Clinical Trials List
Protocol NumberD2610C00004
2011-12-01 - 2016-07-31
Phase II
Terminated6
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 Randomised Open-Label Phase IIa Study to Assess the Efficacy and Safety of AZD4547 Monotherapy versus Paclitaxel in Patients with Advanced Gastric or Gastro-oesophageal Junction Cancer with FGFR2 Polysomy or Gene Amplification (Shine study)
-
Trial Applicant
-
Sponsor
AstraZeneca
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Chia-Chi Lin Division of Hematology & Oncology
- Yu-Chieh Tsai Division of Hematology & Oncology
- Chiun Hsu Division of Hematology & Oncology
- Ying-Chun Shen Division of Hematology & Oncology
- 張端瑩 Division of Hematology & Oncology
- 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
- SHIH-HUNG YANG Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 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
- 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
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Chung-Pin Li Digestive System Department
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Yu-Min Liao Division of Hematology & Oncology
- Chang-Fang Chiu Division of Hematology & Oncology
- Ching Yun Hsieh Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Advanced Gastric or Gastro-oesophageal Junction Cancer
Objectives
The primary objective of the study is:
To assess the relative efficacy of AZD4547 compared with paclitaxel by comparison of the
change in tumour size at 8 weeks in all randomised patients and also in the patients with
tumours that have FGFR2 amplification (FISH score 6) alone.
The secondary objectives of the study are:
• To assess the relative efficacy of AZD4547 compared with paclitaxel by assessment
of progression-free survival (PFS) in all randomised patients and also in the patients
with tumours that have FGFR2 amplification (FISH score 6) alone.
• To investigate the efficacy of AZD4547 compared with paclitaxel by assessment of
objective response rate (ORR) in all randomised patients and also in the patients
with tumours that have FGFR2 amplification (FISH score 6) alone.
• To assess the efficacy of AZD4547 and paclitaxel by assessment of the percentage
of patients without progressive disease at 8 weeks.
• To compare and assess the safety and tolerability of AZD4547 and paclitaxel.
• To investigate the PK of AZD4547 in an advanced gastric cancer patient
population.
• To investigate the possible pharmacokinetic/pharmacodynamic (PK/PD)
relationships between plasma AZD4547 exposure and plasma concentrations of
phosphate, bFGF, FGF23 and efficacy and other exploratory PD endpoints.
Test Drug
AZD4547
Active Ingredient
Benzamide, N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-4-3R,5S)-3,5-dimethyl-1-piperazinyl]
Dosage Form
tablet
Dosage
20mg
Endpoints
Efficacy
• Primary Outcome Variable:
− Change in tumour size at 8 weeks
• Secondary Outcome Variables:
− Progression Free Survival (PFS)
− Objective response rate (ORR)
− Percentage of patients without progressive disease at 8 weeks
Safety
• Adverse Events
• Deaths
• Laboratory findings (clinical chemistry, haematology, urinalysis)
• Vital signs
• Physical Examination
• Ophthalmic assessments
• Electrocardiogram parameters
• MUGA/Echo parameters
• Primary Outcome Variable:
− Change in tumour size at 8 weeks
• Secondary Outcome Variables:
− Progression Free Survival (PFS)
− Objective response rate (ORR)
− Percentage of patients without progressive disease at 8 weeks
Safety
• Adverse Events
• Deaths
• Laboratory findings (clinical chemistry, haematology, urinalysis)
• Vital signs
• Physical Examination
• Ophthalmic assessments
• Electrocardiogram parameters
• MUGA/Echo parameters
Inclution Criteria
Pre-screening part of the study
For inclusion in the pre-screening for FGFR2 status of their tumour, patients should fulfil the
following criteria:
1. Provision of signed and dated, written informed consent prior to any study specific
procedures.
2. Female or male aged 25 years or older.
3. Histological diagnosis of locally advanced or metastatic gastric adenocarcinoma
(including adenocarcinoma of the lower third of the oesophagus or the gastrooesophageal junction).
Randomised part of study
For inclusion in the randomised part of study patients should fulfil the following criteria:
1. Provision of signed and dated, written informed consent prior to any study specific
procedures, sampling and analyses. If a patient declines to participate in any
voluntary exploratory research component of the study, there will be no penalty or
loss of benefit to the patient and he/she will not be excluded from other aspects of
the study (pre-screening consent and main study consent are required).
2. Female or male aged 25 years or older.
3. Suitable for and expected to benefit from paclitaxel monotherapy.
4. Patients must have radiologically confirmed progression following 1 prior
chemotherapy or chemoradiotherapy for gastric cancer. Patients who have
progressed within 6 months following adjuvant chemotherapy may be included
upon investigators discretion.
