Protocol title: A Randomised Phase II Trial of Pre-operative cisplatin, 5 fluorouracil and docetaxel ± Radiotherapy based on poor early response to standard chemotherapy for resectable adenocarcinoma of the oesophagus and/or OG Junction.
Study Chairs: Prof. Andrew Barbour and A/Prof. Euan Walpole (Princess Alexandra Hospital, Woolloongabba QLD)
Associate Oncology Program Manager: Cheryl Friend
Trial Coordinator: Tina Van Tonder
Contact Email: firstname.lastname@example.org
Detailed information available on: Australian and New Zealand Clinical Trials Registry — DOCTOR
Grants Awarded: NHMRC Grant: $387, 000 (2011)
Funds were received by the AGITG in 2014 ($35,250) for site payments and insurance costs. This income and associated expenditure are included in the 2014 Income Statement.
This study represents a paradigm shift in the administration of pre-operative therapy for oesophageal adenocarcinoma (OAC). This will be the first study to focus on metabolic non-reponders to pre-operative therapy in so far as the management of this group will be changed to a different therapy to try to improve response and potentially survival. This study will be the first to use the combination of DCF +/- RT in non-responding patients with OAC generating novel safety and efficacy data. It will determine whether changing therapy can salvage a response and provide valuable data regarding the potential to individualise therapy related to the tumour characteristics — so called ”tailored therapy”.
Finally the routine pre-treatment tumour and blood banking will give our group a unique opportunity to search for OAC biomarkers that may be indicators for FDG-PET response, response to the regimens used and possibly assessment of survival. The primary aim is to assess whether changing the pre-operative therapy regimen to DCF +/- RT after the first cycle of chemotherapy for early metabolic non-responders to CF will induce a histological response. Study endpoints include: major histological response (<10% residual viable tumour) and secondary endpoints of PFS, OS, toxicity, HRQoL and feasibility of response-based therapy. In addition banking of tumour tissue and blood before and after treatment for future molecular analyses investigating biomarkers of response will be undertaken.
Over the last 30 years, the incidence of OAC in Australia has increased more than any other cancer. Surgery forms the mainstay of curative treatment, however survival remains poor. Preoperative chemotherapy (CTX) with or without concurrent radiotherapy (CRT) have resulted in modest improvements in outcome. Patients who demonstrate a histological response in the resected specimen following pre-operative therapy (CTX or CRT) have consistently better survival than non-responders. Recent data suggests that a reduction in the level of tumour activity seen on a PET scan performed 14 days after the start of CTX compared with a baseline PET scan (”early metabolic response”), is predictive of a histological response and improved survival. Increasing the proportion of responders to pre-operative therapy remains one of the major challenges facing patients with localised OAC. We believe it is time to undertake the first clinical trial aimed at improving outcomes for early metabolic non-responders by changing their therapy after the first cycle of standard CTX to include docetaxel +/- radiotherapy.
This is a randomized Phase II study for patients that are PET-non-responders to induction chemotherapy. Patients will be randomised equally to the two treatment groups. Additionally; information on a third group of patients who respond to induction chemotherapy will be collected to help inform future studies.
A sample size of 30 patients per arm will have 80% power with 95% confidence to exclude an uninteresting histological response rate of 5% in favour of a 20% response rate in each arm. A formal comparison for response rates between the two randomised groups is not planned. This study will have 48 months accrual and 36 month follow up.
To view the study schema click here.