Clinical Trials List
Protocol NumberD081BC00004
2014-06-01 - 2017-12-31
Phase III
Terminated5
ICD-10C16.9
Malignant neoplasm of stomach, unspecified
ICD-9151.9
Malignant neoplasm of stomach, unspecified
A randomized, double-blinded, placebo controlled, multicentre phase III study to assess the efficacy and safety of olaparib (AZD2281) in combination with paclitaxel, compared to placebo in combination with paclitaxel, in Asian patients with advanced gastric cancer (including the gastro-oesophageal junction) who have progressed following first line therapy
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Trial Applicant
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Sponsor
AstraZeneca plc.
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Wen-Chi Shen Division of Hematology & Oncology
- 黃文冠 Division of Hematology & Oncology
- Hung-Chih Hsu Division of Hematology & Oncology
- Yung-Chia Kao Division of Hematology & Oncology
- Tsai-Sheng Yang Division of Hematology & Oncology
- Chia-Hsun Hsieh Division of Hematology & Oncology
- Ming-Mo Hou Division of Hematology & Oncology
- Wen-Chi Chou Division of Hematology & Oncology
- 吳教恩 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 陳彥豪 Division of Hematology & Oncology
- 劉建廷 Division of Hematology & Oncology
- Tai-Jan Chiu Division of Hematology & Oncology
- Yu-Li Su Division of Hematology & Oncology
- Shau-Hsuan Li Division of Hematology & Oncology
- 陳彥仰 Division of Hematology & Oncology
- 吳佳哲 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Ching-Chan Lin Division of Hematology & Oncology
- Ming-Yu Lien Division of Hematology & Oncology
- Chang-Fang Chiu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Yan-Shen Shan Division of Hematology & Oncology
- Shang-Yin Wu Division of Hematology & Oncology
- Wei-Pang Chung Division of Hematology & Oncology
- Yu-Min Yeh Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Rheun-Chuan Lee Division of Radiology
- Chung-Pin Li Digestive System Department
- Ming-Huang Chen Division of Hematology & Oncology
- Yi-Ping Hung Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
advanced gastric cancer
Objectives
To investigate the efficacy of olaparib when given in combination with paclitaxel
compared to placebo in combination with paclitaxel as defined by overall survival
(OS) in all patients, and a subset of patients (to be specified prior to the interim
analysis), with advanced gastric cancer (including the gastro-oesophageal junction
[GEJ]) who have progressed following first-line therapy
Test Drug
Olaparib
Active Ingredient
AZD2281
Dosage Form
film-coated
Dosage
100, 150
Endpoints
To investigate the efficacy of olaparib when given in combination with paclitaxel
compared to placebo in combination with paclitaxel as defined by overall survival
(OS) in all patients, and a subset of patients (to be specified prior to the interim
analysis), with advanced gastric cancer (including the gastro-oesophageal junction
[GEJ]) who have progressed following first-line therapy
compared to placebo in combination with paclitaxel as defined by overall survival
(OS) in all patients, and a subset of patients (to be specified prior to the interim
analysis), with advanced gastric cancer (including the gastro-oesophageal junction
[GEJ]) who have progressed following first-line therapy
Inclution Criteria
For inclusion in the study patients should fulfil the following criteria:
1. Provision of fully informed consent prior to any study specific procedures.
2. Patients must be ≥18 years of age. Age ≥20 if Japanese.
3. Advanced gastric cancer (including GEJ) that has progressed following first-line
therapy.
− The 1st line regimen must have contained doublet 5-fluoropyrimidine and
platinum based regimen.
− Relapse within 6 months of completion of adjuvant/neoadjuvant chemotherapy
containing doublet 5-fluoropyrimidine and platinum based regimen could be
considered as 1st line therapy.
4. Previous adjuvant/neoadjuvant chemotherapy is allowed, if completed more than 6 months prior to starting the 1st line therapy.
5. Provision of tumour sample (from either a resection or biopsy). For biopsy based
samples, 3 to 5 (minimum of 3) biopsy samples must be provided.
6. Patients are willing and able to comply with the protocol for the duration of the
study including undergoing treatment and scheduled visits and examinations.
