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Gastric CancerPhase 3FLOT5NCT02578368

Chemotherapy Alone vs. Chemotherapy + Surgical Resection in Patients With Limited-metastatic Adenocarcinoma of the Stomach or Esophagogastric Junction

A Phase 3 study testing 5-Fluorouracil, Leucovorin and Oxaliplatin in people with Gastric Cancer, run by Krankenhaus Nordwest at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Previously untreated patients with limited metastatic stage (see protocol for details on criteria) will receive 4 cycles of FLOT (5-Fluorouracil, Leucovorin, Oxaliplatin and Docetaxel). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Gastric Cancer
What is being tested?
5-Fluorouracil, Leucovorin and Oxaliplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
183 participants
Where
1 siteGermany
Study dates
Feb 2016to 27 Aug 2024
Phase
Phase 3
Are there results?
None posted in the registry

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed limited metastatic gastric or GEJ adenocarcinoma.*
  • Medical and technical operability of the primary.
  • Metastatic lesions are resectable or can be controlled by local ablative procedure (central evaluation).
  • No prior chemotherapy and no prior tumor resection.
  • Female and male patients ≥ 18 years. Patients in reproductive age must be willing to use adequate contraception during the study and 3 months after the end of the study (appropriate contraception is defined as surgical sterilization (e.g., bilateral tubal ligation, vasectomy), hormonal contraception (implantable, patch, oral), and double-barrier methods (any double combination of: intrauterine device, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap)). Female patients with childbearing potential need to have a negative pregnancy test within 7 days before study start.
  • ECOG (Eastern Cooperative Oncology Group) Performance Status 0 or 1
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  • Adequate hematological, hepatic and renal function parameters:
  • Leukocytes ≥ 3000/µl
  • Platelets ≥ 100,000/µl
  • Serum creatinine ≤ 1.5 x upper limit of normal, or glomerular filtration rate (GFR) > 40 ml/min
  • Bilirubin ≤ 1.5 x upper limit of normal
  • AST (aspartate aminotransferase) and ALT (alanine transaminase) ≤ 3.5 x upper limit of normal
  • Alkaline phosphatase ≤ 6 x upper limit of normal
  • Written informed consent of the patient.
  • () Definition of the limited metastatic status is:
  • Retroperitoneal lymph node metastases (RPLM) (e.g., para-aortal, intra-aorto-caval, parapancreatic or mesenterial lymph nodes) only (Note: in duodenum invading gastric cancer, retropancreatic nodes are not regarded M1) or/and
  • at maximum one organ involved with or without RPLM according to the following schema: I. Localized potentially operable peritoneal carcinomatosis: stage P1 according to classification of the "Japanese Research Society for Gastric Cancer" (Clinically visible carcinomatosis of the peritoneum or of the pleura and >P1 peritoneal carcinomatosis are not allowed!) or II. Liver: maximum of 5 metastatic lesions that are potentially resectable or III. Lung: unilateral involvement, potentially resectable or IV. Uni- or bilateral Krukenberg tumors (ovarian met.) in the absence of macroscopic peritoneal carcinomatosis or V. Uni- or bilateral adrenal gland metastases or VI. Extra-abdominal lymph node metastases such as supraclavicular or cervical lymph node involvement or VII. Localized bone involvement (defined as being within one radiation field) or VIII. Other metastatic disease location that is considered limited by the investigator and is confirmed by the review committee

Who cannot join

  • Medical inoperability
  • Inability to understand the aims of the study and/or protocol procedures
  • Metastatic disease not fulfilling the criteria of limited disease mentioned in the inclusion criteria or non-metastatic stage (cM0)
  • Cirrhosis of the liver, pronounced alcohol abuse with anticipated detoxification, severe pulmonary infection with considerable reduction of pulmonary function
  • Primary not resectable
  • Hypersensitivity to 5-fluorouracil, leucovorin, oxaliplatin, or docetaxel
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  • Contraindication versus 5-fluorouracil, leucovorin, oxaliplatin, or docetaxel (see specific product information)
  • Clinically significant active coronary heart disease, cardiomyopathy or congestive heart failure, NYHA (New York Heart Association) III-IV
  • Clinically significant valvular defect
  • Past or current history of other malignancies unless 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
  • Known brain metastases
  • Other severe internal disease or acute infection
  • Peripheral polyneuropathy > NCI grade II
  • Serious hepatic impairment (AST/ALT>3.5xULN, AP>6xULN, bilirubin>1.5xULN; ULN = upper limit of normal)
  • Chronic inflammatory bowel disease
  • Any other concurrent antineoplastic treatment including irradiation
  • Participation in another clinical study
  • Pregnancy or lactation

