Perioperative FLOT vs Adjuvant XELOX for CA Stomach

NCT ID: NCT05264896

Last Updated: 2023-09-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 110 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-21
• Study Completion Date: 2027-12-31

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.

Conditions

Cancer of Stomach, Adenocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

FLOT

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.

Group Type: EXPERIMENTAL

5-FU, Leucovorin, Oxaliplatin, Docetaxel

Intervention Type: DRUG

FLOT 4 cycles pre and post radical gastrectomy

XELOX

Patients randomized to adjuvant XELOX arm would receive chemotherapy after surgery.

• Capecitabine - 1,000 mg/m² twice daily.
• Oxaliplatin - IV infusion, 130mg/m²

Group Type: ACTIVE_COMPARATOR

XELOX

Intervention Type: DRUG

XELOX 8 cycles post radical gastrectomy

Interventions

5-FU, Leucovorin, Oxaliplatin, Docetaxel

FLOT 4 cycles pre and post radical gastrectomy

Intervention Type: DRUG

XELOX

XELOX 8 cycles post radical gastrectomy

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Hon Chi Yip

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hon Chi Yip, FRCSEd

Role: PRINCIPAL_INVESTIGATOR

Chinese University of Hong Kong

Locations

The Chinese University of Hong Kong

Hong Kong, , Hong Kong

Site Status: RECRUITING

Countries

Hong Kong

Central Contacts

Hon Chi Yip, FRCSEd

Role: CONTACT

hcyip@surgery.cuhk.edu.hk

35052627

Facility Contacts

Hon Chi Yip, FRCSEd

Role: primary

hcyip@surgery.cuhk.edu.hk

+85235052627

Other Identifiers

CRE 2020.500

Identifier Type: -

Identifier Source: org_study_id