MAGIC vs. CROSS Upper GI. ICORG 10-14, V3
To evaluate one, two and three year survival of patients treated with resection plus neoadjuvant and adjuvant chemotherapy versus resection plus neoadjuvant chemo radiotherapy.
To evaluate the effect of both neoadjuvant regimens on clinical and pathological response rate (in particular relief of dysphagia, improvement in health related quality of life (HRQL), endoscopic regression, and CT-PET evidence of tumour response), tumour regression grade, node-positivity, post-operative pathology, disease-free survival, time to treatment failure, toxicity, post-operative complications and Health Related Quality of Life (HRQL).
Translational Research: The collection of blood and tissue samples for storage in the bio bank for future research.
Adenocarcinoma of the Oesophagus
Adenocarcinoma of the Oesophago-gastric Junction
Drug: 5 Flourouracil/ Capecitabine
Radiation: (41.4 Gy/23 fractions)
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Randomised Clinical Trial of Neoadjuvant and Adjuvant Chemotherapy (MAGIC Regimen) vs. Neoadjuvant Chemoradiation (CROSS Protocol) in Adenocarcinoma of the Oesophagus and Oesophago-gastric Junction|
- Overall survival [ Time Frame: At end of trial- up to 3 years in follow up ] [ Designated as safety issue: No ]Overall survival will be calculated from the date of randomisation and an event registered on the date of death from any cause. Patients lost to follow up, or those with no death recorded on the day the database is frozen, will be censored on the date of last follow up.
|Study Start Date:||August 2012|
|Estimated Primary Completion Date:||January 2024 (Final data collection date for primary outcome measure)|
Experimental: A (MAGIC)
MAGIC regimen: Arm A consists of 3 cycles of chemotherapy pre-surgery and a further 3 cycles of chemotherapy post-surgery. Each cycle of chemotherapy lasts 21 days/3 weeks. The drugs used in the MAGIC regimen include Epirubicin, Cisplatin and 5-Flourouracil/ Capecitabine
50mg/m2 on Day 1 of each cycle only (i.e. every 21 days)Drug: Cisplatin
60mg/m2 on day 1 of each cycle only (i.e. every 21 days).Drug: 5 Flourouracil/ Capecitabine
5 Flourouracil(200 mg/m2/Day)as a continuous intravenous infusion every day for 21 days/3 weeks, Capecitabine (625 mg/m2 twice daily orally)for 21 days/3 weeks. The choice between administering 5 Flourouracil or Capecitabine is at the discretion of the investigator. 5 Flourouracil/ Capecitabine are given daily for the duration of each cycle (i.e. for 9 weeks pre-surgery and for 9 weeks post-surgery).
Experimental: B (CROSS)
Arm B consists of the CROSS protocol, which includes a combination of chemotherapy and radiotherapy prior to surgery. The patient will receive 5 weeks of radiation therapy and 5 weekly cycles of chemotherapy. The radiation will generally commence on the 1st day of treatment and will run for 5 weeks as follows: days 1-5, days 8-12, days 15-19, days 22-26 and days 29-31 inclusive. The chemotherapy and radiotherapy will run concurrently over a 5-week period. Chemotherapy is given by intravenous infusion on days 1, 8, 15, 22 and 29.
Radiation: (41.4 Gy/23 fractions)
patient will receive 5 weeks of radiation therapy (41.4 Gy/23 fractions).Drug: Paclitaxel
50mg/ m2 Paclitaxel dose administered on Days 1, 8, 15,22 and 29. Dexamethasone, Chlorphenamine and Ranitidine given IV half an hour before commencing Paclitaxel.Once the Paclitaxel infusion is completed NACL 0.9%,100 ml will be infused IV over half an hour.After this infusion is completed Ondansetron or its equivalent diluted in 100mls NACL 0.9% will be given IV over half an hour on Days 1, 8, 15, 22 and 29.Drug: Carboplatin
Dose determined as per calculation,infused on Days 1, 8, 15, 22 and 29.
Patients with cT2-3 N0-1 M0 adenocarcinoma of the oesophagus or junction, based on clinical, CT-PET, and EUS staging, will be randomised to the MAGIC chemotherapy regimen versus the CROSS neoadjuvant chemo radiation protocol prior to surgery. Patients will be randomised to either Arm A (MAGIC regimen of chemotherapy only and surgery) or Arm B (CROSS protocol: chemotherapy with radiation therapy and surgery as per multimodal protocol).
Eligible patients will be randomised in a 1:1 fashion between the MAGIC regimen or the CROSS protocol.
Exploratory Study- Translational Research :
All patients enrolled in this trial, will be invited to consent to having some of their tissue and blood taken for use in future research studies. Following consent from the patient, tissue biopsy of tumour and/or normal oesophageal tissue will be obtained for research at the same time as that biopsied for histological diagnosis. In addition, tumour and/or normal tissue will also be obtained following surgical resection. Patient blood samples will also be obtained, both before and during treatment. The identification of both tumour and circulating biomarkers will increase knowledge of the molecular mechanism(s) underlying treatment response in oesophageal cancer and may facilitate the identification of biomarkers predicting patient response to treatment.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01726452
|Cork University Hospital||Not yet recruiting|
|Contact: Contact person 021-4271971|
|Beaumont Hospital||Not yet recruiting|
|Contact: Contact person (01) 809 3000|
|SLRON- St Luke's Radiation Oncology Network||Recruiting|
|Contact: Contact person 01 4065000|
|Principal Investigator: Donal Hollywood, Prof|
|St. James's Hospital||Recruiting|
|Contact: Contact person 01 410 3000|
|Galway University Hospital||Not yet recruiting|
|Contact: Contact person (0)91 524222|
|Principal Investigator:||John V. Reynolds, Professor||Trinity Centre, St. James's Hospital, Dublin 8|