Clinical trial NCT05264896: Perioperative FLOT vs Adjuvant XELOX for CA Stomach
Official title: Perioperative FLOT Versus Adjuvant XELOX for Locally Advanced Gastric Cancer - a Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Cancer of Stomach, Adenocarcinoma
Keywords: Gastric cancer
Cancer of esophagogastric junction
Chemotherapy
FLOT
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2022-03-03
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised controlled trial
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

1. 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
2. Surgically resectable disease based on clinical staging
3. No previous gastrectomy or chemotherapy
4. Age 18 or above but less than 80, and
5. ECOG ≤2
6. Hemoglobin \>/= 8.0 g/dL
7. Neutrophils \>/= 1.500/µl
8. Platelets ≥ 100.000/µl
9. Creatinine clearance ≥ 50 ml/min
10. Serum albumin \>25 g/L

Exclusion criteria:

1. Distant metastases, direct tumor invasion to organs not resectable by surgery
2. Hypersensitivity or contraindication against Capacitabine, 5-FU, Leucovorin, Oxaliplatin, Docetaxel
3. Active CHD, Cardiomyopathy or cardiac insufficiency stage III-IV according to NYHA
4. Peripheral polyneuropathy ≥ NCI grade II
5. 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)
6. Pregnancy or lactation
7. Malignant secondary disease, dated back \<5 years (except in-situ carcinoma of cervix uteri, adequately treated skin basal cell carcinoma)
8. Serious uncontrolled infection or cocomitant severe medical conditions

Primary outcomes:
measure: 3 year disease free survival
timeFrame: 3 years
Secondary outcomes:
measure: Overall survival
timeFrame: 3 years
measure: Adverse event of chemotherapy
timeFrame: 6 months
measure: Adverse event of surgery
timeFrame: 30 days
measure: Rate of completion of all cycles of chemotherapy
timeFrame: 1 year
measure: Postoperative hospital stay
timeFrame: 3 months
measure: Recurrence
timeFrame: 5 years
measure: Pathology - tumor regression grade
timeFrame: 30 days
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: The Chinese University of Hong Kong
Study officials:
affiliation: Chinese University of Hong Kong
name: Hon Chi Yip, FRCSEd
role: PRINCIPAL_INVESTIGATOR
References: