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

NCT04447352 | Recruiting Phase 3 DMC

• 2 other identifiers: HIPEC/FLOT9AIO-STO-0319/ass
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 15

Brief Summary

This is a multicenter, randomized, controlled, open-label study evaluating efficacy and safety of perioperative FLOT chemotherapy plus intraoperative HIPEC versus FLOT chemotherapy alone in patients with resectable localized and locally advanced diffuse and mixed type adenocarcinoma of the stomach and Type II/III GEJ.

Conditions

Gastric Cancer; Gastroesophageal Junction Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Comparison of progression-/disease-free survival (PFS/DFS) between arms

  To compare PFS/DFS in patients with localized and advanced diffuse or mixed type adenocarcinoma of the stomach and Type II/III GEJ (i.e. ≥cT3 any N or any T N-positive) with exclusion of distant metastases and after receiving neoadjuvant FLOT- therapy will be included in this trial after a central review, receiving 3-6 cycles perioperative FLOT versus FLOT alone in the intent to treat population (ITT) and where PFS/DFS is defined as the time from randomization to disease progression or relapse after surgery or death from any cause.

  from randomization up to 5 years

Secondary Outcomes (10)

• Comparison of Overall survival (OS) in both arms

  from randomization up to 5 years

• Comparison of Overall survival rates at 3 and 5 years in both arms

  3 and 5 years after randomization

• Comparison of peritoneal relapse rate at 2 and 3 years in both arms

  2 and 3 years after surgery

• PFS/DFS rates at 2, 3 & 5 years

  2, 3 & 5 years after randomization

• Rate of surgical serious adverse events (SAEs)

  After randomization of the patient until 30 days after last study-specific treatment

Study Arms (2)

Arm A - FLOT

ACTIVE COMPARATOR

Patients randomized to treatment Arm A already received 3-6 cycles of FLOT in 2-week treatment cycles prior to undergoing surgery. Following surgery, patients will receive four further 2-week cycles FLOT. FLOT can be deescalated to FLO, FLT or FL in case of chemorelated toxicity at any time and at the discretion of investigator. FLOT = Docetaxel 50 mg/m², Oxaliplatin 85 mg/m², Leucovorin 200 mg/m², 5-FU 2600 mg/m².

Drug: 5-Fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Docetaxel

Arm B - FLOT/HIPEC

EXPERIMENTAL

Patients randomized to treatment Arm B already received 3-6 cycles of FLOT in 2-week treatment cycles prior to undergoing surgery including Intraoperative Hyperthermic IntraPEritoneal Chemoperfusion (HIPEC) during gastric-/ esophagogastric resection using Cisplatin 75mg/m². Following surgery, patients will receive four further 2-week cycles FLOT. FLOT can be deescalated to FLO, FLT or FL in case of chemorelated toxicity at any time and at the discretion of investigator. FLOT = Docetaxel 50 mg/m², Oxaliplatin 85 mg/m², Leucovorin 200 mg/m², 5-FU 2600 mg/m².

Drug: 5-Fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Docetaxel; Drug: Cisplatin

Interventions

5-Fluorouracil DRUG

Day 1 q2w: 2600 mg/m² IV over 24 hours

Also known as: 5-FU

Arm A - FLOT; Arm B - FLOT/HIPEC

Leucovorin DRUG

Day 1 q2w: 200 mg/m² IV over 30 minutes

Also known as: Calciumfolinat

Arm A - FLOT; Arm B - FLOT/HIPEC

Oxaliplatin DRUG

Day 1 q2w: 85 mg/m² IV over 2 hours

Arm A - FLOT; Arm B - FLOT/HIPEC

Docetaxel DRUG

Day 1 q2w: 50 mg/m² IV over 1 hour

Arm A - FLOT; Arm B - FLOT/HIPEC

Cisplatin DRUG

intraoperative: 75mg/m² intraabdominal solution over 1 hour and 30 minutes

Arm B - FLOT/HIPEC

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Patient has received 3 to 6 cycles of neoadjuvant FLOT (de-escalation or dose modification allowed)
• No preceding cytotoxic or targeted therapy other than neoadjuvant FLOT (including de-escalated or dose reduced schema) therapy
• No prior partial or complete tumor resection
• 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).
• ECOG ≤ 1
• Hematological, hepatic and renal function parameters adequate to allow surgical procedure and HIPEC at investigator´s discretion
• Patient able and willing to provide written informed consent and to comply with the study protocol and with the planned surgical procedures