5. World Health Organisation 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).
6. Histological diagnosis of locally advanced or metastatic gastric adenocarcinoma
(including adenocarcinoma of the lower third of the oesophagus or the gastrooesophageal junction).
7. Mandatory provision of archival or fresh tumour biopsy for confirmation of
advanced gastric cancer that has FGFR2 polysomy or gene amplification (FISH
score ≥4). Must be confirmed by AstraZeneca approved laboratory.
− Patients who had a FISH score of 1-3 when tested at pre-screening for the FGFR2
status of their tumour, can be re-tested on a fresh tumour sample, after they have
relapsed or not responded to 1st line treatment. Where 2 tests are carried out, the
results of the 2nd test must be used for assessment of eligibility.
8. At least one lesion, not previously irradiated, that can be accurately measured at
baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have
short axis ≥ 15 mm) with CT or MRI and which is suitable for accurate repeated
measurements.
− Local disease confined to the stomach or oesophagus is not considered measurable
(patients with locally advanced gastric cancer including adenocarcinoma of the
lower third of the oesophagus or the gastro-oesophageal junction must have at
least one measurable nodal lesion ≥15mm in the short axis).
9. Females should be using adequate contraceptive measures (see restrictions), 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 LH and FSH levels in the postmenopausal range.
− Documentation of irreversible surgical sterilisation by hysterectomy, and/or
bilateral oophorectomy and/or bilateral salpingectomy but excludes bilateral tubal
ligation.
10. Male patients should be willing to use barrier contraception, ie condoms.
For inclusion in the pre-screening for FGFR2 status of their tumour, patients should fulfil the
following criteria:
1. Provision of signed and dated, written informed consent prior to any study specific
procedures.
2. Female or male aged 25 years or older.
3. Histological diagnosis of locally advanced or metastatic gastric adenocarcinoma
(including adenocarcinoma of the lower third of the oesophagus or the gastrooesophageal junction).
Randomised part of study
For inclusion in the randomised part of study patients should fulfil the following criteria:
1. Provision of signed and dated, written informed consent prior to any study specific
procedures, sampling and analyses. If a patient declines to participate in any
voluntary exploratory research component of the study, there will be no penalty or
loss of benefit to the patient and he/she will not be excluded from other aspects of
the study (pre-screening consent and main study consent are required).
2. Female or male aged 25 years or older.
3. Suitable for and expected to benefit from paclitaxel monotherapy.
4. Patients must have radiologically confirmed progression following 1 prior
chemotherapy or chemoradiotherapy for gastric cancer. Patients who have
progressed within 6 months following adjuvant chemotherapy may be included
upon investigators discretion.
5. World Health Organisation 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).
6. Histological diagnosis of locally advanced or metastatic gastric adenocarcinoma
(including adenocarcinoma of the lower third of the oesophagus or the gastrooesophageal junction).
7. Mandatory provision of archival or fresh tumour biopsy for confirmation of
advanced gastric cancer that has FGFR2 polysomy or gene amplification (FISH
score ≥4). Must be confirmed by AstraZeneca approved laboratory.
− Patients who had a FISH score of 1-3 when tested at pre-screening for the FGFR2
status of their tumour, can be re-tested on a fresh tumour sample, after they have
relapsed or not responded to 1st line treatment. Where 2 tests are carried out, the
results of the 2nd test must be used for assessment of eligibility.
8. At least one lesion, not previously irradiated, that can be accurately measured at
baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have
short axis ≥ 15 mm) with CT or MRI and which is suitable for accurate repeated
measurements.
− Local disease confined to the stomach or oesophagus is not considered measurable
(patients with locally advanced gastric cancer including adenocarcinoma of the
lower third of the oesophagus or the gastro-oesophageal junction must have at
least one measurable nodal lesion ≥15mm in the short axis).
9. Females should be using adequate contraceptive measures (see restrictions), 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 LH and FSH levels in the postmenopausal range.
− Documentation of irreversible surgical sterilisation by hysterectomy, and/or
bilateral oophorectomy and/or bilateral salpingectomy but excludes bilateral tubal
ligation.
10. Male patients should be willing to use barrier contraception, ie condoms.
Exclusion Criteria
Pre-screening part of the study
Patients should not enter the pre-screening for the study if any of the following exclusion
criteria are fulfilled:
1. Involvement in the planning and/or conduct of the study (applies to both
AstraZeneca staff and/or staff at the study site).
2. Previous enrolment in the present study.
3. Judgment by the investigator that the patient should not participate in the study if
the patient is unlikely to comply with study procedures, restrictions and
requirements.
Randomised part of study
Patients should not enter the randomised part of study if any of the following exclusion
criteria are fulfilled:
1. Involvement in the planning and/or conduct of the study (applies to both
AstraZeneca staff and/or staff at the study site).
