Gastric CancerPhase 3PREVENTNCT04447352
HIPEC + FLOT vs. FLOT Alone in Patients With Gastric Cancer and GEJ (PREVENT)
A Phase 3 study testing 5-Fluorouracil, Leucovorin and Oxaliplatin in people with Gastric Cancer and Gastroesophageal Junction Adenocarcinoma, run by Krankenhaus Nordwest at 15 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Gastric Cancer, Gastroesophageal Junction Adenocarcinoma
- What is being tested?
- 5-Fluorouracil, Leucovorin and Oxaliplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 15 sitesGermany
- Study dates
- 17 Dec 2020to 1 May 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- ECOG ≤ 1
- 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
- Laparoscopic exclusion of peritoneal carcinomatosis at initial staging, before start of FLOT chemotherapy
- 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
Who cannot join
- 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
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- 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.
- On-treatment participation in another interventional clinical study in the period 30 days prior to inclusion and during the study
- 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
- Known intraabdominal adhesion situs
- Pre-existing peritoneal seeding
Trial locations and contacts
15 sites in 1 country. Contact the study team or a site near you to ask about taking part.
15 sites in 1 country
Germany15 sites, 15 recruiting
- Recruiting
Uniklinik RWTH Aachen, AöR, Medizinische Klinik III, Studienzentrum Viszeralmedizin
Aachen, 52074
- Recruiting
Universitätsklinikum, Klinik und Poliklinik für Viszeral-, Thorax- und Gefäßchirurgie
Dresden, 01307
- Recruiting
Institute of Clinical Cancer Research (IKF), UCT - University Cancer Center, Frankfurt, Germany
Frankfurt, 60488
Thorsten O Goetze, MD, +496976014187
Claudia Pauligk, +496976013906, pauligk.claudia@khnw.de
- Recruiting
Universitätsklinikum Halle (Saale), Universitätsklinik und Poliklinik für Viszerale, Gefäß- und Endokrine Chirurgie
Halle, 06120
- Recruiting
Universitätsklinikum Leipzig, Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie
Leipzig, 04103
- Recruiting
Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Klinik für Chirurgie
Lübeck, 23538
- Recruiting
Klinikum Ludwigsburg, Klinik für Innere Medizin, Gastroenterologie, Hämato-Onkologie, Pneumologie, Diabetologie und Infektiologie
Ludwigsburg, 71640
- Recruiting
Universitätsklinikum Magdeburg
Magdeburg, 39120
- Recruiting
Klinikum rechts der Isar der TU München, Klinik und Poliklinik für Innere Medizin III
München, 81675
- Recruiting
Universitätsklinikum Münster, Klinik für Allgemein-, Viszeral- und Transplantationschirurgie
Münster, 48149
- Recruiting
Krankenhaus Barmherzige Brüder Regensburg, Klinik für Onkologie und Hämatologie
Regensburg, 93049
- Recruiting
Klinikum Südstadt Rostock, Klinik für Innere Medizin III
Rostock, 18059
- Recruiting
Universitätsklinikum Tübingen, Universitätsklinik für Allgemeine, Viszeral- und Transplantationschirurgie Chirurgische Studienzentrale
Tübingen, 72076
- Recruiting
Marien-Hospital Witten
Witten, 58452
- Recruiting
Universitätsklinikum Würzburg, Chirurgische Klinik I, Chirurgisches Studienzentrum
Würzburg, 97080
About this study
Official title: 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 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.
Read the detailed description
This is a multicenter, randomized, controlled, open-label study including patients with localized and locally advanced diffuse and mixed type adenocarcinoma of the stomach and Type II/III GEJ scheduled to receive perioperative chemotherapy combined with intraoperative HIPEC procedure.
The scope of the trial is to evaluate the efficacy as well as the safety and tolerability of the combination of perioperative chemotherapy combined with an intraoperative HIPEC for resectable diffuse and mixed type gastric and GEJ (types II/III) adenocarcinoma. Intraoperative hyperthermic chemoperfusion is summarized under the abbreviation HIPEC in the following.
Patients with localized and locally 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.
