Clinical trial NCT01843829: A Feasibility Study of Chemo-radiotherapy to Treat Operable Oesophageal Cancer
Official title: A Randomised Phase II Study of Two Pre-operative Chemoradiotherapy Regimens (Oxaliplatin and Capecitabine Followed by Radiotherapy With Either Oxaliplatin and Capecitabine or Paclitaxel and Carboplatin) for Resectable Oesophageal Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Oesophageal Cancer
Keywords: Oesophageal cancer
Lead sponsor: Velindre NHS Trust
Sponsor class: OTHER_GOV
Collaborators: name: Cancer Research UK
First posted: 2013-05-01
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: About 7500 patients are diagnosed with oesophageal cancer each year in the UK of which less than a quarter have resectable disease at diagnosis. There is a general lack of consistency in the standard of care for patients across UK hospitals. Patients are either treated with a) chemotherapy followed by surgical removal of the tumour, or b) chemoradiotherapy followed by removal of the tumour by surgery, as part of their standard of care. Recent research supports the latter treatment, as chemoradiotherapy maybe more effective at shrinking the tumour and preventing the disease from spreading than taking chemotherapy alone. However, there is no definitive way of identifying which treatment is best without a clinical trial.

Evidence suggests that the effect of the chemoradiotherapy currently used as standard practice may be improved and the side effects reduced by using a different chemoradiotherapy combination. In this trial, eligible patients will receive 2 cycles of the same chemotherapy before being randomised to receive two different chemoradiotherapy regimens (carboplatin and paclitaxel verses oxaliplatin and capecitabine) both of which have shown promising results in previous studies. Patients will then have their tumour removed. The best chemoradiotherapy regimen will then be taken forward to a Phase III trial in which chemoradiotherapy will be compared with chemotherapy alone.

The efficacy of the regimens will be measured by counting the number of patients who i) remain free from cancer, ii)have local or distant spread of their cancer, iii) are successfully recruited and iv) experience toxicities. A specific set of toxicity criteria will be used to monitor any treatment induced side-effects and provide justification for any necessary dose modifications or withdrawal of treatment.


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed operable oesophageal cancer (adenocarcinoma)
* Tumour must be staged as a T3, 4 or N1 (using TNM6 staging) or T3, T4a or N13 using TNM7 staging)
* Maximum disease (Tumour plus nodes) length 8 cm staged with EUS and CT/PET
* WHO performance status 01
* Adequate haematological, renal, respiratory, cardiac and hepatic function
* The patient has provided written informed consent.

Exclusion Criteria:

* Histologically confirmed operable oesophageal cancer (squamous cell carcinoma)
* Uncontrolled angina pectoris, myocardial infarction within 6 months, heart failure, clinically significant uncontrolled cardiac arrhythmias, or any patient with a clinically significant abnormal ECG.
* Patients with any previous treatment for oesophageal carcinoma.
* Siewert type 3 oesophagogastric tumours.
* T4 tumours invading contiguous structures other than diaphragm, crura or mediastinal pleura.
* Patients with disease in any of the following areas on the CT scan, EUS or other staging investigation:

  1. Evidence of metastases in liver, lung, bone or other distant metastases.
  2. Abdominal para aortic lymphadenopathy \>1cm diameter on CT or \>6mm diameter on EUS.
  3. Invasion of tracheo-bronchial tree, aorta, pericardium or lung.
* Lymphadenopathy encasing the coeliac axis (as described above, patients with single nodes lying anterior to the origin of the splenic artery and anterior to the origin of the coeliac axis are not excluded).
* Any patient with a single significant medical condition which is thought likely to compromise his or her ability to tolerate any of the above therapies.
* Specific contraindications to surgery, chemotherapeutic agents (including known allergies to chemotherapy) or radiotherapy.
* Pregnant or lactating women and fertile women who will not be using adequate contraception during the trial.

Primary outcomes:
measure: Efficacy
timeFrame: 24 months
Secondary outcomes:
measure: Feasibility of recruiting 62 patients within 18 months
timeFrame: 18 months
measure: Safety
timeFrame: 3 years
measure: Efficacy
timeFrame: 5 years
measure: Efficacy
timeFrame: 24 months
Other outcomes:
Locations:
city: Bristol
country: United Kingdom
facility: Bristol Oncology and Haematology Centre
city: Cardiff
country: United Kingdom
facility: Valindre NHS
city: Coventry
country: United Kingdom
facility: University Hospitals Coventry and Warwickshire
city: Derby
country: United Kingdom
facility: Royal Derby Hospital
city: Leeds
country: United Kingdom
facility: St James's Hospital
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: London
country: United Kingdom
facility: St Mary's Hopsital
city: Manchester
country: United Kingdom
facility: The Christie
city: Oxford
country: United Kingdom
facility: Churchill Hospital
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
city: Swindon
country: United Kingdom
facility: The Great Western Hospital
Study officials:
References:
citation: Mukherjee S, Hurt C, Radhakrishna G, Gwynne S, Bateman A, Gollins S, Hawkins MA, Canham J, Grabsch HI, Falk S, Sharma RA, Ray R, Roy R, Cox C, Maynard N, Nixon L, Sebag-Montefiore DJ, Maughan T, Griffiths GO, Crosby TDL. Oxaliplatin/capecitabine or carboplatin/paclitaxel-based preoperative chemoradiation for resectable oesophageal adenocarcinoma (NeoSCOPE): Long-term results of a randomised controlled trial. Eur J Cancer. 2021 Aug;153:153-161. doi: 10.1016/j.ejca.2021.05.020. Epub 2021 Jun 20.
citation: Mukherjee S, Hurt CN, Gwynne S, Sebag-Montefiore D, Radhakrishna G, Gollins S, Hawkins M, Grabsch HI, Jones G, Falk S, Sharma R, Bateman A, Roy R, Ray R, Canham J, Griffiths G, Maughan T, Crosby T. NEOSCOPE: A randomised phase II study of induction chemotherapy followed by oxaliplatin/capecitabine or carboplatin/paclitaxel based pre-operative chemoradiation for resectable oesophageal adenocarcinoma. Eur J Cancer. 2017 Mar;74:38-46. doi: 10.1016/j.ejca.2016.11.031. Epub 2017 Feb 8.
citation: Mukherjee S, Hurt CN, Gwynne S, Bateman A, Gollins S, Radhakrishna G, Hawkins M, Canham J, Lewis W, Grabsch HI, Sharma RA, Wade W, Maggs R, Tranter B, Roberts A, Sebag-Montefiore D, Maughan T, Griffiths G, Crosby T. NEOSCOPE: a randomised Phase II study of induction chemotherapy followed by either oxaliplatin/capecitabine or paclitaxel/carboplatin based chemoradiation as pre-operative regimen for resectable oesophageal adenocarcinoma. BMC Cancer. 2015 Feb 12;15:48. doi: 10.1186/s12885-015-1062-y.