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Krankenhaus Nordwest

    Frankfurt am Main, 60488

Other trials in Germany

About this study

Official title: Effect of Chemotherapy Alone vs. Chemotherapy Followed by Surgical Resection on Survival and Quality of Life in Patients With Limited-metastatic Adenocarcinoma of the Stomach or Esophagogastric Junction - A Phase III Trial of Arbeitsgemeinschaft Internistische Onkologie/Chirurgische Arbeitsgemeinschaft Onkologie/Chirurgische Arbeitsgemeinschaft für Den Oberen Gastrointestinaltrakt (AIO/CAO-V/CAOGI)

Previously untreated patients with limited metastatic stage (see protocol for details on criteria) will receive 4 cycles of FLOT (5-Fluorouracil, Leucovorin, Oxaliplatin and Docetaxel). Patients without disease progression will be randomized 1:1 to receive additional chemotherapy cycles (4-8 cycles of FLOT) or surgical resection followed by subsequent chemotherapy (4-8 cycles of FLOT). Main objective of the study is overall survival. Most important secondary objective is the quality of life under treatment and during follow-up.

Read the detailed description

Patients with potentially limited metastatic gastric cancer or adenocarcinoma of the gastroesophageal junction (GEJ) potentially fulfilling the selection criteria and who gave informed consent will undergo a careful screening and a central review process. 271 patients are to be allocated to the trial, of which at least 176 patients will be randomized. The primary objective is to extend overall survival, while preserving quality of life. The study has an 80% power to detect a statistically significant improvement (hazard ratio, HR 0.65) in overall survival in favor of the bimodal strategy. Quality of life (QoL) under treatment and during follow-up represents the most important secondary endpoint.

All patients enrolled will receive four cycles (= 8 weeks) of FLOT. For HER-2 (human epidermal growth factor receptor 2) positive disease, trastuzumab should be added.

After the 4th cycle of FLOT, patients will undergo a repeated imaging (esophago-gastro-duodenoscopy, CT/MRI or PET scan of the involved organs). Patients with disease progression will be taken out of the trial. Patients with stable disease, partial or complete remission will be stratified by tumor location (gastric vs. GEJ adenocarcinoma), response to preoperative FLOT (complete or partial remission vs. stable disease) and based on whether they have distant lymph node metastases only or additional organ involvement and will be randomized 1:1 to Arm A (with surgery) or B (no surgery).

Arm A:

Surgery will be scheduled 4-6 weeks after d1 of the last cycle of preoperative chemotherapy (d1 + 4-6 weeks). The protocol gives detailed recommendations for resection of the primary tumor as well as the metastases. Post-operatively, further 4-8 cycles of FLOT can be administered.

Arm B:

Patients will be treated with additional 4-8 cycles of FLOT. Surgical interventions are allowed for palliation.

In both of the arms, tumor assessments (CT/MRI or PET of the relevant organs) are performed prior to randomization and then every 3 months thereafter until progression/relapse, death or end of follow-up.

Quality of life (QoL) will be assessed at baseline, prior to randomization, and every 3 months after randomization during treatment and in the follow-up phase, together with tumor assessments.

Survival status and status on relapse/first progress of disease will be assessed every 3 months for up to 5 years after randomization.

Conditions
Gastric Cancer
Keywords
gastric cancer, perioperative, FLOT, limited metastatic, GEJ cancer
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

    2600 mg/m², d1 i.v., every 2 weeks

  • LeucovorinDrug

    Also called calcium folinate

    200 mg/m², d1, i.v., every 2 weeks

  • OxaliplatinDrug

    85 mg/m², d1, i.v., every 2 weeks

  • DocetaxelDrug

    50mg/m², d1, i.v., every 2 weeks

  • TrastuzumabDrug

    4 mg/kg BW (6 mg loading dose at 1st administration), i.v. for 1 h, d1, i.v., every two weeks

  • sodium folinateDrug

    can be used to replace leucovorin (calcium folinate)

  • SurgeryProcedure or surgery

    Aim of surgical resection is a complete (R0) resection of the primary tumor and the metastases or a complete macroscopic cytoreduction of the metastases.

