Perioperative Chemotherapy With FOLFIRINOX Regimen or FLOT Regimen for Resectable Gastric or Esophagogastric Junction Adenocarcinoma (Type II-III): Open-label Randomized Phase 2/3 Trial
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Blokhin's Russian Cancer Research Center
- Enrollment
- 538
- Locations
- 1
- Primary Endpoint
- median overall survival
Overview
Brief Summary
Patients with resectable adenocarcinoma of the stomach or the esophagogastric junction (II-III type by Siewert) without previous therapy will be treated with one of two chemotherapy combinations before and after surgery. One half of the patients gets 5-Fluorouracil (5-FU), Leucovorin, Oxaliplatin and Docetaxel (FLOT), the others 5-Fluorouracil (5-FU), Leucovorin, Oxaliplatin and Irinotecan (FOLFIRINOX). Main objective of the study is median overall survival.
Detailed Description
538 Patients with resectable (cT4cN0 or cT1-4 and cN+, cM0) adenocarcinoma of the stomach or the esophagogastric junction without previous therapy will be included in this study. After randomization patients receive perioperatively 4 cycles FLOT or FOLFIRINOX, followed by a restaging of the tumour status and surgery. Subsequently another 4 cycles of FLOT or FOLFIRNOX are applicated.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •сT4 cN0 or cT1-4 cN+ histologically proven adenocarcinoma of the esophagogastric junction (Siewert type II-III) or the stomach without distant metastases (M0)
- •No previous cytostatic chemotherapy or radiation therapy
- •Age 18-70 years (female and male)
- •Eastern Cooperative Oncology Group ≤ 2
- •Surgical resectability
- •Neutrophils\> 2.000/µl
- •Platelets \> 100.000/µl
- •Normal value of Serum Creatinin
- •Albumin level \> 29 г/л
- •Aspartate transaminase (AST) or alanine transaminase (ALT) less than 3 times the upper limits of normal (ULN)
Exclusion Criteria
- •Previous cytostatic chemotherapy or radiation therapy
- •Distant metastases or all primarily not resectable stages
- •Cancer relapse
- •Complicated gastric cancer (perforation, bleeding, sub or decompensated stenosis, dysphagia IV)
- •Diarrhea ≥ 2 according to the criteria of Common Terminology Criteria for Adverse Events (CTCAE) version 4.1;
- •Hypersensitivity against 5- Fluorouracil, Leucovorin, Oxaliplatin, Epirubicin and Docetaxel
- •Existence of contraindications against 5- Fluorouracil, Leucovorin, Oxaliplatin, Irinotecan or Docetaxel
- •Active coronary heart disease, Cardiomyopathy or cardiac insufficiency stage III-IV according to New York Heart Association (NYHA)
- •Severe non-surgical accompanying disease or acute infection (uncontrolled arterial hypertension, diabetes mellitus, stroke less than 6 months old, mental disorders, other tumors and others)
- •Malignant secondary disease, dated back \< 5 years (exception: In-situ-carcinoma of the cervix uteri, adequately treated skin basal cell carcinoma)
Arms & Interventions
FOLFIRINOX
Irinotecan 180mg/m2 d1, d1-2 5-FU 2450 mg/m², d1 Leucovorin 200 mg/m², d1 Oxaliplatin 85 mg/m², d1 every two weeks (q2w) 4 cycles (4-8 weeks) pre-OP and 4 cycles (6-12 weeks) post-OP
Intervention: Irinotecan (Drug)
FOLFIRINOX
Irinotecan 180mg/m2 d1, d1-2 5-FU 2450 mg/m², d1 Leucovorin 200 mg/m², d1 Oxaliplatin 85 mg/m², d1 every two weeks (q2w) 4 cycles (4-8 weeks) pre-OP and 4 cycles (6-12 weeks) post-OP
Intervention: 5-FU (Drug)
FOLFIRINOX
Irinotecan 180mg/m2 d1, d1-2 5-FU 2450 mg/m², d1 Leucovorin 200 mg/m², d1 Oxaliplatin 85 mg/m², d1 every two weeks (q2w) 4 cycles (4-8 weeks) pre-OP and 4 cycles (6-12 weeks) post-OP
Intervention: Leucovorin (Drug)
FOLFIRINOX
Irinotecan 180mg/m2 d1, d1-2 5-FU 2450 mg/m², d1 Leucovorin 200 mg/m², d1 Oxaliplatin 85 mg/m², d1 every two weeks (q2w) 4 cycles (4-8 weeks) pre-OP and 4 cycles (6-12 weeks) post-OP
Intervention: Oxaliplatin (Drug)
FLOT
d1 Docetaxel 50mg/m2, d1-2 5-FU 2600 mg/m², d1 Leucovorin 200 mg/m², d1 Oxaliplatin 85 mg/m² every two weeks (q2w) 4 cycles (4-8 weeks) pre-OP and 4 cycles (6-12 weeks) post-OP
Intervention: 5-FU (Drug)
FLOT
d1 Docetaxel 50mg/m2, d1-2 5-FU 2600 mg/m², d1 Leucovorin 200 mg/m², d1 Oxaliplatin 85 mg/m² every two weeks (q2w) 4 cycles (4-8 weeks) pre-OP and 4 cycles (6-12 weeks) post-OP
Intervention: Leucovorin (Drug)
FLOT
d1 Docetaxel 50mg/m2, d1-2 5-FU 2600 mg/m², d1 Leucovorin 200 mg/m², d1 Oxaliplatin 85 mg/m² every two weeks (q2w) 4 cycles (4-8 weeks) pre-OP and 4 cycles (6-12 weeks) post-OP
Intervention: Oxaliplatin (Drug)
FLOT
d1 Docetaxel 50mg/m2, d1-2 5-FU 2600 mg/m², d1 Leucovorin 200 mg/m², d1 Oxaliplatin 85 mg/m² every two weeks (q2w) 4 cycles (4-8 weeks) pre-OP and 4 cycles (6-12 weeks) post-OP
Intervention: Docetaxel (Drug)
Outcomes
Primary Outcomes
median overall survival
Time Frame: 2 years
Secondary Outcomes
- Pathologic complete response rate(1 month after surgery)
- Disease free survival(2 years)
- Perioperative Morbidity and Mortality(1 months after surgery)
- R0-Resection rate(1 month after surgery)