of adjacent organs (T4b).
   * Patients with involved retroperitoneal (e.g. para-aortal, paracaval or interaortocaval 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 a history of hepatic encephalopathy or ascites.
11. On-treatment participation in another interventional clinical study in the period 30 days 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

Where this trial is running

Aachen and 14 other locations

• Uniklinik RWTH Aachen, AöR, Medizinische Klinik III, Studienzentrum Viszeralmedizin — Aachen, Germany (Recruiting)
• Universitätsklinikum, Klinik und Poliklinik für Viszeral-, Thorax- und Gefäßchirurgie — Dresden, Germany (Recruiting)
• Institute of Clinical Cancer Research (IKF), UCT - University Cancer Center, Frankfurt, Germany — Frankfurt, Germany (Recruiting)
• Universitätsklinikum Halle (Saale), Universitätsklinik und Poliklinik für Viszerale, Gefäß- und Endokrine Chirurgie — Halle, Germany (Recruiting)
• Universitätsklinikum Leipzig, Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie — Leipzig, Germany (Recruiting)
• Klinikum Ludwigsburg, Klinik für Innere Medizin, Gastroenterologie, Hämato-Onkologie, Pneumologie, Diabetologie und Infektiologie — Ludwigsburg, Germany (Recruiting)
• Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Klinik für Chirurgie — Lübeck, Germany (Recruiting)
• Universitätsklinikum Magdeburg — Magdeburg, Germany (Recruiting)
• Klinikum rechts der Isar der TU München, Klinik und Poliklinik für Innere Medizin III — München, Germany (Recruiting)
• Universitätsklinikum Münster, Klinik für Allgemein-, Viszeral- und Transplantationschirurgie — Münster, Germany (Recruiting)
• Krankenhaus Barmherzige Brüder Regensburg, Klinik für Onkologie und Hämatologie — Regensburg, Germany (Recruiting)
• Klinikum Südstadt Rostock, Klinik für Innere Medizin III — Rostock, Germany (Recruiting)
• Universitätsklinikum Tübingen, Universitätsklinik für Allgemeine, Viszeral- und Transplantationschirurgie Chirurgische Studienzentrale — Tübingen, Germany (Recruiting)
• Marien-Hospital Witten — Witten, Germany (Recruiting)
• Universitätsklinikum Würzburg, Chirurgische Klinik I, Chirurgisches Studienzentrum — Würzburg, Germany (Recruiting)

Study contacts

• Principal investigator: Thorsten O Götze, MD — Lead Coordinating Investigator
• Study coordinator: Thorsten O Götze, MD

Conditions Gastric Cancer; Gastroesophageal Junction Adenocarcinoma