Title

DEBIOC

Chief Investigator: 
Anne Thomas

Sponsor: University of Oxford
EudraCT number: 2011-003169-13

A Phase I dose-escalating and safety study of AZD8931 in combination with Oxaliplatin and Capecitabine chemotherapy in patients with Oesophago-gastric adenocarcinoma

Further information about this trial can be found on the CRUK website.

Objectives

  • To establish maximum tolerated dose of AZD8931 in combination with Xelox chemotherapy and define the safety of the combination and safety of post-operative AZD8931 maintenance therapy.
  • Also to assess early efficacy data as determined by progression free survival (PFS) at 6 months and complete resection rate (R0). Pharmacodynamic biomarkers including blood, tissue and imaging will also be investigated to help select a patient population for further studies.

Study Status:

Open to recruitment

Active sites: 3

Leicester Royal Infirmary

Churchill Hospital Oxford
Belfast City Hospital
St James' Leeds
Bristol Haemotology & Oncology Centre

Target recruitment: 54

Current recruitment: 28 (April 2015)

The study has completed recruitment to the escalation phase (24 patients) and the maximum tolerated dose for AZD8931 in combination with Xelox. The study re-started recruitment for the expansion phase in January 2015.
 

Inclusion Criteria

All patients

  1. Age ≥ 18 years
  2. WHO performance status 0-1
  3. Adequate respiratory and cardiac function
  4. Able to give informed consent and be capable of co-operating with protocol
  5. Haematological and biochemical indices within the ranges shown below:
  6. Haemoglobin (Hb) ≥10g/dl,
  7. Neutrophils≥ 2000/µl,
  8. Platelet count ≥ 100.000/µl,
  9. AST or ALT ≤ 3 ULN, alkaline phosphatase ≤ 2x ULN,
  10. Serum Bilirubin ≤ 1.5 ULN,
  11. Creatinine Clearance ≥ 50ml/min (Calculated by Cockcroft Gault equation, or by EDTA)(Appendix 3)
  12. Able to swallow oral medication
  13.  Male patients must use a barrier method of contraception (female condom or diaphragm are not acceptable) during the study and after cessation of therapy for 6 months.

Dose escalation phase only

  • Patients with locally advanced or metastatic gastro-oesophageal adenocarcinoma, i.e. inoperable
  • Women of child bearing potential must use an acceptable method of contraception during the study and after cessation of therapy for 4 months, and have a negative pregnancy test

Dose expansion phase only

  • Histologically confirmed carcinoma of the oesophagus and gastro-oesophageal junction [GOJ] Siewert Type I and II
  • Operable disease: any combination T1-3 / N0-1 [BUT EXCLUDES T1N0]; T4 involvement of mediastinal pleura and diaphragmatic crus where the MDT consider this resectable
  • Deemed suitable for neo-adjuvant chemotherapy by regional upper GI MDT
  • Women Not of Childbearing Potential i.e. women who are postmenopausal or permanently sterilised (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy). Pregnancy test must be done for women who have been post-menopausal for less than 2 years.

Dose Maintenance phase

  • Patients who have successful surgery
  • Patients who received AZD8931 Treatment in the expansion phase

Exclusion Crtieria

  1. Previous chemotherapy for oesophago-gastric adenocarcinoma
  2. Squamous cell pathology
  3. Uncontrolled angina, myocardial infarction within 6 months, heart failure or impaired LV function on echocardiogram/MUGA, uncontrolled arrhythmias
  4. History of interstitial lung disease
  5. Known peripheral neuropathy >Grade 1
  6. Other experimental treatment ≤ 4 weeks prior to this study (including chemotherapy and immunotherapy)
  7. Known or expected dihydropyridime dehydrogenase deficiency
  8. Resting ECG with QTc >480msec at 2 or more time points within a 24h period
  9. Requirement for medication known to inhibit or induce CYP3A4 or 2D6, or medication known to prolong QT interval (see appendix 4).
  10. 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
  11. Active infections (including chronic hepatitis type B or C and HIV infection if status known), severe immunologic defect, compromised bone marrow function
  12. Prior diagnosis of dry eye syndrome or eye-lid/eye-lash abnormalities.  History of eye injury, corneal surgery, orbital irradiation, collagen vascular, chronic inflammatory or denegerative disease with eye involvement, clinically significant ocular surface disease
  13. Known hypersensitivity to any component of chemotherapy
  14. Pregnancy, inadequate or unreliable contraceptive measures during participation in the trial; breast feeding.
  15. 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.

Dose expansion phase and dose maintenance phase only

  • Siewert Type III GOJ tumours and gastric cancer
  • Women of child bearing potential i.e. Any female who has experienced menarche and does not meet the criteria for “Women Not of Childbearing Potential”

Data Submission

Data submission for this trial is via electronic submission of data in OpenClinica.

OpenClinica Training

OpenClinica is the world's leading open source clinical trial software for electronic data capture and clinical data management. 

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