Metastatic, Gastric or Gastro-oesophageal Junction Cancer MedDRA version: 14.1 Level: LLT Classification code 10071114 Term: Metastatic gastric adenocarcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: AZD8931 film-coated tablet 20mg
Product Code: AZD8931
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: not available
CAS Number: 1196531-39-1
Current Sponsor code: AZD8931dif
Sponsors
AstraZeneca AB
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 and 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 a mandatory fresh tumour 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 i.e. the tumour site chosen for mandatory biopsy will not be deemed measurable and will be classed as a non-target lesion at baseline RECIST 1.1 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 –ve) 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: · Post menopausal defined as: - Aged = 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments - Aged <50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments and with luteinising hormone and follicular stimulating hormone levels in the post menopausal range · Documentation of irreversible surgical sterilization by hysterectomy, and/or bilateral oophorectomy and/or bilateral salpingectomy but excludes bilateral tubal ligation For inclusion in the optional PGx sample collection: 11. Provision of informed consent for PGx sample collection For inclusion in the optional fresh tumour biopsy upon RECIST 1.1 defined progression: 12. Provision of informed consent for tumour sample collection If a patient declines to participate in the optional components of the study (PGx or additional tumor sample collection) there will be no penalty or loss of benefit to the patients. The patient will not be excluded from other aspects of the study to which they have consented. 13. Patien
Exclusion criteria
Exclusion criteria: 1.Have received more than 1 prior chemotherapy regimen for metastatic gastric cancer. (chemotherapy as adjuvant treatment is permitted). 2.Any prior taxane therapy (at any time from diagnosis of gastric cancer) 3.Any prior therapy with an inhibitor of ErbB1 or ErbB2 (eg, lapatinib) 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 in protocol; 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 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 which in the investigator’s / delegate’s opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol 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). Patients with a prior cancer are eligible if they are disease-free with no evidence of recurrence or relapse in the past 5 years 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. 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 in Appendix G to this protocol 19.Known hypersensitivity to AZD8931 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 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 -Corneal surgery (laser refractive surgery performed more than 3 months prior to the start of the study is allowed and should be recorded in surgical history) -Orbital irradiation -Collagen vascular, chronic inflammatory or degenerative disease with eye involvement (eg, rheumatoid, Sjögren’s syndrome, systemic lupus erythematosus ) -Clinically significant ocular surface disease ie, diseases of the conjunctiva and cornea (incl
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the relative efficacy of AZD8931 plus paclitaxel compared with paclitaxel alone by comparison of the change in tumour size at 8 weeks;Secondary Objective: · To assess the relative efficacy of AZD8931 plus paclitaxel compared with paclitaxel alone by assessment of progression-free survival (PFS) · To investigate the efficacy of AZD8931 plus paclitaxel compared with paclitaxel alone by assessment of objective response rate (ORR) · To assess the efficacy of AZD8931 plus paclitaxel compared with paclitaxel alone by assessment of the percentage of patients without progressive disease (i.e. patients with CR, PR or SD) at 8 weeks · To assess the efficacy of AZD8931 plus paclitaxel compared with paclitaxel alone by assessment of overall survival (OS) · To compare and assess the safety and tolerability of AZD8931 plus paclitaxel compared with paclitaxel alone · To investigate the pharmacokinetics (PK) of AZD8931 and AZD8931 O-desmethyl metabolite in a metastatic, gastric or gastro-oesophageal junction, cancer patient population. ;Primary end point(s): Efficacy- Change in tumour size at 8 weeks ;Timepoint(s) of evaluation of this end point: Change in tumour size at 8 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy- -Progression Free Survival (PFS) -Overall survival (OS) -Objective response rate (ORR) -Percentage of patients without progressive disease at 8 weeks (i.e. patients with CR, PR or SD) Safety- Adverse Events - Deaths - Laboratory findings (clinical chemistry, haematology, urinalysis) - Vital signs - Physical Examination - Ophthalmic assessments Pharmacokinetic - Plasma concentrations of AZD8931 and AZD8931 O-desmethyl metabolite - Pharmacokinetic parameters including (but not restricted to): AZD8931: AUCss, Css,max, Css,min,tssmax, CLss/F and tlast AZD8931 O-desmethyl metabolite : AUC0-t, Cmax, tmax and AUC0-t metabolite:parent ratio - Cardiac assessments (ECG, ECHO/MUGA) ;Timepoint(s) of evaluation of this end point: Assessment made during trial | — |
Countries
China, Italy, Japan, Korea, Republic of, Spain, Taiwan, United Kingdom
Contacts
Public ContactInformation Centre
AstraZeneca AB
Outcome results
None listed