A Feasibility Study of Chemo-radiotherapy to Treat Operable Oesophageal Cancer

Phase 2

• Conditions: Oesophageal Cancer
• Interventions: Drug: Oxaliplatin; Drug: Capecitabine; Radiation: Radiotherapy; Drug: Carboplatin; Drug: Paclitaxel; Procedure: Surgery

• Registration Number: NCT01843829
• Lead Sponsor: Lisette Nixon

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-03-07
• Study First Submitted QC: 2013-04-30
• Study First Posted: 2013-05-01
• Study Start: 2013-10
• Status Verified: 2014-03
• Last Update Submitted: 2014-03-21
• Last Update Posted: 2014-03-24
• Primary Completion: 2015-05
• Study Completion: 2016-05

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 85

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Oxaliplatin and Capecitabine Arm	Radiotherapy	2 cycles OxCap: Oxaliplatin 130mg/m2 Day 1 (IV infusion) Capecitabine 625mg/m2 bd Day 1- 21 (oral) then CRT: Oxaliplatin 85mg/m2 Days 1, 15, 29 (IV infusion); Capecitabine 625mg/m2 bd (oral) only on days when receiving RT XRT: 45 Gy in 25 fractions\* then surgery. All drugs will be sourced from local stock
Carboplatin and Paclitaxel Arm	Surgery	2 cycles OxCap: Oxaliplatin 130mg/m2 Day 1 (IV infusion) Capecitabine 625mg/m2 bd Day 1- 21 (oral) then CRT: Paclitaxel 50mg/m2 Days 1,8,15,22,29 (IV infusion); Carboplatin AUC 2 Days 1,8,15,22,29 (IV infusion) XRT: 45 Gy in 25 fractions then surgery. All drugs will be sourced from local stock
Carboplatin and Paclitaxel Arm	Radiotherapy	2 cycles OxCap: Oxaliplatin 130mg/m2 Day 1 (IV infusion) Capecitabine 625mg/m2 bd Day 1- 21 (oral) then CRT: Paclitaxel 50mg/m2 Days 1,8,15,22,29 (IV infusion); Carboplatin AUC 2 Days 1,8,15,22,29 (IV infusion) XRT: 45 Gy in 25 fractions then surgery. All drugs will be sourced from local stock
Oxaliplatin and Capecitabine Arm	Surgery	2 cycles OxCap: Oxaliplatin 130mg/m2 Day 1 (IV infusion) Capecitabine 625mg/m2 bd Day 1- 21 (oral) then CRT: Oxaliplatin 85mg/m2 Days 1, 15, 29 (IV infusion); Capecitabine 625mg/m2 bd (oral) only on days when receiving RT XRT: 45 Gy in 25 fractions\* then surgery. All drugs will be sourced from local stock
Carboplatin and Paclitaxel Arm	Oxaliplatin	2 cycles OxCap: Oxaliplatin 130mg/m2 Day 1 (IV infusion) Capecitabine 625mg/m2 bd Day 1- 21 (oral) then CRT: Paclitaxel 50mg/m2 Days 1,8,15,22,29 (IV infusion); Carboplatin AUC 2 Days 1,8,15,22,29 (IV infusion) XRT: 45 Gy in 25 fractions then surgery. All drugs will be sourced from local stock
Carboplatin and Paclitaxel Arm	Paclitaxel	2 cycles OxCap: Oxaliplatin 130mg/m2 Day 1 (IV infusion) Capecitabine 625mg/m2 bd Day 1- 21 (oral) then CRT: Paclitaxel 50mg/m2 Days 1,8,15,22,29 (IV infusion); Carboplatin AUC 2 Days 1,8,15,22,29 (IV infusion) XRT: 45 Gy in 25 fractions then surgery. All drugs will be sourced from local stock
Carboplatin and Paclitaxel Arm	Capecitabine	2 cycles OxCap: Oxaliplatin 130mg/m2 Day 1 (IV infusion) Capecitabine 625mg/m2 bd Day 1- 21 (oral) then CRT: Paclitaxel 50mg/m2 Days 1,8,15,22,29 (IV infusion); Carboplatin AUC 2 Days 1,8,15,22,29 (IV infusion) XRT: 45 Gy in 25 fractions then surgery. All drugs will be sourced from local stock
Carboplatin and Paclitaxel Arm	Carboplatin	2 cycles OxCap: Oxaliplatin 130mg/m2 Day 1 (IV infusion) Capecitabine 625mg/m2 bd Day 1- 21 (oral) then CRT: Paclitaxel 50mg/m2 Days 1,8,15,22,29 (IV infusion); Carboplatin AUC 2 Days 1,8,15,22,29 (IV infusion) XRT: 45 Gy in 25 fractions then surgery. All drugs will be sourced from local stock
Oxaliplatin and Capecitabine Arm	Oxaliplatin	2 cycles OxCap: Oxaliplatin 130mg/m2 Day 1 (IV infusion) Capecitabine 625mg/m2 bd Day 1- 21 (oral) then CRT: Oxaliplatin 85mg/m2 Days 1, 15, 29 (IV infusion); Capecitabine 625mg/m2 bd (oral) only on days when receiving RT XRT: 45 Gy in 25 fractions\* then surgery. All drugs will be sourced from local stock
Oxaliplatin and Capecitabine Arm	Capecitabine	2 cycles OxCap: Oxaliplatin 130mg/m2 Day 1 (IV infusion) Capecitabine 625mg/m2 bd Day 1- 21 (oral) then CRT: Oxaliplatin 85mg/m2 Days 1, 15, 29 (IV infusion); Capecitabine 625mg/m2 bd (oral) only on days when receiving RT XRT: 45 Gy in 25 fractions\* then surgery. All drugs will be sourced from local stock

Primary Outcome Measures

Name	Time	Method
Efficacy	24 months	The efficacy of the trial treatment will be assessed by conducting analysis on the resected tumour specimen of participants undergoing surgery. This will be achieved by looking at the pathological complete response rate (pCR).

Secondary Outcome Measures

Name	Time	Method
Feasibility of recruiting 62 patients within 18 months	18 months	Feasibility of recruiting to a pre-operative chemoradiotherapy trial in the UK will be determined by recruitment within 18 months.
Safety	3 years	The trial safety will be assessed by looking at the toxicity. Toxicities during treatment and at 6 and 12 months post-surgery will be recorded using the CTCAE version 4. SAEs will be collected in real time. The morbidity/mortality rate post surgery will also be assessed.
Efficacy	24 months	The CRM (circumferential resection margin) which is a measurement of how successful the surgery was in removing all traces of tumour, will be assessed.

Trial Locations

Locations (12)

University Hospitals Coventry and Warwickshire; 🇬🇧 Coventry, United Kingdom

Bristol Oncology and Haematology Centre; 🇬🇧 Bristol, United Kingdom

Valindre NHS; 🇬🇧 Cardiff, United Kingdom

Royal Derby Hospital; 🇬🇧 Derby, United Kingdom

St James's Hospital; 🇬🇧 Leeds, United Kingdom

Leicester Royal Infirmary; 🇬🇧 Leicester, United Kingdom

St Mary's Hopsital; 🇬🇧 London, United Kingdom

The Christie; 🇬🇧 Manchester, United Kingdom

Churchill Hospital; 🇬🇧 Oxford, United Kingdom

Weston Park Hospital; 🇬🇧 Sheffield, United Kingdom

Southampton General Hospital; 🇬🇧 Southampton, United Kingdom

The Great Western Hospital; 🇬🇧 Swindon, United Kingdom