All enrolled patients will have received 3-6 pre-operative cycles (de-escalation or dose modification allowed) of biweekly FLOT (Docetaxel 50 mg/m² in 250 ml NaCl 0.9%, iv over 1 h; Oxaliplatin 85 mg/m² in 500 ml G5%, iv over 2h; Leucovorin 200 mg/m² in 250 ml NaCl 0.9%, iv over 30 min; 5-FU 2600 mg/m², iv over 24 h, q2wk) in the preoperative treatment phase.
After completion of neoadjuvant FLOT- therapy followed by pre-operative tumor assessment, (also including diagnostic laparoscopy prior to start of FLOT), patients without disease progression (expected to be approximately 90% of the patients) will be included into the trial, stratified by initial clinical stage (N- vs. N+), histological type of tumor (Lauren classification diffuse vs. mixed) and study site.
Patients will be randomized 1:1 to receive either postoperative FLOT (Arm A) or postoperative FLOT + intraoperative HIPEC (Arm B).
Arm A (FLOT) Surgery in Arm A is planned to occur 4 to 6 weeks after d1 of last FLOT. Surgery is carried out in kind of gastrectomy, transhiatal extended gastrectomy. Following surgery, patients will receive four further 2-week treatment cycles FLOT in the post-operative treatment phase. Post-operative treatment should start 6 to 8 weeks, but at maximum 12 weeks after surgery.
Arm B (FLOT/ HIPEC) Surgery in Arm B is planned to occur 4 to 6 weeks after d1 of last FLOT. Surgery is carried out in kind of gastrectomy, transhiatal extended gastrectomy. Surgery will be combined with an intraoperative Hyperthermic IntraPEritoneal Chemoperfusion (HIPEC) including cisplatin solution administered at a temperature of 42°C for 90 minutes. Following surgery, patients will receive four further 2-week treatment cycles FLOT in the post-operative treatment phase. Post-operative treatment should start 6 to 8 weeks, but at maximum 12 weeks after surgery.
In both of the arms, tumor assessments (CT or MRI) are performed before randomization prior to surgery, and then every 3 months (radiological tumor assessment) thereafter until progression/relapse, death or end of follow-up. A change from CT into MRI in the follow up period is possible at any time.
During treatment, clinical visits (blood cell counts, detection of toxicity) occur prior to every treatment dose. Safety of FLOT/ HIPEC will be monitored continuously by careful monitoring of all adverse events (AEs) and serious adverse events (SAEs) reported.
The phase III design starts with a safety run-in phase. After 20 patients had curatively intended resection in Arm B, an interim safety analysis is performed that shows feasibility, safety, and tolerability of Arm B planned at the time 8 weeks after the 20th patient in Arm B had curatively intended resection. It is not planned to discontinue recruitment for the interim safety analysis.
- Being tested
- 5-Fluorouracil, Leucovorin, Oxaliplatin, Docetaxel, Cisplatin
- Medical subject headings
- Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-FluorouracilDrug
Also called 5-FU
Day 1 q2w: 2600 mg/m² IV over 24 hours
LeucovorinDrug
Also called Calciumfolinat
Day 1 q2w: 200 mg/m² IV over 30 minutes
OxaliplatinDrug
Day 1 q2w: 85 mg/m² IV over 2 hours
DocetaxelDrug
Day 1 q2w: 50 mg/m² IV over 1 hour
CisplatinDrug
intraoperative: 75mg/m² intraabdominal solution over 1 hour and 30 minutes
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: 5-Fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Docetaxel; Drug: Cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: from randomization up to 5 years
Secondary outcomes (10)
Comparison of Overall survival (OS) in both arms
Overall survival (OS) where OS is defined as the time from randomization to death from any cause.
