Cancer of Stomach, AdenocarcinomaPhase 3NCT05264896
Perioperative FLOT vs Adjuvant XELOX for CA Stomach
A Phase 3 study testing 5-FU, Leucovorin, Oxaliplatin, Docetaxel and XELOX in people with Cancer of Stomach, Adenocarcinoma, run by Chinese University of Hong Kong at 1 site in Hong Kong.
Trial summary
This is a single centre randomised controlled trial, comparing perioperative FLOT versus adjuvant XELOX for locally advanced gastric and esophagogastric junction cancers. Patients with operable clinical T3 or above and N1 or above gastric and esophagastric junction cancer would be recruited. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer of Stomach, Adenocarcinoma
- What is being tested?
- 5-FU, Leucovorin, Oxaliplatin, Docetaxel and XELOX
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 1 siteHong Kong
- Study dates
- 21 Mar 2022to 31 Dec 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Locally advanced adenocarcinoma of stomach or esophagogastric junction (Siewert type II and III), defined by clinical stage ≥T3 and/or ≥N1, in the absence of distant metastasis
- Surgically resectable disease based on clinical staging
- No previous gastrectomy or chemotherapy
- Age 18 or above but less than 80, and
- ECOG ≤2
- Hemoglobin >/= 8.0 g/dL
Show all 10Show fewer
- Neutrophils >/= 1.500/µl
- Platelets ≥ 100.000/µl
- Creatinine clearance ≥ 50 ml/min
- Serum albumin >25 g/L
Who cannot join
- Distant metastases, direct tumor invasion to organs not resectable by surgery
- Hypersensitivity or contraindication against Capacitabine, 5-FU, Leucovorin, Oxaliplatin, Docetaxel
- Active CHD, Cardiomyopathy or cardiac insufficiency stage III-IV according to NYHA
- Peripheral polyneuropathy ≥ NCI grade II
- Severe liver dysfunction (i) ALT >3 x upper limit of normal, and/ or (ii) total bilirubin >1.5 x upper limit of normal (subjects with Gilbert Syndrome with total bilirubin level of >/= 3.0 x upper limit of normal)
- Pregnancy or lactation
- Malignant secondary disease, dated back <5 years (except in-situ carcinoma of cervix uteri, adequately treated skin basal cell carcinoma)
- Serious uncontrolled infection or cocomitant severe medical conditions
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Hong Kong1 site, 1 recruiting
- Recruiting
The Chinese University of Hong Kong
Hong Kong
Hon Chi Yip, FRCSEd, +85235052627, hcyip@surgery.cuhk.edu.hk
About this study
Official title: Perioperative FLOT Versus Adjuvant XELOX for Locally Advanced Gastric Cancer - a Randomized Controlled Study
This is a single centre randomised controlled trial, comparing perioperative FLOT versus adjuvant XELOX for locally advanced gastric and esophagogastric junction cancers. Patients with operable clinical T3 or above and N1 or above gastric and esophagastric junction cancer would be recruited. Participants would be randomised to perioperative FLOT versus adjuvant XELOX with curative radical gastrectomy. Primary outcome would be 3 year Disease Free Survival. It was calculated that 110 patients would be required to demonstrate the study hypothesis.
Read the detailed description
The use of perioperative chemotherapy / chemoradiation for locally advanced cancer of the stomach and esophagogastric junction has been advocated in the past 2 decades. Randomized studies from Asia, Europe and the United States all demonstrated superior disease free survival with the use of perioperative therapy1-4. While radical gastrectomy plus D2 lymphadenectomy is the standard treatment in the treatment algorithm, the regimen of perioperative therapy has not been standardized. Earlier studies conducted in Europe and the United States using perioperative Epirubicin, Cisplatin, 5-FU (ECF) or postoperative chemoradiation were criticized owing to inadequate lymph node dissection. Adjuvant chemotherapy with either combination Capacitabine and Oxaliplatin or single agent S-1 has been proven in large prospective randomized studies in Asia, and these regimens are most commonly utilized currently.
