Clinical Trials List
Protocol NumberD0102C00006
2012-03-01 - 2014-06-30
Phase II
Terminated4
Study ended1
ICD-10C16.9
Malignant neoplasm of stomach, unspecified
ICD-10C7A.092
Malignant carcinoid tumor of the stomach
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9151.9
Malignant neoplasm of stomach, unspecified
A Phase IIa Multi-centre Randomised Double-Blind Placebo-controlled Study to Assess the Efficacy, Safety and Pharmacokinetics of AZD8931 in Combination with Paclitaxel versus Paclitaxel alone in Patients with Metastatic, Gastric or Gastro-oesophageal Junction, Cancer who progress following First Line Therapy and are Ineligible for Treatment with trastuzumab by HER2 Status (SAGE)
-
Trial Applicant
-
Sponsor
AstraZeneca
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Chih-Hung Hsu Division of Hematology & Oncology
- 林育麟 Division of Hematology & Oncology
- SHIH-HUNG YANG Division of Hematology & Oncology
- Ann-Lii Cheng Division of Hematology & Oncology
- SUNG-HSIN KUO Division of Hematology & Oncology
- 張端瑩 Division of Hematology & Oncology
- Chia-Chi Lin Division of Hematology & Oncology
- SHIH-HUNG YANG Division of Hematology & Oncology
- Chiun Hsu Division of Hematology & Oncology
- Ying-Chun Shen Division of Hematology & Oncology
- TA-CHEN HUANG Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Wen-Chi Chou Division of Hematology & Oncology
- Huei-Keng Ma Division of Ophthalmology
- Tsai-Sheng Yang Division of Hematology & Oncology
- Ming-Mo Hou Division of Hematology & Oncology
- Hung-Chih Hsu Division of Hematology & Oncology
- 曾振輝 Division of Radiology
- Wen-Chi Shen Division of Hematology & Oncology
- Chi-Ting Liau Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Yu-Min Liao Division of Hematology & Oncology
- Chang-Fang Chiu Division of Hematology & Oncology
- Ching Yun Hsieh Division of Hematology & Oncology
Condition/Disease
Gastric or Gastro-oesophageal Junction Cancer
Objectives
To assess the relative efficacy of AZD8931 plus paclitaxel compared with paclitaxel alone by
comparison of the change in tumour size at 8 weeks.
The secondary objectives of the study are:
• 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.
Test Drug
AZD8931
Active Ingredient
AZD8931
Dosage Form
tablet
Dosage
40
Endpoints
All randomised patients will be included in the efficacy analysis set to assess PFS, OS and
percentage of patients without progression at 8 weeks based on randomised treatment. This is
referred to as the ITT analysis set. If a patient does not receive any treatment or does not
receive their randomised treatment they will be included in the ITT analysis set based on their
randomised treatment.
For change in tumour size at 8 weeks (primary endpoint) and ORR, all patients in the ITT
population who have measurable disease at baseline per RECIST 1.1 criteria will be included
in the analysis.
percentage of patients without progression at 8 weeks based on randomised treatment. This is
referred to as the ITT analysis set. If a patient does not receive any treatment or does not
receive their randomised treatment they will be included in the ITT analysis set based on their
randomised treatment.
For change in tumour size at 8 weeks (primary endpoint) and ORR, all patients in the ITT
population who have measurable disease at baseline per RECIST 1.1 criteria will be included
in the analysis.
Inclution Criteria
For inclusion in the study, patients must fulfil all of the following 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 when
considered part of local practice. Eligible patients are those defined as; HER2 IHC
0, HER2 IHC 1+, or HER2 IHC 2+ (FISH –ve)
9. Collection of an archival diagnostic (or more recent) tumour sample for
retrospective central HER2 assessment. 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 more than 50 years and amenorrhoeic for at least 12 months
following cessation of all exogenous hormonal treatments
− Aged under 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 exploratory biomarker analysis:
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.
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 when
considered part of local practice. Eligible patients are those defined as; HER2 IHC
0, HER2 IHC 1+, or HER2 IHC 2+ (FISH –ve)
9. Collection of an archival diagnostic (or more recent) tumour sample for
retrospective central HER2 assessment. 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 more than 50 years and amenorrhoeic for at least 12 months
following cessation of all exogenous hormonal treatments
− Aged under 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 exploratory biomarker analysis:
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.
