Upper gastro-intestinal cancer Cancer Malignant neoplasm of oesophagus
Conditions
Interventions
Dose Escalation ? In the dose escalation phase of the study patients with metastatic or inoperable disease will be recruited and no surgery is planned. Patients who successfully complete the screenin
Sponsors
University of Oxford (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 18 years 2. WHO performance status 01 3. Adequate respiratory and cardiac function 4. Able to give informed consent and be capable of cooperating with protocol 5. Haematological and biochemical indices within the ranges shown below: 5.1. Haemoglobin (Hb) =10g/dl 5.2. Neutrophils = 1500/µl 5.3. Platelet count = 100.000/µl 5.4. AST or ALT = 3 ULN, alkaline phosphatase = 2x ULN 5.5. Serum Bilirubin = 1.5 ULN 5.6. Creatinine Clearance = 50ml/min 6. Able to swallow oral medication 7. Women of child bearing potential must use an acceptable method of contraception during the study, and have a negative pregnancy test 8. Male patients must use a barrier method of contraception - male condom (female condom or diaphragm are not acceptable) during the study. 9. For the dose escalation phase patients with locally advanced or metastatic oesophageal or gastro-oesophageal junction adenocarcinoma (including Siewert type I and II). In the dose expansion phase 10. Histologically confirmed carcinoma of the oesophagus and gastrooesophageal junction [GOJ] 11. Siewert Type I and II Operable disease: any combination T13 / N01 [BUT EXCLUDES T1N0] 12. T4 involvement of mediastinal pleura and diaphragmatic crus where the MDT consider this resectable. 13. Deemed suitable for neoadjuvant chemotherapy by regional upper gastrointestinal Multi-Disciplinary Team; 14. Target Gender: Male & Female 15. Lower Age Limit 18 years
Exclusion criteria
Exclusion criteria: 1. Previous chemotherapy for oesophagogastric adenocarcinoma 2. Siewert Type III GOJ tumours and gastric cancer 3. Squamous cell pathology 4. Uncontrolled angina, myocardial infarction within 6 months, heart failure or impaired LV function on echocardiogram/MUGA, uncontrolled arrhythmias. 5. History of interstitial lung disease 6. Known peripheral neuropathy >Grade 1 7. Other experimental treatment = 4 weeks prior to this study (including chemotherapy and immunotherapy) 8. Known or expected dihydropyridime dehydrogenase deficiency 9. Resting ECG with QTc >480msec at 2 or more time points within a 24h period 10. Requirement for medication known to inhibit or induce CYP3A4 or 2D6, or medication known to prolong QT interval 11. History of other malignancy less than 5 years before the diagnosis of oesophageal cancer, EXCLUDING the following: Non-melanoma skin cancer, in situ carcinoma of the cervix treated surgically with curative intent, other malignant tumours that have been treated curatively and patient is deemed disease-free 12. Active infections (including chronic hepatitis type B or C and HIV infection if status known), severe immunologic defect, compromised bone marrow function 13. Prior diagnosis of dry eye syndrome or eyelid/eyelash abnormalities. History of eye injury, corneal surgery, orbital irradiation, collagen vascular, chronic inflammatory or denegerative disease with eye involvement, clinically significant ocular surface disease 14. Known hypersensitivity to any component of chemotherapy 15. Pregnancy, inadequate or unreliable contraceptive measures during participation in the trial; breast feeding. 16. Other psychological, social or medical condition, physical examination finding or a laboratory abnormality that the Investigator considers would make the patient a poor trial candidate or could interfere with protocol compliance or the interpretation of trial results.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Assessment of efficacy for the combination of AZD8931 + Xelox in patients with operable OG carcinoma 2. 6-month progression-free survival rate 3. R0 resection rate 4. Progression free and overall survival | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Pharmacokinetics (PK) of AZD8931 when co-administered with Xelox 2. Serum AZD8931 concentration 3. Tolerability of post-operative maintenance therapy with AZD8931 4. Adverse events using CTCAE v4.03 5. Number of patients starting maintenance therapy | — |
Countries
England, Northern Ireland, United Kingdom
Outcome results
None listed