Condition category
Cancer
Date applied
27/04/2012
Date assigned
27/04/2012
Last edited
22/09/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Dr Matthew Goff

ORCID ID

Contact details

University of Oxford
Old Road Campus
Roosevelt Drive Headington
Oxford
OX3 7DQ
United Kingdom
-
octo-debioc@oncology.ox.ac.uk

Additional identifiers

EudraCT number

2011-003169-13

ClinicalTrials.gov number

Protocol/serial number

11855

Study information

Scientific title

A phase I dose-escalating and safety study of AZD8931 in combination with oxaliplatin and capecitabine chemotherapy in patients with oesophago-gastric adenocarcinoma

Acronym

Study hypothesis

AZD8931 blocks a growth pathway that is important in some cancers. In the escalation phase this trial will define the dose of AZD8931 that can safely be given with standard chemotherapy for oesophageal (gullet) cancer. We will then (in the expansion phase) compare the side effects of chemotherapy alone with those of AZD8931 with chemotherapy in 30 people with operable gullet cancer. This will to decide how to run future studies of AZD8931 with chemotherapy. This trial is supported by the Experimental Cancer Medicine Centres - Astrazeneca Combinations Alliance, and by the New Agents committee of Cancer Research UK. It is being run at hospitals in Oxford, Leicester and Belfast. Patients who go on the trial will need to undergo extra tests to check it is safe for them to take part, and to monitor them whilst on treatment.

Ethics approval

ref: 12/SC/0090

Study design

Both; Interventional; Design type: Treatment

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Upper gastro-intestinal cancer

Intervention

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 screening will receive AZD8931 monotherapy for three days (days -3 to -1) [20mg bd in cohort 1, 40 mg bd in cohort 2 and 60 mg bd in cohort 3]. Xelox chemotherapy will be added in on day 4 of AZD8931 treatment AZD8931 tablets will be taken orally, continuously, twice daily. Patients will receive oxaliplatin and capecitabine on day one of every cycle every 21 days. Oxaliplatin will be given at 130 mg/m2 IV in 250-500 ml of 5% glucose over 2 hours. Capecitabine 1250mg/m2/day will be given orally in two divided doses continuously from days 1-21 of each 3 week cycle. In this phase patients will receive a maximum of 8 cycles of daily AZD8931 in combination with Xelox. AZD8931 may be continued following cessation of the Xelox, providing the patient has no evidence of tumour progression and continues to tolerate treatment.

Dose Expansion - In the dose expansion phase of the trial, we propose a randomised component. Patients will receive two cycles of Xelox chemotherapy ± AZD8931 prior to undergoing an oesophago-gastrectomy. Twenty patients will receive Xelox and AZD8931 and 10 patients Xelox alone. The expectation is that this randomisation will allow us to assess any additive toxicity due to the combination of AZD8931 and Xelox over the toxicities associated with the Xelox backbone of chemotherapy alone. AZD8931 monotherapy will be used as maintenance therapy, in patients who were randomised to the combination and who have successful surgery, for a maximum of 12 months starting 6 to 12 weeks after surgery. Patients may therefore receive treatment for 58 weeks over a maximum 18 months period.

Maintenance Phase - To investigate the safety and feasibility of maintaining patients on AZD8931, to reduce the risk of recurrence, patients who have successful surgery will be allowed to continue AZD8931 if they were randomised to the combination, for a maximum of 12 months starting 6 to 12 weeks after surgery.

Intervention type

Drug

Phase

Phase I

Drug names

AZD8931, capecitabine, oxaliplatin

Primary outcome measures

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 outcome measures

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

Overall trial start date

30/04/2012

Overall trial end date

30/04/2017

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 54; UK Sample Size: 54

Participant 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.

Recruitment start date

30/04/2012

Recruitment end date

11/05/2016

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Belfast City Hospital
Lisburn Road
Belfast
BT9 7AB
United Kingdom

Trial participating centre

Leicester Royal Infirmary
Infirmary Square
Leicester
LE1 5WW
United Kingdom

Trial participating centre

Churchill Hospital
Old Road Headington
Oxford
OX3 7LE
United Kingdom

Trial participating centre

Bristol Haematology & Oncology Centre
Horfield Road
Bristol
BS2 8ED
United Kingdom

Trial participating centre

St. James University Hospital
Bexley Wing Beckett Street
Leeds
LS9 7TF
United Kingdom

Sponsor information

Organisation

University of Oxford (UK)

Sponsor details

Clinical Trials and Research Governance
Joint Research Office
Block 60
Churchill Hospital
Headington
OX3 7LJ
United Kingdom

Sponsor type

University/education

Website

http://www.ox.ac.uk/

Funders

Funder type

Industry

Funder name

AstraZeneca (UK)

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

United Kingdom

Funder name

Cancer Research UK

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

30/04/2018

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

15/08/2016: the following changes were made to the trial record: 1. The recruitment end date was changed from 30/04/2014 to 11/05/2016. 2. The overall trial end date was changed from 30/04/2014 to 30/04/2017. 3. The target number of participants was changed from 39 to 54.