NEOadjuvant Trial in Adenocarcinoma of the oEsophagus and oesophagoGastric Junction International Study (Neo-AEGIS)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01726452|
Recruitment Status : Recruiting
First Posted : November 15, 2012
Last Update Posted : November 13, 2020
This is a multicentre phase III open-labelled, randomised controlled trial. Eligible patients will be randomised in a 1:1 fashion between neoadjuvant and adjuvant chemotherapy (Investigator's choice modified MAGIC (ECF/ECX or EOF/EOX) or FLOT regimen) and surgery or Arm B (CROSS protocol: chemotherapy with radiation therapy and surgery as per multimodal protocol).
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.
|Condition or disease||Intervention/treatment||Phase|
|Adenocarcinoma of the Oesophagus Adenocarcinoma of the Oesophago-gastric Junction Oesophageal Tumours Junctional Tumours Oesophageal Cancer||Drug: Epirubicin Drug: Cisplatin / Oxaliplatin Drug: 5 Flourouracil/ Capecitabine Radiation: (41.4 Gy/23 fractions) Drug: Paclitaxel Drug: Carboplatin Drug: Docetaxel Drug: Oxaliplatin Drug: Leucovorin Drug: 5-Fluorouracil||Phase 3|
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 modified MAGIC (ECF/ECX or EOF/EOX) or FLOT regimen and chemotherapy regimen versus the CROSS neoadjuvant chemo radiation protocol prior to surgery. Patients will be randomised to either Arm A (modified MAGIC or FLOT 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 modified MAGIC or FLOT regimen or the CROSS protocol.
Exploratory Study- Translational Research :
The collection of blood and tissue samples for storage in the bio bank for future research.
Patients enrolled in this trial at the St James's' Hospital site, 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||540 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Neo-AEGIS (NEOadjuvant Trial in Adenocarcinoma of the oEsophagus and oesophagoGastric Junction International Study): Randomised Clinical Trial of Neoadjuvant and Adjuvant Chemotherapy (Modified MAGIC or FLOT Regimen) vs. Neoadjuvant Chemoradiation (CROSS Protocol) in Adenocarcinoma of the Oesophagus and Oesophago-gastric Junction|
|Study Start Date :||August 2012|
|Estimated Primary Completion Date :||March 2023|
Experimental: A (Modified MAGIC) OR Arm A: FLOT
Modified MAGIC: The modified MAGIC regimen encompasses 3 cycles of chemotherapy pre-surgery and 3 cycles post-surgery. The regimen is a combination of epirubicin, cisplatin or oxaliplatin and a choice of 5-fluorouracil or capecitabine. Each cycle lasts 21 days.
FLOT: The FLOT regimen encompasses 8 cycles of chemotherapy in total , 4 cycles of chemotherapy pre-surgery and a further 4 cycles of chemotherapy post-surgery. Each cycle of chemotherapy lasts 14 days/2 weeks.
50mg/m2 on Day 1 of each cycle only (i.e. every 21 days)
Drug: Cisplatin / Oxaliplatin
Cisplatin, 60mg/m2 on day 1 of each cycle only (i.e. every 21 days). OR Oxaliplatin,130 mg/m2 on Day 1 of each cycle (i.e. every 21 days) The choice between administering Cisplatin or Oxaliplatin is at the discretion of the investigator.
Drug: 5 Flourouracil/ Capecitabine
5-Flourouracil 200 mg/m2/day every day for 21 days OR Capecitabine 625 mg/m2 twice daily orally). The choice between administering 5 Flourouracil or Capecitabine is at the discretion of the investigator.
Docetaxel, 50 mg/m², day 1 of each cycle (i.e. every 14 days)
85 mg/m², day 1 of each cycle (i.e. every 14 days)
200 mg/m², day 1 of each cycle (i.e. every 14 days).
2600 mg/m² Day 1 of each cycle (i.e. every 14 days) Dexamethasone or equivalent, 8mg, twice daily, Day before, day of and day after OR administered as per standard practice
Experimental: B (CROSS)
Arm B consists of the multimodal CROSS arm, which includes a combination of chemotherapy and radiotherapy prior to surgery. The patient will receive four and a half (4.5) weeks of radiation therapy (41.4 Gy/23 fractions), and 5 weekly cycles of chemotherapy. The chemotherapy and radiotherapy will run concurrently over a 4 and a half-week period. Chemotherapy is given by intravenous infusion on days 1, 8, 15, 22 and 29. The radiation will generally commence on the 1st day of treatment and will run for 4 and a half weeks as follows: days 1-5, days 8-12, days 15-19, days 22-26 and days 29-31 inclusive.
Radiation: (41.4 Gy/23 fractions)
Patient will receive 4.5 weeks of radiation therapy (41.4 Gy/23 fractions).
50mg/ m2 Paclitaxel dose administered on Days 1, 8, 15,22 and 29. Dexamethasone, Chlorphenamine and Ranitidine dose given per local standard practice. NACL infusion per local standard practice. Ondansetron dose given per local standard practice on Days 1, 8, 15, 22 and 29.
Dose determined as per calculation, infused on Days 1, 8, 15, 22 and 29
- Overall survival [ Time Frame: At end of trial- up to 3 years in follow up ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01726452
|Contact: Cancer Trials Ireland, Innovation House, Finglas road Dublin 11||+353 1 6677211|
|Contact: Cancer Trials Ireland||+353 1 6677211|
|Principal Investigator:||John V. Reynolds, Professor||Trinity Centre, St. James's Hospital, Dublin 8, Ireland|