None listed
Conditions
Brief summary
This study compares the effectiveness of pre-operative treatment with cisplatin, 5 fluorouracil and docetaxel with or without radiotherapy in treating people who have shown a poor early response to standard chemotherapy for adenocarcinoma of the oesophagus and/or gastroesophageal junction. Who is it for? You can join this study if you have localised adenocarcinoma of the oesophagus or gastroesophageal junction which is due to be treated by surgery. Trial details: After the first cycle of standard cisplatin/5-FU chemotherapy all patients will have a PET scan. Patients who have a poor response on the PET scan, will be randomly divided into two groups. One group will receive chemotherapy (cisplatin/5-FU with the addition of docetaxel) followed by surgery, and the other will receive chemotherapy (cisplatin/5-FU with the addition of docetaxel) and radiation followed by surgery. In both groups, the chemotherapy is given intravenously. In the group receiving radiation treatment, this will overlap with the chemotherapy treatment. The study aims to evaluate the response to the different therapy regimens, by comparing pathology samples, looking at the response on PET scans, toxicity, survival rates and quality of life.
Interventions
Randomised study of patients that have not shown early response to standard chemotherapy. All participants receive the standard treatment of a 21 day cycle of Cisplatin 80mg/m2 (intravenously infused over 2 hours) Day 1 and 5-Fluorouracil 1000 mg/m2 (continuous infusion) Days 1-4. All participants are restaged at day 15 with Positron Emission Tomography (PET). If significant response then standard treatment is repeated over another 21 day cycle. However if no significant response, subjects will
Randomised study of patients that have not shown early response to standard chemotherapy. All participants receive the standard treatment of a 21 day cycle of Cisplatin 80mg/m2 (intravenously infused over 2 hours) Day 1 and 5-Fluorouracil 1000 mg/m2 (continuous infusion) Days 1-4. All participants are restaged at day 15 with Positron Emission Tomography (PET). If significant response then standard treatment is repeated over another 21 day cycle. However if no significant response, subjects will be randomised to receive either 2 x 21 day cycles of Cisplatin 60mg/m2 (intravenously infused over 2 hours) on day 22 & day 50, Docetaxel 35mg/m2 (intravenously infused over 1 hour) on Day 22, 29, 36, 50 ,57 & 64 & 5-Fluorouracil 150mg/m2 continuous intravenous infusion for 6 weeks starting Day 22 OR Cisplatin 60mg/m2 (intravenously infused over 2 hours) on day 22 & day 50, Docetaxel 35mg/m2 (intravenously infused over 1 hour) on Day 22, 29, 36, 50 ,57 & 64 & 5-Fluorouracil 150mg/m2 continuous intravenous infusion for 6 weeks starting Day 22 plus radiation 45Gy/25Fr starting Day 22. Radiation will be administered once daily, Monday to Friday on 25 occasions. All participants will have surgery in an attempt for complete resection, 4 - 8 weeks after completion of neoadjuvant therapy. The operation should aim to remove the tumour in total, with an adequate margin in each direction. This may be done as a subtotal esophagectomy with proximal gastric resection and a right intrathoracic oesophago-gastrostomy (Ivor–Lewis procedure), a subtotal oesophagectomy with proximal gastric resection and a cervical oesophago-gastrostomy (McKeon procedure). This is a complicated surgery often taking more than 6 hours.
Sponsors
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 invasive adenocarcinoma of the oesophagus or gastroesophageal junction. 2. Tumour thought to be T2 or greater or T1 tumours that are poorly differentiated or thought to be node-positive. 3. Technically resectable disease, as assessed in consultation with the intended surgeon. 4. Tumour is sufficiently F-18 fluorodeoxyglucose (FGD) avid on the initial staging PET scan to provide sufficient contrast between tumour and the surrounding normal tissues so that a response to the neoadjuvant therapy may be assessed. 5. Written informed consent of the patient according to local ethics committee guidelines. 6. Medically fit for surgical resection, defined as having adequate cardiopulmonary function and Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Exclusion criteria
1. Evidence of extrathoracic or extragastric spread apart from perigastric or mediastinal nodes, which are resectable. (Supraclavicular nodes renders the patient ineligible) 2. Tumour is located in the cervical oesophagus requiring pharyngolaryngectomy. 3. Tumour is predominantly within the stomach ie. most of the tumour is not involving the oesophagus or gastroesophageal junction. 4. Evidence of tracheo- or broncho oesophageal fistula. 5. Adequate haematological function. 6. Adequate renal function 7. Adequate liver function 8. Previous radiation therapy to the chest, previous chemotherapy within the last 5 years. 9. Previous malignancy for the previous 5 years apart from non metastatic Squamous Cell Carcinoma of the skin, Basal Cell Carcinoma or carcinoma in situ of the cervix. 10. Pregnant, lactating or inadequate contraception.
Outcome results
None listed