Measured: from randomization up to 5 years
Comparison of Overall survival rates at 3 and 5 years in both arms
OS rates at 3 \& 5 years defined as the percentage patients known to be alive after 3 and 5 years referring to the total number of patients randomized into the respective treatment arm
Measured: 3 and 5 years after randomization
Comparison of peritoneal relapse rate at 2 and 3 years in both arms
Peritoneal relapse rate defined as the percentage of patients with peritoneal relapse referring to the total number of patients randomized into the respective treatment arm
Measured: 2 and 3 years after surgery
PFS/DFS rates at 2, 3 & 5 years
PFS/DFS rates at 2, 3 \& 5 years defined as the percentage of patients without disease progression or relapse after surgery or death from any cause after 2, 3 and 5 years referring to the total number of patients randomized into the respective treatment arm
Measured: 2, 3 & 5 years after randomization
Rate of surgical serious adverse events (SAEs)
Rate of surgical serious adverse events, according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE Version 5.0) grade ≥ 3 adverse events and grade ≥ 3 laboratory toxicities.
Measured: After randomization of the patient until 30 days after last study-specific treatment
OS and PFS/DFS (medians and rates) according to subgroup (diffuse vs. mixed and gastric vs. GEJ type II/III)
PFS/DFS is defined as the time from randomization to disease progression or relapse after surgery or death from any cause and OS is defined as the time from randomization to death from any cause. OS and PFS/DFS rates are defined as the percentage of patients known to be alive or without disease progression or relapse after surgery or death from any cause, respectively, at specific timepoints and referring to the total number of patients in defined subgroups (diffuse vs. mixed and gastric vs. GEJ type II/III).
Measured: from randomization up to 5 years
Patient reported outcomes: Quality of life EORTC QLQ C30 questionnaire
The QoL analyses will include QoL mean values, QoL response and time to symptom deterioration (TTSD) defined as the time interval between randomization and the first decrease by ≥ 10-points. All randomly assigned patients with a baseline and at least one post-baseline assessment will be included in TTSD analyses. Patients without observed deterioration will be censored at the time of their last QoL assessment. Questionnaires given to the patients (validated quality of life questionnaires EORTC QLQ C30).
EORTC QLQ C30 contains 30 questions:
28 questions regarding body fitness, daily routines, restrictions at work and hobby, appetite, fatigue, cough, breathlessness, pain, tiredness, and body conditions from (1) to (4); 1 (not a bit), 2 (little), 3 (moderate), 4 (much).
2 questions regarding state of health and Quality of life with a horizontal rating from 1 to 7; 1 (very bad), 7 (excellent).
Measured: From date of screening until the date of first documented progression or last visit before date of death from any cause, whichever came first, assessed 8 weeks +/- 7 days until EOT, afterwards every 3 months up to 2 years after last patient in
Patient reported outcomes: Quality of life EORTC QLQ STO22 questionnaire
The QoL analyses will include QoL mean values, QoL response and time to symptom deterioration (TTSD) defined as the time interval between randomization and the first decrease by ≥ 10-points. All randomly assigned patients with a baseline and at least one post-baseline assessment will be included in TTSD analyses. Patients without observed deterioration will be censored at the time of their last QoL assessment. Questionnaires given to the patients (validated quality of life questionnaires EORTC QLQ STO22).
The EORTC QLQ-STO 22 module contains 22 items in a similar layout and response format to the EORTC QLQ-C30. The hypothesised scale structure of the module consists of five scales (dysphagia, eating restrictions, pain, reflux and anxiety) and three single items (dry mouth, body image and hair loss).
Measured: From date of screening until the date of first documented progression or last visit before date of death from any cause, whichever came first, assessed 8 weeks +/- 7 days until EOT, afterwards every 3 months up to 2 years after last patient in
Patient reported outcomes: VAS pain assessment form
The patient´s assessment of their current level of pain on a 100-mm horizontal VAS. The left-hand extreme of the line should be described as "no pain" and the right-hand as "unbearable pain".
Measured: From date of screening until the date of first documented progression or last visit before date of death from any cause, whichever came first, assessed 8 weeks +/- 7 days until EOT, afterwards every 3 months up to 2 years after last patient in
Rate of post-operative morbidity/mortality at day 30 after surgery acc. to Clavien-Dindo classification
Rate of post-operative morbidity/mortality will be assessed at day 30 after surgery acc. to Clavien-Dindo classification.