2. Previous enrolment in the present study (except for enrolment at the pre-screening
stage).
3. Participation in another clinical study with an investigational product within 4
weeks before commencing study treatment.
4. Treatment with any of the following:
− Treatment with any prior taxane therapy for gastric cancer in the past with the
exception of any taxane therapy for adjuvant or neo-adjuvant therapy given >6
months prior to study randomisation.
− Any chemotherapy, immunotherapy or anticancer agents within 4 weeks before
the first dose of study treatment
− Prior exposure to AZD4547 or to any agent with FGFR inhibition as its primary
pharmacology.
− Potent inhibitors or inducers of CYP3A4, 2C8 or 2D6 or substrates of CYP3A4
prior to the first dose of study treatment
− Major surgery (excluding placement of vascular access) within 4 weeks before the
first dose of study treatment.
− Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a
limited field of radiation for palliation within 2 weeks before the first dose of
study treatment.
− Other concomitant anti-cancer therapy except steroids
5. With the exception of alopecia, any unresolved toxicities from prior therapy with a
Common Terminology Criteria for Adverse Events (CTCAE) grade >1 at the time
of starting study treatment. Any unresolved toxicity >CTC grade 1 from previous
radiotherapy except GI or haematological toxicity which must be completely
resolved prior to commencing chemotherapy.
6. Spinal cord compression or brain metastases.
7. As judged by the investigator, any evidence of severe or uncontrolled systemic
diseases, including uncontrolled hypertension, active bleeding diatheses, or active
infection including hepatitis B, hepatitis C and human immunodeficiency virus
(HIV). Screening for chronic conditions is not required.
8. Any of the following cardiac criteria:
− Mean resting corrected QT interval (QTc) > 470 msec obtained from 3
consecutive electrocardiograms (ECGs).
− Any clinically important abnormalities in rhythm, conduction or morphology of
resting ECG e.g. complete left bundle branch block, third degree heart block.
− Any factors that increase the risk of QTc prolongation or risk of arrhythmic events
such as heart failure, hypokalaemia, congenital long QT syndrome, family history
of long QT syndrome or unexplained sudden death under 40 years of age or any
concomitant medication known to prolong the QT interval.
9. Inadequate bone marrow reserve or organ function as demonstrated by any of the
following laboratory values:
− Absolute neutrophil count < 1.5 x 109/L.
− Platelet count < 100 x 109/L.
− Haemoglobin < 90 g/L.
− Alanine aminotransferase > 2.5 times the upper limit of normal (ULN) if no
demonstrable liver metastases or > 5 times ULN in the presence of liver
metastases.
− Aspartate aminotransferase > 2.5 times ULN if no demonstrable liver metastases
or > 5 times ULN in the presence of liver metastases.
− Total bilirubin > 1.5 times ULN.
− Creatinine >1.5 times ULN concurrent with creatinine clearance < 50 ml/min
(measured or calculated by Cockcroft and Gault equation); confirmation of
creatinine clearance is only required when creatinine is > 1.5 times ULN.
− Corrected total calcium > ULN (corrected for albumin using a standard formula
that will be specified in the protocol).
− Total phosphate > ULN.
10. Any of the following ophthalmological criteria:
− Current evidence or previous history of retinal pigmented epithelium detachment
(RPED)
− Previous laser treatment or intra-ocular injection for treatment of macular
degeneration
− Current evidence or previous history of dry or wet age-related macular
degeneration
− Current evidence or previous history of retinal vein occlusion (RVO)
− Current evidence or previous history of retinal degenerative diseases
(e.g.hereditary)
− Current evidence or previous history of any other clinically relevant chorioretinal
defect
11. Refractory nausea vomiting and chronic malabsorptive states that would preclude
adequate intake and absorption of AZD4547.
12. Pregnant or breast-feeding women or women of childbearing potential with a
positive pregnancy test prior to receiving study medication.
13. History of hypersensitivity to active or inactive excipients of AZD4547 or
paclitaxel or other drugs formulated in Cremaphor EL or other drugs with a similar chemical structure or class to
AZD4547 or paclitaxel.
14. Judgment by the investigator that the patient should not participate in the study if
the patient is unlikely to comply with study procedures, restrictions and
requirements.
15. Patients with a history of another primary malignancy within 5 years prior to
starting study treatment, except adequately treated basal or squamous cell
carcinoma of the skin, carcinoma of the cervix in situ and the disease under study
Patients should not enter the pre-screening for the study if any of the following exclusion
criteria are fulfilled:
1. Involvement in the planning and/or conduct of the study (applies to both
AstraZeneca staff and/or staff at the study site).
2. Previous enrolment in the present study.
3. Judgment by the investigator that the patient should not participate in the study if
the patient is unlikely to comply with study procedures, restrictions and
requirements.