Perioperative combination chemotherapeutic regimen using 5-FU, Leucovorin, Oxaliplatin and Docetaxel (FLOT) has been recently recommended in European countries. Initial phase II study demonstrated a dramatic improvement in complete tumor response rate (TRG1a) at 20% compared with 6% for ECF5. Results from a phase III randomized study showed superior overall survival using FLOT when compared with ECF (Median survival ECX/ECF 35months, FLOT 50 months, p=0.012)6. Radical surgery has been standardized in these recent studies. Another randomized study from Asia reported superior disease free survival when Docetaxel, Oxaliplatin and S-1 were used as pre-operative chemotherapy plus adjuvant S-1 monotherapy compared with S-1 monotherapy alone. (NCT01515748, abstract at ESMO 2019, Spain)
The main advantages of perioperative chemotherapy include downstaging of the tumor allowing easier and more complete surgical resection. The compliance rate to preoperative chemotherapy is also generally higher than postoperative therapy. Some may propose that it may also aid in selecting appropriate cases for radical surgery, thus avoiding unnecessary surgery in those who progress quickly. However, the potential drawback of such treatment regimen includes higher risk of surgery after chemotherapy and potential delay of curative surgery.
There is currently lack of prospective comparative data between adjuvant XELOX and perioperative FLOT. Our institution decided to conduct the current study to compare the survival outcomes of locally advanced cancer of stomach and esophagogastric junction after perioperative FLOT or adjuvant XELOX plus radical surgery.
- Conditions
- Cancer of Stomach, Adenocarcinoma
- Being tested
- 5-FU, Leucovorin, Oxaliplatin, Docetaxel, XELOX
- Keywords
- Gastric cancer, Cancer of esophagogastric junction, Chemotherapy, FLOT
- Medical subject headings
- Stomach Neoplasms, Adenocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-FU, Leucovorin, Oxaliplatin, DocetaxelDrug
FLOT 4 cycles pre and post radical gastrectomy
XELOXDrug
XELOX 8 cycles post radical gastrectomy
| Study group | Role | What they receive |
|---|---|---|
| FLOT | Experimental | Patients randomized to the FLOT arm would receive perioperative FLOT
Regimen:
* Docetaxel 50mg/m2, d1
* 5-FU 2600 mg/m², d1
* Leucovorin 200 mg/m², d1
* Oxaliplatin 85 mg/m², d1
* Every two weeks 4 cycles pre-op and 4 cycles post-op
Granulocyte colony stimulating factor (GCSF) at 30 mu s.c. daily from Day 4 to Day 7 is recommended.
Two weeks after completion of the 4 cycles of pre-op chemotherapy, reassessment endoscopy and CT scan would be performed. Surgery would be performed 4 weeks after pre-op chemotherapy if no distant metastasis was found on CT scan.
Post-op adjuvant FLOT (x 4 cycles) will be started within 10 weeks after surgery. Receives: Drug: 5-FU, Leucovorin, Oxaliplatin, Docetaxel |
| XELOX | Active comparator | Patients randomized to adjuvant XELOX arm would receive chemotherapy after surgery.
* Capecitabine - 1,000 mg/m² twice daily.
* Oxaliplatin - IV infusion, 130mg/m² Receives: Drug: XELOX |
What is being measured
The primary outcome is the main question the study is designed to answer.
3 year disease free survival
3 year disease free survival (%)
Measured: 3 years
Secondary outcomes (7)
Overall survival
Overall survival (%)
Measured: 3 years
Adverse event of chemotherapy
Adverse event of chemotherapy (%)
Measured: 6 months
Adverse event of surgery
Adverse event of surgery (%)
Measured: 30 days
Rate of completion of all cycles of chemotherapy
Completion rate of all cycles of chemo (%)
Measured: 1 year
Postoperative hospital stay
Postoperative hospital stay (days)
Measured: 3 months
Recurrence
Rate of Locoregional or distant recurrence
Measured: 5 years
Pathology - tumor regression grade
Pathology - Tumor Regression Grade (Based on Becker's scale) TRG 1a was defined as complete tumor regression without residual tumor; TRG 1b was defined as <10% residual tumor per tumor bed, like a subtotal tumor regression. TGR 2 illustrated a partial tumor regression with 10-50% residual tumor and at the findings of >50% residual tumor cells with or without signs of treatment effect the tumor regression was classified as TRG 3
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2022
- Study start21 Mar 2022
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cancer of Stomach, AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by Chinese University of Hong KongThe sponsor's other registered studies.