Measured: at day 30 after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2020
- Study start17 Dec 2020
- Primary completion1 Nov 2026 (estimated)
- Study completion1 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Gastric CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Krankenhaus Nordwest
- Sponsor type
- University, hospital or other
- Collaborators
- Deutsche Krebshilfe e.V., Bonn (Germany)
- Responsible party
- Sponsor
- Investigators
- Thorsten O Götze, MD, Principal investigator, Lead Coordinating Investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04447352
- Sponsor's protocol ID
- HIPEC/FLOT9
- Other IDs
- AIO-STO-0319/ass
- Acronym
- PREVENT
- Status last verified
- Nov 2024
- First submitted
- 17 Jun 2020
- Last updated
- 12 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No IPD will be shared.
Publications
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.
PubMed 34715810
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04447352
- Acronym / sponsor ID
- PREVENT / HIPEC/FLOT9
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Krankenhaus NordwestUniversity, hospital or other
- Collaborators
- Deutsche Krebshilfe e.V., Bonn (Germany)
- Study start
- 17 Dec 2020 (actual)
- Primary completion
- 1 Nov 2026 (estimated)
- Study completion
- 1 May 2027 (estimated)
- First posted
- 25 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a multicenter, randomized, controlled, open-label study including patients with localized and locally advanced diffuse and mixed type adenocarcinoma of the stomach and Type II/III GEJ scheduled to receive perioperative chemotherapy combined with intraoperative HIPEC procedure.
The scope of the trial is to evaluate the efficacy as well as the safety and tolerability of the combination of perioperative chemotherapy combined with an intraoperative HIPEC for resectable diffuse and mixed type gastric and GEJ (types II/III) adenocarcinoma. Intraoperative hyperthermic chemoperfusion is summarized under the abbreviation HIPEC in the following.
Patients with localized and locally 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.
All enrolled patients will have received 3-6 pre-operative cycles (de-escalation or dose modification allowed) of biweekly FLOT (Docetaxel 50 mg/m² in 250 ml NaCl 0.9%, iv over 1 h; Oxaliplatin 85 mg/m² in 500 ml G5%, iv over 2h; Leucovorin 200 mg/m² in 250 ml NaCl 0.9%, iv over 30 min; 5-FU 2600 mg/m², iv over 24 h, q2wk) in the preoperative treatment phase.
After completion of neoadjuvant FLOT- therapy followed by pre-operative tumor assessment, (also including diagnostic laparoscopy prior to start of FLOT), patients without disease progression (expected to be approximately 90% of the patients) will be included into the trial, stratified by initial clinical stage (N- vs. N+), histological type of tumor (Lauren classification diffuse vs. mixed) and study site.
Patients will be randomized 1:1 to receive either postoperative FLOT (Arm A) or postoperative FLOT + intraoperative HIPEC (Arm B).
Arm A (FLOT) Surgery in Arm A is planned to occur 4 to 6 weeks after d1 of last FLOT. Surgery is carried out in kind of gastrectomy, transhiatal extended gastrectomy. Following surgery, patients will receive four further 2-week treatment cycles FLOT in the post-operative treatment phase. Post-operative treatment should start 6 to 8 weeks, but at maximum 12 weeks after surgery.
Arm B (FLOT/ HIPEC) Surgery in Arm B is planned to occur 4 to 6 weeks after d1 of last FLOT. Surgery is carried out in kind of gastrectomy, transhiatal extended gastrectomy. Surgery will be combined with an intraoperative Hyperthermic IntraPEritoneal Chemoperfusion (HIPEC) including cisplatin solution administered at a temperature of 42°C for 90 minutes. Following surgery, patients will receive four further 2-week treatment cycles FLOT in the post-operative treatment phase. Post-operative treatment should start 6 to 8 weeks, but at maximum 12 weeks after surgery.
In both of the arms, tumor assessments (CT or MRI) are performed before randomization prior to surgery, and then every 3 months (radiological tumor assessment) thereafter until progression/relapse, death or end of follow-up. A change from CT into MRI in the follow up period is possible at any time.
During treatment, clinical visits (blood cell counts, detection of toxicity) occur prior to every treatment dose. Safety of FLOT/ HIPEC will be monitored continuously by careful monitoring of all adverse events (AEs) and serious adverse events (SAEs) reported.