You may not qualify if:

• Patient without neoadjuvant therapy or those who received a neoadjuvant therapy other than FLOT
• Known hypersensitivity against 5-FU, leucovorin, oxaliplatin, or docetaxel
• Other known contraindications against, 5-FU, leucovorin, oxaliplatin, or docetaxel
• Clinically significant active coronary heart disease, cardiomyopathy or congestive heart failure, NYHA III-IV
• Clinically significant valvular defect
• 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
• 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!)
• Other severe internal disease or acute infection
• Patient has undergone major surgery within 28 days prior to enrollment
• Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a history of hepatic encephalopathy or ascites.
• Patient pregnant or breast feeding, or planning to become pregnant
• Patient in a closed institution according to an authority or court decision (AMG § 40, Abs. 1 No. 4)
• Any other concurrent antineoplastic treatment including irradiation

Sponsors & Collaborators

• Krankenhaus Nordwest: lead
• Deutsche Krebshilfe e.V., Bonn (Germany): collaborator

Study Sites (15)

Uniklinik RWTH Aachen, AöR, Medizinische Klinik III, Studienzentrum Viszeralmedizin

Aachen, 52074, Germany

RECRUITING

Universitätsklinikum, Klinik und Poliklinik für Viszeral-, Thorax- und Gefäßchirurgie

Dresden, 01307, Germany

RECRUITING

Institute of Clinical Cancer Research (IKF), UCT - University Cancer Center, Frankfurt, Germany

Frankfurt, 60488, Germany

RECRUITING

Universitätsklinikum Halle (Saale), Universitätsklinik und Poliklinik für Viszerale, Gefäß- und Endokrine Chirurgie

Halle, 06120, Germany

RECRUITING

Universitätsklinikum Leipzig, Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie

Leipzig, 04103, Germany

RECRUITING

Klinikum Ludwigsburg, Klinik für Innere Medizin, Gastroenterologie, Hämato-Onkologie, Pneumologie, Diabetologie und Infektiologie

Ludwigsburg, 71640, Germany

RECRUITING

Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Klinik für Chirurgie

Lübeck, 23538, Germany

RECRUITING

Universitätsklinikum Magdeburg

Magdeburg, 39120, Germany

RECRUITING

Klinikum rechts der Isar der TU München, Klinik und Poliklinik für Innere Medizin III

München, 81675, Germany

RECRUITING

Universitätsklinikum Münster, Klinik für Allgemein-, Viszeral- und Transplantationschirurgie

Münster, 48149, Germany

RECRUITING

Krankenhaus Barmherzige Brüder Regensburg, Klinik für Onkologie und Hämatologie

Regensburg, 93049, Germany

RECRUITING

Klinikum Südstadt Rostock, Klinik für Innere Medizin III

Rostock, 18059, Germany

RECRUITING

Universitätsklinikum Tübingen, Universitätsklinik für Allgemeine, Viszeral- und Transplantationschirurgie Chirurgische Studienzentrale

Tübingen, 72076, Germany

RECRUITING

Marien-Hospital Witten

Witten, 58452, Germany

RECRUITING

Universitätsklinikum Würzburg, Chirurgische Klinik I, Chirurgisches Studienzentrum

Würzburg, 97080, Germany

RECRUITING

Related Publications (1)

• Gotze TO, Piso P, Lorenzen S, Bankstahl US, Pauligk C, Elshafei M, Amato G, Reim D, Bechstein WO, Konigsrainer A, Monig SP, Rau B, Schwarzbach M, Al-Batran SE. 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"- (FLOT9) trial of the AIO /CAOGI /ACO. BMC Cancer. 2021 Oct 29;21(1):1158. doi: 10.1186/s12885-021-08872-8.

  PMID: 34715810 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Fluorouracil; Leucovorin; Oxaliplatin; Docetaxel; Cisplatin

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Thorsten O Götze, MD

  Lead Coordinating Investigator

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Thorsten O Götze, MD

CONTACT

+4969 7601; goetze.thorsten@khnw.de

Claudia Pauligk, PhD

CONTACT

+4969 7601; pauligk.claudia@khnw.de

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2020
• First Posted: June 25, 2020
• Study Start: December 17, 2020
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): May 1, 2027
• Last Updated: November 12, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (15)