- 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
- Model description
- Randomised controlled trial
- Masking
- None (open label)
- Enrolment
- 110 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hon Chi Yip, Chinese University of Hong Kong
- Investigators
- Hon Chi Yip, FRCSEd, Principal investigator, Chinese University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05264896
- Sponsor's protocol ID
- CRE 2020.500
- Status last verified
- Sep 2023
- First submitted
- 22 Feb 2022
- Last updated
- 7 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Perioperative FLOT Versus Adjuvant XELOX for Locally Advanced Gastric Cancer - a Randomized Controlled Study
- ClinicalTrials.gov ID
- NCT05264896
- Acronym / sponsor ID
- CRE 2020.500
- Conditions
- Cancer of Stomach, Adenocarcinoma
- Keywords
- Gastric cancer, Cancer of esophagogastric junction, Chemotherapy, FLOT
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 110 participants (estimated)
- Lead sponsor
- Chinese University of Hong KongUniversity, hospital or other
- Study start
- 21 Mar 2022 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 3 Mar 2022 (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 single centre randomised controlled trial, comparing perioperative FLOT versus adjuvant XELOX for locally advanced gastric and esophagogastric junction cancers. Patients with operable clinical T3 or above and N1 or above gastric and esophagastric junction cancer would be recruited. Participants would be randomised to perioperative FLOT versus adjuvant XELOX with curative radical gastrectomy. Primary outcome would be 3 year Disease Free Survival. It was calculated that 110 patients would be required to demonstrate the study hypothesis.
Detailed description
The use of perioperative chemotherapy / chemoradiation for locally advanced cancer of the stomach and esophagogastric junction has been advocated in the past 2 decades. Randomized studies from Asia, Europe and the United States all demonstrated superior disease free survival with the use of perioperative therapy1-4. While radical gastrectomy plus D2 lymphadenectomy is the standard treatment in the treatment algorithm, the regimen of perioperative therapy has not been standardized. Earlier studies conducted in Europe and the United States using perioperative Epirubicin, Cisplatin, 5-FU (ECF) or postoperative chemoradiation were criticized owing to inadequate lymph node dissection. Adjuvant chemotherapy with either combination Capacitabine and Oxaliplatin or single agent S-1 has been proven in large prospective randomized studies in Asia, and these regimens are most commonly utilized currently.
Perioperative combination chemotherapeutic regimen using 5-FU, Leucovorin, Oxaliplatin and Docetaxel (FLOT) has been recently recommended in European countries. Initial phase II study demonstrated a dramatic improvement in complete tumor response rate (TRG1a) at 20% compared with 6% for ECF5. Results from a phase III randomized study showed superior overall survival using FLOT when compared with ECF (Median survival ECX/ECF 35months, FLOT 50 months, p=0.012)6. Radical surgery has been standardized in these recent studies. Another randomized study from Asia reported superior disease free survival when Docetaxel, Oxaliplatin and S-1 were used as pre-operative chemotherapy plus adjuvant S-1 monotherapy compared with S-1 monotherapy alone. (NCT01515748, abstract at ESMO 2019, Spain)
The main advantages of perioperative chemotherapy include downstaging of the tumor allowing easier and more complete surgical resection. The compliance rate to preoperative chemotherapy is also generally higher than postoperative therapy. Some may propose that it may also aid in selecting appropriate cases for radical surgery, thus avoiding unnecessary surgery in those who progress quickly. However, the potential drawback of such treatment regimen includes higher risk of surgery after chemotherapy and potential delay of curative surgery.