Study groups in NCT02578368
Study groupRoleWhat they receive
Arm A: FLOT chemotherapy + surgery (OP)Experimental4 cycles (8 weeks) FLOT pre-OP - surgery - 4-8 cycles FLOT (8-16 weeks) post-OP Docetaxel (50 mg/m2) in 250 ml sodium chloride (NaCl) 0.9% i.v. for 1 h, d1; Oxaliplatin (85 mg/m2) in 500 ml G5% (glucose 5%) i.v. for 2 h, d1; Leucovorin (Ca-folinate) (200 mg/m2) in 250 ml NaCl 0.9% i.v. for 1 h, d1*; 5-FU (2600 mg/m2) continuous infusion for 24 h, d1; Repeated every two weeks (qd15). * Leucovorin can be replaced by sodium folinate. Dose adjustment necessary if levo-leucovorin is used instead of racemic leucovorin mixture. For HER-2 positive disease, trastuzumab should be added: Trastuzumab 4 mg/kg body weight (6 mg loading dose at 1st administration), i.v. for 1 h, d1 For PD-L1 positive disease (CPS ≥ 5), nivolumab can be added according to SmPC: Nivolumab 240 mg i.v. for 30 min, d1, repeated every two weeks (q15d)
Receives: Drug: 5-Fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Docetaxel; Drug: Trastuzumab; Drug: sodium folinate; Procedure: Surgery
Arm B: FLOT chemotherapy aloneActive comparator4 cycles (8 weeks) FLOT followed by further 4-8 cycles FLOT (8-16 weeks) Docetaxel (50 mg/m2) in 250 ml sodium chloride (NaCl) 0.9% i.v. for 1 h, d1; Oxaliplatin (85 mg/m2) in 500 ml G5% (glucose 5%) i.v. for 2 h, d1; Leucovorin (Ca-folinate) (200 mg/m2) in 250 ml NaCl 0.9% i.v. for 1 h, d1*; 5-FU (2600 mg/m2) continuous infusion for 24 h, d1; Repeated every two weeks (qd15). * Leucovorin can be replaced by sodium folinate. Dose adjustment necessary if levo-leucovorin is used instead of racemic leucovorin mixture. For HER-2 positive disease, trastuzumab should be added: Trastuzumab 4 mg/kg body weight (6 mg loading dose at 1st administration), i.v. for 1 h, d1 For PD-L1 positive disease (CPS ≥ 5), nivolumab can be added according to SmPC: Nivolumab 240 mg i.v. for 30 min, d1, repeated every two weeks (q15d)
Receives: Drug: 5-Fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Docetaxel; Drug: Trastuzumab; Drug: sodium folinate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall survival (OS)

    Measured: up to 5 years follow-up

Secondary outcomes (8)

  1. Quality of life (QoL) adjusted OS

    Measured: up to 5 years follow-up

  2. QoL-response

    Measured: up to 5 years follow-up

  3. QoL mean scores

    Measured: up to 5 years follow-up

  4. OS in patients with lymph node metastases only

    Measured: up to 5 years follow-up

  5. Progression free survival (PFS)

    Measured: up to 5 years follow-up

  6. Surgical morbidity

    Measured: up to 2 months after surgery

  7. Surgical mortality

    Measured: up to 2 months after surgery

  8. Toxicity - Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    Measured: From signature of the informed consent form (ICF) up to 30 days after last administration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Oct 2015 (estimated)
  2. Study startFeb 2016
  3. Primary completion27 Aug 2024
  4. Study completion27 Aug 2024

Resources

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
183 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02578368
Sponsor's protocol ID
RENAISSANCE
Acronym
FLOT5
Status last verified
Nov 2024
First submitted
12 Oct 2015
Last updated
12 Nov 2024
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No: No IPD will be shared

Publications

  • Al-Batran SE, Goetze TO, Mueller DW, Vogel A, Winkler M, Lorenzen S, Novotny A, Pauligk C, Homann N, Jungbluth T, Reissfelder C, Caca K, Retter S, Horndasch E, Gumpp J, Bolling C, Fuchs KH, Blau W, Padberg W, Pohl M, Wunsch A, Michl P, Mannes F, Schwarzbach M, Schmalenberg H, Hohaus M, Scholz C, Benckert C, Knorrenschild JR, Kanngiesser V, Zander T, Alakus H, Hofheinz RD, Roedel C, Shah MA, Sasako M, Lorenz D, Izbicki J, Bechstein WO, Lang H, Moenig SP. The RENAISSANCE (AIO-FLOT5) trial: effect of chemotherapy alone vs. chemotherapy followed by surgical resection on survival and quality of life in patients with limited-metastatic adenocarcinoma of the stomach or esophagogastric junction - a phase III trial of the German AIO/CAO-V/CAOGI. BMC Cancer. 2017 Dec 28;17(1):893. doi: 10.1186/s12885-017-3918-9.

    PubMed 29282088

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, run by Krankenhaus Nordwest at 1 site 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 17 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: finished, 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 1 site 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall survival (OS) (time frame: up to 5 years follow-up). 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 NCT02578368, 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.

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