MAGIC vs. CROSS Upper GI. ICORG 10-14, V3

This study is currently recruiting participants.
Verified January 2014 by ICORG- All Ireland Cooperative Oncology Research Group
Sponsor:
Information provided by (Responsible Party):
ICORG- All Ireland Cooperative Oncology Research Group
ClinicalTrials.gov Identifier:
NCT01726452
First received: November 6, 2012
Last updated: January 24, 2014
Last verified: January 2014
  Purpose

Primary Objective:

To evaluate one, two and three year survival of patients treated with resection plus neoadjuvant and adjuvant chemotherapy versus resection plus neoadjuvant chemo radiotherapy.

Secondary Objective(s):

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).

Exploratory Objective(s):

Translational Research: The collection of blood and tissue samples for storage in the bio bank for future research.


Condition Intervention Phase
Adenocarcinoma of the Oesophagus
Adenocarcinoma of the Oesophago-gastric Junction
Oesophageal Tumours
Junctional Tumours
Oesophageal Cancer
Drug: Epirubicin
Drug: Cisplatin
Drug: 5 Flourouracil/ Capecitabine
Radiation: (41.4 Gy/23 fractions)
Drug: Paclitaxel
Drug: Carboplatin
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by ICORG- All Ireland Cooperative Oncology Research Group:

Primary Outcome Measures:
  • 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.


Estimated Enrollment: 366
Study Start Date: August 2012
Estimated Primary Completion Date: January 2024 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: Epirubicin
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.

Detailed Description:

Indication:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically verified adenocarcinoma of the oesophagus or oesophago-gastric junction.
  2. CT- 18FDG-PET and EUS in all patients
  3. Staging laparoscopy will be performed for tumours of the abdominal oesophagus, junction and proximal stomach i.e. AEG II and AEG III (at the investigators discretion)
  4. Pre-treatment stage cT2-3, N0-1, M0
  5. No prior abdominal or thoracic radiotherapy
  6. Male/female patients aged >18 years.
  7. WHO Performance Status 0, 1 or 2
  8. ASA I-II
  9. Completion of baseline quality of life questionnaire (EORTC QLQ C30).
  10. Adequate cardiac function. Patients with a cardiac history should have a cardiology review and should have a left ventricular ejection fraction > 50% (as determined by MUGA scan or ECHO).
  11. Adequate respiratory function. Patients should have pulmonary function tests completed with FEV1 > 1.5L
  12. Adequate bone marrow function: absolute neutrophil count (ANC) >1.5x10^9/l; white blood cell count >3x10^9/l; platelets >100x10^9/l; haemoglobin (Hb) >9g/dl (can be post-transfusion).
  13. Adequate renal function: glomerular filtration rate >60ml/minute (calculated or measured).
  14. Adequate liver function: serum bilirubin <1.5x ULN; AST <2.5x ULN and ALP <3x ULN (ULN as per institutional standard)
  15. Written informed consent must be obtained from the patient before any study-trial specific procedures are performed.

Exclusion Criteria:

  1. Tumours of squamous histology.
  2. Patients with advanced inoperable or metastatic oesophageal, junctional or gastric adenocarcinoma.
  3. Any prior chemotherapy for gastrointestinal cancer.
  4. Prior abdominal or thoracic radiation.
  5. Clinically significant (i.e. active) cardiac disease (e.g. symptomatic coronary artery disease or myocardial infarction within the last 12 months. Patients with any history of clinically significant cardiac failure are excluded from study entry.
  6. Clinical COPD with significant obstructive airways disease classified by FEV1 < 1.5 L or PaO2 less than 9kPa on room air
  7. Known peripheral neuropathy >Grade 1 (absence of deep tendon reflexes as the sole neurological abnormality does not render the patient ineligible).
  8. Known positive tests for human immunodeficiency virus (HIV) infection, , acute or chronic active hepatitis B infection.
  9. Any other malignancies within the last 5 years (other than curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01726452

Locations
Ireland
Cork University Hospital Not yet recruiting
Cork, Ireland
Contact: Contact person    021-4271971      
St. James's Hospital Recruiting
Dublin, Ireland
Contact: Contact person    01 410 3000      
Beaumont Hospital Not yet recruiting
Dublin, Ireland
Contact: Contact person    (01) 809 3000      
SLRON- St Luke's Radiation Oncology Network Recruiting
Dublin, Ireland
Contact: Contact person    01 4065000      
Principal Investigator: Donal Hollywood, Prof         
Galway University Hospital Not yet recruiting
Galway, Ireland
Contact: Contact person    (0)91 524222      
Sponsors and Collaborators
ICORG- All Ireland Cooperative Oncology Research Group
Investigators
Principal Investigator: John V. Reynolds, Professor Trinity Centre, St. James's Hospital, Dublin 8
  More Information

No publications provided

Responsible Party: ICORG- All Ireland Cooperative Oncology Research Group
ClinicalTrials.gov Identifier: NCT01726452     History of Changes
Other Study ID Numbers: ICORG 10-14
Study First Received: November 6, 2012
Last Updated: January 24, 2014
Health Authority: Ireland: Irish Medicines Board

Additional relevant MeSH terms:
Adenocarcinoma
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Capecitabine
Cisplatin
Epirubicin
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Antimetabolites, Antineoplastic

ClinicalTrials.gov processed this record on April 15, 2014