MAGIC vs. CROSS Upper GI - Full Text View

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:

MedlinePlus related topics: Cancer Esophageal Cancer Esophagus Disorders

Drug Information available for: Cisplatin Paclitaxel Carboplatin Epirubicin hydrochloride Epirubicin Capecitabine

U.S. FDA Resources

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:	January 2013
Estimated Primary Completion Date:	September 2021 (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.

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:

Histologically verified adenocarcinoma of the oesophagus or oesophago-gastric junction.
CT- 18FDG-PET and EUS in all patients
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)
Pre-treatment stage cT2-3, N0-1, M0
No prior abdominal or thoracic radiotherapy
Male/female patients aged >18 years.
WHO Performance Status 0, 1 or 2
ASA I-II
Completion of baseline quality of life questionnaire (EORTC QLQ C30).
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).
Adequate respiratory function. Patients should have pulmonary function tests completed with FEV1 > 1.5L
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).
Adequate renal function: glomerular filtration rate >60ml/minute (calculated or measured).
Adequate liver function: serum bilirubin <1.5x ULN; AST <2.5x ULN and ALP <3x ULN (ULN as per institutional standard)
Written informed consent must be obtained from the patient before any study-trial specific procedures are performed.

Exclusion Criteria:

Tumours of squamous histology.
Patients with advanced inoperable or metastatic oesophageal, junctional or gastric adenocarcinoma.
Any prior chemotherapy for gastrointestinal cancer.
Prior abdominal or thoracic radiation.
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.
Clinical COPD with significant obstructive airways disease classified by FEV1 < 1.5 L or PaO2 less than 9kPa on room air
Known peripheral neuropathy >Grade 1 (absence of deep tendon reflexes as the sole neurological abnormality does not render the patient ineligible).
Known positive tests for human immunodeficiency virus (HIV) infection, , acute or chronic active hepatitis B infection.
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:	February 12, 2013
Health Authority:	Ireland: Irish Medicines Board

Additional relevant MeSH terms:

Adenocarcinoma
Adenocarcinoma, Mucinous
Esophageal Diseases
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Cystic, Mucinous, and Serous
Gastrointestinal Diseases
Digestive System Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms

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

ClinicalTrials.gov processed this record on May 16, 2013