The purpose of this study is to determine the Maximum Tolerated Dose (MTD) of olaparib in combination with radical radiotherapy in patients with oesophageal cancer who are unsuitable for platinum containing chemotherapy.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
36
25mg tablets, oral. Commenced 3 days prior to radiotherapy and continuing until the last day of radiotherapy (36 days in total).
Radiotherapy to the oesophageal carcinoma. For patients receiving olaparib this is delivered as 50Gy in 25 daily fractions for 5 weeks (Monday-Friday only). For patients in the comparator arm (RT only) other total doses/ fractionation are permitted, according to local policy/ best standard care.
The Christie NHS Foundation Trust
Manchester, United Kingdom
NOT_YET_RECRUITINGSouthampton General Hospital
Southampton, United Kingdom
RECRUITINGMaximum Tolerated Dose (MTD) of olaparib in combination with radical radiotherapy in patients with oesophageal cancer
MTD will be determined by the number of patients experiencing dose limiting toxicities (DLTs) in each treatment cohort, using a 3+3 dose escalation schedule. A DLT is determined as grade 4 oesophagitis or dysphagia, or any other grade 3 toxicity. DLTs will be assessed weekly during treatment (day -3 to week 5), 10-14 days after completing treatment, weekly for a further 3 weeks and 3 months after completing treatment.
Time frame: 3 months post treatment
Overall toxicity profile of treatment (NCRI Common Toxicity Criteria for Adverse Effects V3)
Toxicity of treatment will be assessed via collection of adverse events, categorised by the NCRI Common Toxicity Criteria for Adverse Effects (CTCAE) V3. Adverse event data will be collected continuously from screening, with patients seen weekly during their treatment, 10-14 days after treatment completion, weekly for 3 further weeks, 3 monthly until 1 year then 6 monthly until 3 years.
Time frame: Assessed at all study visits, up to 3 years post treatment.
Olaparib compliance
Time frame: At completion of olaparib treatment (end of week 5)
Radiotherapy (RT) compliance
Time frame: At completion of RT treatment (end of week 5)
Local and overall treatment failure rate
This is defined as residual disease pathologically on endoscopic assessment \& biopsy or progressive disease on CT scan of thorax and abdomen.
Time frame: 3 months
Exploration of blood and tissue borne pharmacodynamic markers to establish the biological efficacy of the addition of Olaparib to radiotherapy.
* Endoscopic biopsy sample taken for analysis at screening \& 3 months post treatment * Translational research blood samples taken at screening, weekly during treatment, at end of treatment visit \& 3 months after treatment * Skin biopsy samples taken from within \& outside irradiated field at week 4
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Time frame: Up to 3 months post treatment