None listed
Conditions
Interventions
Drug : Eligible patients will be stratified to HER2 IHC0 and HER2 IHC 1+/2+ according to the HER2 status and randomised to AZD8931 + paclitaxel and placebo + paclitaxel (1:1).
AZD8931 40mg or matched
Sponsors
AstraZeneca Korea
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of signed, written informed consent prior to any study specific procedures 2. Male or female aged 18 years or older (20 years or older in Japan) 3. Histological diagnosis of gastric adenocarcinoma (including adenocarcinoma of the gastro-oesophageal junction) 4. Patients must have radiologically confirmed progression following 1st line fluoropyrimidine/platinum based treatment for metastatic gastric cancer (the date of progression and start of first line treatment to be captured on the database) 5. Suitable for paclitaxel therapy 6. At least one lesion, not previously irradiated and not chosen for an optional fresh biopsy during the study screening period, that can be accurately measured at baseline as =10mm in longest diameter (except lymph nodes which must have short axis =15mm) by computed tomography (CT) or magnetic resonance imaging (MRI) and is suitable for accurate repeat assessment 7. World Health Organisation (WHO) performance status 0-1, minimum life expectancy of 12 weeks from proposed first dose date, no deterioration within 2 weeks of screening and first dose. Investigator has discretion to exclude rapidly progressive gastric cancer (such as those patients with rapid deterioration of performance status, requiring repeated drainage of ascites, patients with low or rapidly decreasing albumin or patients requiring feeding assistance with devices such as PEG) 8. Ineligible for trastuzumab treatment by local assessment. This should include IHC analysis to determine HER2 status with further testing by FISH/CISH for IHC 2+ patients. Eligible patients are those defined as; HER2 IHC 0, HER2 IHC 1+, or HER2 IHC 2+ (FISH negative) 9. Collection of the original archival diagnostic (or more recent archival) tumour sample for retrospective central HER2 assessment, followed by exploratory retrospective biomarker analysis. Both primary lesion and metastatic sites are acceptable. 10. Women should be using adequate contraceptive measures (see Appendix J), should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child bearing potential, or must have evidence of non-child bearing potential by fulfilling one of the following criteria at screening: For inclusion in the optional PGx sample collection: 11. Provision of informed consent for PGx sample collection For inclusion in the optional exploratory biomarker analysis: 12. Provision of informed consent for tumour sample collection
Exclusion criteria
Exclusion criteria: 1. Have received more than 1 prior chemotherapy regimen for metastatic gastric cancer. 2. Any prior taxane therapy 3. Any prior therapy with an inhibitor of ErbB1 (EGFR) or ErbB2 (HER2) 4. Inadequate bone marrow reserve as demonstrated by an absolute neutrophil count 14 days prior to the determination of the haemoglobin levels 7. Inadequate liver function defined as; serum bilirubin >2 x ULN, and ALT or AST >2.5 x ULN in the absence of noted liver metastases, and ALP >2.5 x ULN in the absence of noted liver metastases, or ALP, AST or ALT >5.0 x ULN if judged by the investigator to be related to liver metastases. 8. Resting ECG with measurable QTc(F) interval of >480 msec at 2 or more time points within a 24 hour period 9. Cardiac ejection fraction outside institutional range of normal or =50% (whichever is higher) as measured by echocardiogram(or MUGA) 10. Known uncontrolled or symptomatic angina, arrhythmias or congestive heart failure, evidence of transmural infarction on ECG, poorly controlled hypertension(systolic >180 mmHg or diastolic >100 mmHg), significant valvular disease or history of high risk dysrrhythmia (such as ventricular fibrillation or ventricular tachycardia [includes ventricular triplets]) 11. Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease 12. Active or uncontrolled systemic disease 13. History or repeated unexplained episodes of syncope/dizziness 14. Medical diagnosis of acne rosacea, psoriasis, severe atopic eczema 15. Concurrent second primary malignancy (except in situ carcinoma of the cervix). 16. Unresolved toxicity >CTCAE grade 2 (except alopecia) from previous anti-cancer therapy 17. Unable to discontinue medication with agents designated as having a risk of Torsades de Pointes due to QT prolongation. Guidance on medicines to avoid and on washout periods is given 18. Unable to discontinue any medication or herbal supplement with known moderate or potent inhibitory effect on CYP3A4, or potent inducing effects on CYP3A4. Such drugs must have been discontinued for an appropriate period prior to starting AZD8931. Guidance on medicines to avoid and on washout periods is given 19. Known hypersensitivity to AZD8931, its excipients, or drugs in its class (including oral tyrosine kinase inhibitors) 20. Involvement in the planning and/or conduct of the study 21. Receipt of investigational drug within 30 days or five half lives, whichever is longer, of the first dose of IP (AZD8931 or placebo) 22. Prior diagnosis of dry eye syndrome, eyelid or eyelash abnormalities 23. History or current evidence of any of the following: Any eye injury in the previous 3 months or a prior eye injury still associated with persistent or recurrent symptoms or impairment of vision, Or Corneal surgery, Or Orbital irradiation, Or Collagen vascular, chronic inflammatory or degenerative disease with eye involvement, Or Clinically significant ocular surface disease ie, diseases of the conjunctiva and cornea 24. History of maculopathy in patients with impaired visual acuity 25. Last dose of prior anticancer therapy received within 14 days (within 6 weeks for nitrosurea or mitomycin C) prior to the first dose of treatment with inves
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Progression Free Survival (PFS);Objective response rate (ORR);Percentage of patients without progressive disease;Overall survival (OS);safety and tolerability of AZD8931 plus paclitaxel;PK of AZD8931 and AZD8931 O-desmethyl metabolite | — |
Primary
| Measure | Time frame |
|---|---|
| Change in tumour size | — |
Countries
Korea, Republic of
Contacts
Public ContactSeock-Ah Im
Seoul National University Hospital
Outcome results
None listed