There is currently lack of prospective comparative data between adjuvant XELOX and perioperative FLOT. Our institution decided to conduct the current study to compare the survival outcomes of locally advanced cancer of stomach and esophagogastric junction after perioperative FLOT or adjuvant XELOX plus radical surgery.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomised controlled trial
| Arm | Type | Receives |
|---|---|---|
| FLOT | Experimental | Drug: 5-FU, Leucovorin, Oxaliplatin, DocetaxelPatients randomized to the FLOT arm would receive perioperative FLOT Regimen: * Docetaxel 50mg/m2, d1 * 5-FU 2600 mg/m², d1 * Leucovorin 200 mg/m², d1 * Oxaliplatin 85 mg/m², d1 * Every two weeks 4 cycles pre-op and 4 cycles post-op Granulocyte colony stimulating factor (GCSF) at 30 mu s.c. daily from Day 4 to Day 7 is recommended. Two weeks after completion of the 4 cycles of pre-op chemotherapy, reassessment endoscopy and CT scan would be performed. Surgery would be performed 4 weeks after pre-op chemotherapy if no distant metastasis was found on CT scan. Post-op adjuvant FLOT (x 4 cycles) will be started within 10 weeks after surgery. |
| XELOX | Active comparator | Drug: XELOXPatients randomized to adjuvant XELOX arm would receive chemotherapy after surgery. * Capecitabine - 1,000 mg/m² twice daily. * Oxaliplatin - IV infusion, 130mg/m² |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Locally advanced adenocarcinoma of stomach or esophagogastric junction (Siewert type II and III), defined by clinical stage ≥T3 and/or ≥N1, in the absence of distant metastasis
- Surgically resectable disease based on clinical staging
- No previous gastrectomy or chemotherapy
- Age 18 or above but less than 80, and
- ECOG ≤2
Key exclusion criteria (8 listed)
- Distant metastases, direct tumor invasion to organs not resectable by surgery
- Hypersensitivity or contraindication against Capacitabine, 5-FU, Leucovorin, Oxaliplatin, Docetaxel
- Active CHD, Cardiomyopathy or cardiac insufficiency stage III-IV according to NYHA
- Peripheral polyneuropathy ≥ NCI grade II
- Severe liver dysfunction (i) ALT >3 x upper limit of normal, and/ or (ii) total bilirubin >1.5 x upper limit of normal (subjects with Gilbert Syndrome with total bilirubin level of >/= 3.0 x upper limit of normal)
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-FU, Leucovorin, Oxaliplatin, DocetaxelFLOT 4 cycles pre and post radical gastrectomy | Drug | FLOT |
| XELOXXELOX 8 cycles post radical gastrectomy | Drug | XELOX |
Primary outcome
3 year disease free survival
Time frame: 3 years
3 year disease free survival (%)
7 secondary outcomes
Overall survival
Time frame: 3 years
Adverse event of chemotherapy
Time frame: 6 months
Adverse event of surgery
Time frame: 30 days
Rate of completion of all cycles of chemotherapy
Time frame: 1 year
Postoperative hospital stay
Time frame: 3 months
Recurrence
Time frame: 5 years
Pathology - tumor regression grade
Time frame: 30 days
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 7 Sep 2023.
- Individual participant dataSharing planned: No
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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.
Hon Chi Yip, FRCSEd principal investigator
Chinese University of Hong Kong
1 site 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-FU, Leucovorin, Oxaliplatin, Docetaxel and XELOX in people with Cancer of Stomach, Adenocarcinoma, run by Chinese University of Hong Kong at 1 site in Hong Kong.
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 10 inclusion and 8 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 7 Sep 2023. 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 Hong Kong. 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 Hon Chi Yip, FRCSEd (35052627, hcyip@surgery.cuhk.edu.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
3 year disease free survival (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Sep 2023.