Exclusion Criteria
Patients must not enter the study if any of the following exclusion criteria are fulfilled
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 (EGFR) or ErbB2 (HER2)
(eg, lapatinib)
4. Inadequate bone marrow reserve as demonstrated by an absolute neutrophil count
<1.5 x 109/L or platelet count <100 x 109/L
5. Moderate or severe renal impairment. If creatinine is >1x ULN, creatinine clearance
or glomerular filtration rate (GFR) must be calculated using the Cockcroft-Gault or
Modification of Diet in Renal Disease formula. Creatinine clearance or GFR is <50
mL/min
6. Haemoglobin ≤9 g/dL (5.59 mmol/L), any blood transfusion must be >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. Elevated ALP is not exclusionary if due to the
presence of bone metastasis and liver function is otherwise considered
adequate in the investigator’s judgment.
8. Resting ECG with measurable QTc(F) interval of >480 msec at 2 or more time
points within a 24 hour period (see section 6.4.9.1 )
9. Cardiac ejection fraction outside institutional range of normal or ≤50% (whichever
is higher) as measured by echocardiogram (or multiple uptake gated acquisition
scan (MUGA) if an echocardiogram cannot be performed or is inconclusive)
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. Guidance on medicines to avoid and
on washout periods is given in Appendix G to this protocol
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, its excipients, or drugs in its class (including
oral tyrosine kinase inhibitors)
20. Involvement in the planning and/or conduct of the study (applies to both AZ staff
and/or staff at the study site)
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
− 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 (including atopic keratoconjunctivitis, StevensJohnson syndrome, ocular cicatricial pemphigoid or chemical burns,
herpes simplex or herpes zoster virus eye disease)
24. History of maculopathy in patients with impaired visual acuity. (Impaired visual
acuity is defined as best corrected near visual acuity <0.4 or best corrected distance
visual acuity (including with pinhole) <0.7) Note: patients with cataracts are
allowed. No eye symptoms must be present on Day 1 of AZD8931 dosing
25. Last dose of prior anticancer therapy (chemotherapy, radiation therapy, surgery,
immunotherapy, targeted therapy, biologic therapy, or tumour embolisation)
received within 14 days (within 6 weeks for nitrosurea or mitomycin C) prior to the
first dose of treatment with investigational product (IP) (AZD8931 or placebo). If
sufficient wash-out time has not occurred due to schedule or PK properties, a longer
wash-out period will be required, as agreed by AZ and the investigator / delegate
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 (EGFR) or ErbB2 (HER2)
(eg, lapatinib)
4. Inadequate bone marrow reserve as demonstrated by an absolute neutrophil count
<1.5 x 109/L or platelet count <100 x 109/L
5. Moderate or severe renal impairment. If creatinine is >1x ULN, creatinine clearance
or glomerular filtration rate (GFR) must be calculated using the Cockcroft-Gault or
Modification of Diet in Renal Disease formula. Creatinine clearance or GFR is <50
mL/min
6. Haemoglobin ≤9 g/dL (5.59 mmol/L), any blood transfusion must be >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. Elevated ALP is not exclusionary if due to the
presence of bone metastasis and liver function is otherwise considered
adequate in the investigator’s judgment.
8. Resting ECG with measurable QTc(F) interval of >480 msec at 2 or more time
points within a 24 hour period (see section 6.4.9.1 )
9. Cardiac ejection fraction outside institutional range of normal or ≤50% (whichever
is higher) as measured by echocardiogram (or multiple uptake gated acquisition
scan (MUGA) if an echocardiogram cannot be performed or is inconclusive)
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. Guidance on medicines to avoid and
on washout periods is given in Appendix G to this protocol
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, its excipients, or drugs in its class (including
oral tyrosine kinase inhibitors)
20. Involvement in the planning and/or conduct of the study (applies to both AZ staff
and/or staff at the study site)
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
− 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 (including atopic keratoconjunctivitis, StevensJohnson syndrome, ocular cicatricial pemphigoid or chemical burns,
herpes simplex or herpes zoster virus eye disease)
24. History of maculopathy in patients with impaired visual acuity. (Impaired visual
acuity is defined as best corrected near visual acuity <0.4 or best corrected distance
visual acuity (including with pinhole) <0.7) Note: patients with cataracts are
allowed. No eye symptoms must be present on Day 1 of AZD8931 dosing
25. Last dose of prior anticancer therapy (chemotherapy, radiation therapy, surgery,
immunotherapy, targeted therapy, biologic therapy, or tumour embolisation)
received within 14 days (within 6 weeks for nitrosurea or mitomycin C) prior to the
first dose of treatment with investigational product (IP) (AZD8931 or placebo). If
sufficient wash-out time has not occurred due to schedule or PK properties, a longer
wash-out period will be required, as agreed by AZ and the investigator / delegate
The Estimated Number of Participants
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Taiwan
15 participants
-
Global
60 participants