The phase III design starts with a safety run-in phase. After 20 patients had curatively intended resection in Arm B, an interim safety analysis is performed that shows feasibility, safety, and tolerability of Arm B planned at the time 8 weeks after the 20th patient in Arm B had curatively intended resection. It is not planned to discontinue recruitment for the interim safety analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A - FLOT | Active comparator | Drug: 5-Fluorouracil, Drug: Leucovorin, Drug: Oxaliplatin, Drug: DocetaxelPatients 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. |
| Arm B - FLOT/HIPEC | Experimental | Drug: 5-Fluorouracil, Drug: Leucovorin, Drug: Oxaliplatin, Drug: Docetaxel, Drug: CisplatinPatients 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 5-FluorouracilAlso: 5-FUDay 1 q2w: 2600 mg/m² IV over 24 hours | Drug | Arm A - FLOT, Arm B - FLOT/HIPEC |
| LeucovorinAlso: CalciumfolinatDay 1 q2w: 200 mg/m² IV over 30 minutes | Drug | Arm A - FLOT, Arm B - FLOT/HIPEC |
| OxaliplatinDay 1 q2w: 85 mg/m² IV over 2 hours | Drug | Arm A - FLOT, Arm B - FLOT/HIPEC |
| DocetaxelDay 1 q2w: 50 mg/m² IV over 1 hour | Drug | Arm A - FLOT, Arm B - FLOT/HIPEC |
| Cisplatinintraoperative: 75mg/m² intraabdominal solution over 1 hour and 30 minutes | Drug | Arm B - FLOT/HIPEC |
Primary outcome
Comparison of progression-/disease-free survival (PFS/DFS) between arms
Time frame: from randomization up to 5 years
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.
10 secondary outcomes
Comparison of Overall survival (OS) in both arms
Time frame: from randomization up to 5 years
Comparison of Overall survival rates at 3 and 5 years in both arms
Time frame: 3 and 5 years after randomization
Comparison of peritoneal relapse rate at 2 and 3 years in both arms
Time frame: 2 and 3 years after surgery
PFS/DFS rates at 2, 3 & 5 years
Time frame: 2, 3 & 5 years after randomization
Rate of surgical serious adverse events (SAEs)
Time frame: After randomization of the patient until 30 days after last study-specific treatment
OS and PFS/DFS (medians and rates) according to subgroup (diffuse vs. mixed and gastric vs. GEJ type II/III)
Time frame: from randomization up to 5 years
Patient reported outcomes: Quality of life EORTC QLQ C30 questionnaire
Time frame: From date of screening until the date of first documented progression or last visit before date of death from any cause, whichever came first, assessed 8 weeks +/- 7 days until EOT, afterwards every 3 months up to 2 years after last patient in
Patient reported outcomes: Quality of life EORTC QLQ STO22 questionnaire
Time frame: From date of screening until the date of first documented progression or last visit before date of death from any cause, whichever came first, assessed 8 weeks +/- 7 days until EOT, afterwards every 3 months up to 2 years after last patient in
Patient reported outcomes: VAS pain assessment form
Time frame: From date of screening until the date of first documented progression or last visit before date of death from any cause, whichever came first, assessed 8 weeks +/- 7 days until EOT, afterwards every 3 months up to 2 years after last patient in
Rate of post-operative morbidity/mortality at day 30 after surgery acc. to Clavien-Dindo classification
Time frame: at day 30 after surgery
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2024.
- Derived from this study: PubMed 34715810Gotze 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.
- Individual participant dataSharing planned: No. No IPD will be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Thorsten O Götze, MD principal investigator
Lead Coordinating Investigator
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing 5-Fluorouracil, Leucovorin and Oxaliplatin in people with Gastric Cancer and Gastroesophageal Junction Adenocarcinoma, run by Krankenhaus Nordwest at 15 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Thorsten O Götze, MD (+4969 7601 ext. 4187, goetze.thorsten@khnw.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison of progression-/disease-free survival (PFS/DFS) between arms (time frame: from randomization up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04447352, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Nov 2024.