None listed
Conditions
Brief summary
This study aims to evaluate whether the addition of pre-operative chemoradiotherapy to chemotherapy is superior to chemotherapy alone in patients undergoing surgery for resectable gastric cancer. You may be eligible to join this study if you are aged 18 years or over and have a diagnosis of stomach cancer that is suitable for removal with surgery. If you join the study, you will be expected to attend the following visits over a period of approximately 28 weeks: • 1 set of screening visits over a period of 3 weeks • Up to 20 chemotherapy visits (once a week during chemotherapy) • 25 radiotherapy visits if being treated with chemoradiation (daily, Monday to Friday, for 5 weeks) • 1 set of pre-surgery visits over a period of 3 weeks • 1 surgery Following treatment, you will be expected to attend approximately 14 follow-up visits over a period of 5 years (one visit every 3-6 months). You will be asked to fill in Quality of Life questionnaires before you start treatment, twice during preoperative treatment, before surgery, around 1, 4, 6, 9 and 12 months after surgery and at each subsequent follow-up appointment until 5 years. This is so we can find out how you are feeling in yourself and the effect treatment has upon you and your daily activities. The study aims to further medical knowledge and may improve future treatment of stomach cancer.
Interventions
Group 2:
Chemotherapy:
ECF - Epirubicin (E) 50 mg/m2 IV day 1, Cisplatin (C) 60 mg/m2 IV day 1, 5-Fluorouracil (F)200 mg/m2/d IV 21 day continuous infusion
or
ECX - Epirubicin 50 mg/m2 IV day 1, Cisplatin 60 mg/m2 IV day 1, Capecitabine (X = Xeloda) 625mg/m2, bid days 1-21
or
EOX - Epirubicin 50mg/m2 IV day 1, Oxaliplatin (O) 130mg/m2 IV day 1, Capecitabine 625mg/m2, bid days 1-21
or
FLOT - 5-Fluorouracil 2600 mg/m² IV 24 h infusion day 1, Leucovorin (L) 200 mg/m² IV day 1, Oxaliplatin 85
Group 2: Chemotherapy: ECF - Epirubicin (E) 50 mg/m2 IV day 1, Cisplatin (C) 60 mg/m2 IV day 1, 5-Fluorouracil (F)200 mg/m2/d IV 21 day continuous infusion or ECX - Epirubicin 50 mg/m2 IV day 1, Cisplatin 60 mg/m2 IV day 1, Capecitabine (X = Xeloda) 625mg/m2, bid days 1-21 or EOX - Epirubicin 50mg/m2 IV day 1, Oxaliplatin (O) 130mg/m2 IV day 1, Capecitabine 625mg/m2, bid days 1-21 or FLOT - 5-Fluorouracil 2600 mg/m² IV 24 h infusion day 1, Leucovorin (L) 200 mg/m² IV day 1, Oxaliplatin 85 mg/m² IV day 1, Docetaxel (T) 50 mg/m² IV day 1 Pre-operative chemoradiotherapy (CRT): Continuous infusional 5-FU- 200 mg/m2/day, 7 days per week, throughout the entire period of radiotherapy via CADD pump (or other infuser device depending on usual practice) through a PICC line. or Capecitabine 825mg/m2, bid, days 1 to 5 each week of RT (without weekends) Radiotherapy: 45 Gy of radiation in 25 fractions, five days per week for five weeks. Surgery: The acceptable resections are a total gastrectomy, a subtotal gastrectomy, and an esophago-gastrectomy (Ivor-Lewis esophago-gastrectomy for gastroesophageal junction [GEJ] cancers [Siewert Type II and Siewert Type III] invading up to but no more than 2cm of the lower esophagus). It is considered that the minimum extent of the operation should be a D1+ lymph node dissection but it is recommended that a D2 dissection should be performed or a D1+ for GEJ cancers requiring an esophago-gastrectomy. Treatment schedule: Patients randomised to Group 2 will receive 2 cycles of ECF or EOX at three-weekly intervals pre-operatively or 3 cycles of FLOT at two-weekly intervals, then 2-4 week break between last cycle of chemotherapy and chemoradiotherapy. Following chemoradiotherapy patients should have up to 6 weeks break between chemoradiotherapy and surgery and then 3 cycles of ECF or EOX or 4 cycles of FLOT should be commenced post-operatively between 4-10 weeks after surgery.
Sponsors
Australasian Gastro-Intestinal Trials Group (AGITG)
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically proven adenocarcinoma of the stomach or gastroesophageal junction that is: a. Stage IB (T1N1 only, T2N0 not eligible) – IIIC, i.e. T3 – T4 and/or N +ve, according to AJCC 7th edition. b. Considered operable following initial staging investigations (surgeon believes that an R0 resection can be achieved). (Gastroesophageal tumours are defined as tumours that arise in the cardia or at the GEJ that do not involve more than 2cm of the lower esophagus, i.e. Siewert Type II and Siewert Type III) 2. Age >= 18 years 3. ECOG performance status 0-1 4. Adequate organ function defined as follows: Bone marrow: Haemoglobin >= 90 g/L Absolute neutrophil count (ANC) >= 1.5 x 109 /L White blood cell count >= 3 x 109 /L Platelet count >= 100 x 109 /L Hepatic: Serum bilirubin <= 1.5 x ULN AST and/or ALT <= 3.0 x ULN Renal: Serum creatinine <= 0.150 mmol/L, and calculated creatinine clearance >= 50mL/min. 5. Disease which can be radically treated with radiotherapy to 45 Gy with standard fractionation 6. Any patient with a history of ischaemic heart disease and abnormal ECG, or who is over 60 years of age should have a pre-treatment evaluation of cardiac function with a MUGA scan or echocardiogram. Patients will only be included if the left ventricular ejection fraction is >= 50%. 7. Written informed consent obtained before randomization. 8. Negative pregnancy test for women of childbearing potential within 7 days of commencing study treatment. Males and females of reproductive potential must agree to practice adequate contraceptive measures
Exclusion criteria
None of the following must apply: 1. Evidence of metastatic disease 2. Prior chemotherapy or radiotherapy 3. Patients with a past history of cancer in the 5 years before randomization except for the following. Patients with squamous or basal cell carcinoma of the skin that has been effectively treated, and patients with carcinoma in situ of the cervix that has been treated by operation only are eligible, even if they were diagnosed and treated within the 5 years before randomization. 4. Patients with other significant underlying medical conditions that may be aggravated by the study treatment or are not controlled. 5. Pregnant or lactating females or female patients of childbearing potential who have not been surgically sterilized or are without adequate contraceptive measures. 6. Cardiac failure and other contraindications to epirubicin. 7. Patients with impaired gastrointestinal absorption for whatever reason. 8. Patients medically unfit for cisplatin chemotherapy due to one or more of the following reasons: a. Clinically significant sensori-neural hearing impairment (audiometric abnormalities without corresponding clinical deafness will not be regarded as a contraindication to cisplatin) b. Severe tinnitus c. Renal impairment (GFR<= 50ml/min) d. Peripheral neuropathy => grade 2 e. Inability to tolerate intravenous hydration e.g due to cardiac disease f. Co-morbidities (based on clinical judgement by the investigator) that in the view of the investigator would preclude the safe administration of cisplatin.
Outcome results
None listed