Randomised part of study
Patients should not enter the randomised part of study if any of the following exclusion
criteria are fulfilled:
1. Involvement in the planning and/or conduct of the study (applies to both
AstraZeneca staff and/or staff at the study site).
2. Previous enrolment in the present study (except for enrolment at the pre-screening
stage).
3. Participation in another clinical study with an investigational product within 4
weeks before commencing study treatment.
4. Treatment with any of the following:
− Treatment with any prior taxane therapy for gastric cancer in the past with the
exception of any taxane therapy for adjuvant or neo-adjuvant therapy given >6
months prior to study randomisation.
− Any chemotherapy, immunotherapy or anticancer agents within 4 weeks before
the first dose of study treatment
− Prior exposure to AZD4547 or to any agent with FGFR inhibition as its primary
pharmacology.
− Potent inhibitors or inducers of CYP3A4, 2C8 or 2D6 or substrates of CYP3A4
prior to the first dose of study treatment
− Major surgery (excluding placement of vascular access) within 4 weeks before the
first dose of study treatment.
− Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a
limited field of radiation for palliation within 2 weeks before the first dose of
study treatment.
− Other concomitant anti-cancer therapy except steroids
5. With the exception of alopecia, any unresolved toxicities from prior therapy with a
Common Terminology Criteria for Adverse Events (CTCAE) grade >1 at the time
of starting study treatment. Any unresolved toxicity >CTC grade 1 from previous
radiotherapy except GI or haematological toxicity which must be completely
resolved prior to commencing chemotherapy.
6. Spinal cord compression or brain metastases.
7. As judged by the investigator, any evidence of severe or uncontrolled systemic
diseases, including uncontrolled hypertension, active bleeding diatheses, or active
infection including hepatitis B, hepatitis C and human immunodeficiency virus
(HIV). Screening for chronic conditions is not required.
8. Any of the following cardiac criteria:
− Mean resting corrected QT interval (QTc) > 470 msec obtained from 3
consecutive electrocardiograms (ECGs).
− Any clinically important abnormalities in rhythm, conduction or morphology of
resting ECG e.g. complete left bundle branch block, third degree heart block.
− Any factors that increase the risk of QTc prolongation or risk of arrhythmic events
such as heart failure, hypokalaemia, congenital long QT syndrome, family history
of long QT syndrome or unexplained sudden death under 40 years of age or any
concomitant medication known to prolong the QT interval.
9. Inadequate bone marrow reserve or organ function as demonstrated by any of the
following laboratory values:
− Absolute neutrophil count < 1.5 x 109/L.
− Platelet count < 100 x 109/L.
− Haemoglobin < 90 g/L.
− Alanine aminotransferase > 2.5 times the upper limit of normal (ULN) if no
demonstrable liver metastases or > 5 times ULN in the presence of liver
metastases.
− Aspartate aminotransferase > 2.5 times ULN if no demonstrable liver metastases
or > 5 times ULN in the presence of liver metastases.
− Total bilirubin > 1.5 times ULN.
− Creatinine >1.5 times ULN concurrent with creatinine clearance < 50 ml/min
(measured or calculated by Cockcroft and Gault equation); confirmation of
creatinine clearance is only required when creatinine is > 1.5 times ULN.
− Corrected total calcium > ULN (corrected for albumin using a standard formula
that will be specified in the protocol).
− Total phosphate > ULN.
10. Any of the following ophthalmological criteria:
− Current evidence or previous history of retinal pigmented epithelium detachment
(RPED)
− Previous laser treatment or intra-ocular injection for treatment of macular
degeneration
− Current evidence or previous history of dry or wet age-related macular
degeneration
− Current evidence or previous history of retinal vein occlusion (RVO)
− Current evidence or previous history of retinal degenerative diseases
(e.g.hereditary)
− Current evidence or previous history of any other clinically relevant chorioretinal
defect
11. Refractory nausea vomiting and chronic malabsorptive states that would preclude
adequate intake and absorption of AZD4547.
12. Pregnant or breast-feeding women or women of childbearing potential with a
positive pregnancy test prior to receiving study medication.
13. History of hypersensitivity to active or inactive excipients of AZD4547 or
paclitaxel or other drugs formulated in Cremaphor EL or other drugs with a similar chemical structure or class to
AZD4547 or paclitaxel.
14. Judgment by the investigator that the patient should not participate in the study if
the patient is unlikely to comply with study procedures, restrictions and
requirements.
15. Patients with a history of another primary malignancy within 5 years prior to
starting study treatment, except adequately treated basal or squamous cell
carcinoma of the skin, carcinoma of the cervix in situ and the disease under study
The Estimated Number of Participants
-
Taiwan
90 participants
-
Global
2200 participants