7. ECOG performance status ≤ 1.
8. Patients must have a life expectancy ≥ 16 weeks from proposed first dose date.
9. Patients must have acceptable bone marrow, liver and renal function measured
within 28 days prior to administration of study treatment as defined below:
− Absolute neutrophil count (ANC) ≥ 1.5 x 109
− White blood cells (WBC) > 3 x 109
− Platelet count ≥ 100 x 109
− Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
− AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case it must be ≤ 5x ULN
− Serum creatinine ≤ 1.5 x institutional ULN
10. At least one lesion (measurable and/or non-measurable) that can be accurately
assessed by imaging (CT/MRI) at baseline and following up visits.
− Local disease confined to the stomach or GEJ mass is classified as “nonmeasurable”
11. Evidence of non-childbearing status for women of childbearing potential, or
postmenopausal status: negative urine or serum pregnancy test within 28 days of
study treatment, confirmed prior to treatment on day 1. Postmenopausal is defined
as:
− Amenorrheic for 1 year or more following cessation of exogenous hormonal
treatments
− LH and FSH levels in the post menopausal range for women under 50
− Radiation-induced oophorectomy with last menses >1 year ago
− Chemotherapy-induced menopause with >1 year interval since last menses
− Or surgical sterilisation (bilateral oophorectomy or hysterectomy)
12. See Appendix G for additional inclusion criteria for the Optional pharmacogenetics research.
1. Provision of fully informed consent prior to any study specific procedures.
2. Patients must be ≥18 years of age. Age ≥20 if Japanese.
3. Advanced gastric cancer (including GEJ) that has progressed following first-line
therapy.
− The 1st line regimen must have contained doublet 5-fluoropyrimidine and
platinum based regimen.
− Relapse within 6 months of completion of adjuvant/neoadjuvant chemotherapy
containing doublet 5-fluoropyrimidine and platinum based regimen could be
considered as 1st line therapy.
4. Previous adjuvant/neoadjuvant chemotherapy is allowed, if completed more than 6 months prior to starting the 1st line therapy.
5. Provision of tumour sample (from either a resection or biopsy). For biopsy based
samples, 3 to 5 (minimum of 3) biopsy samples must be provided.
6. Patients are willing and able to comply with the protocol for the duration of the
study including undergoing treatment and scheduled visits and examinations.
7. ECOG performance status ≤ 1.
8. Patients must have a life expectancy ≥ 16 weeks from proposed first dose date.
9. Patients must have acceptable bone marrow, liver and renal function measured
within 28 days prior to administration of study treatment as defined below:
− Absolute neutrophil count (ANC) ≥ 1.5 x 109
− White blood cells (WBC) > 3 x 109
− Platelet count ≥ 100 x 109
− Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
− AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case it must be ≤ 5x ULN
− Serum creatinine ≤ 1.5 x institutional ULN
10. At least one lesion (measurable and/or non-measurable) that can be accurately
assessed by imaging (CT/MRI) at baseline and following up visits.
− Local disease confined to the stomach or GEJ mass is classified as “nonmeasurable”
11. Evidence of non-childbearing status for women of childbearing potential, or
postmenopausal status: negative urine or serum pregnancy test within 28 days of
study treatment, confirmed prior to treatment on day 1. Postmenopausal is defined
as:
− Amenorrheic for 1 year or more following cessation of exogenous hormonal
treatments
− LH and FSH levels in the post menopausal range for women under 50
− Radiation-induced oophorectomy with last menses >1 year ago
− Chemotherapy-induced menopause with >1 year interval since last menses
− Or surgical sterilisation (bilateral oophorectomy or hysterectomy)
12. See Appendix G for additional inclusion criteria for the Optional pharmacogenetics research.
Exclusion Criteria
Patients should not enter 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 randomization in the present study.
3. More than one prior chemotherapy regimen (except for adjuvant/neoadjuvant
chemotherapy with more than 6 month wash out period) for the treatment of gastric cancer in the advanced setting.
4. Any previous treatment with a PARP inhibitor, including olaparib.
5. Any previous treatment with a taxane, including paclitaxel and docetaxel.
6. Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours
curatively treated with no evidence of disease for ≥5 years.
7. HER2 positive patients.
8. Patients unable to swallow orally administered medication.
9. Treatment with any investigational product during the last 14 days before the
randomization (or a longer period depending on the defined characteristics of the
agents used).
10. Patients receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), within 3 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used). The patient can receive a stable dose of bisphosphonates or denusomab for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment.
11. Concomitant use of known potent CYP3A4 inhibitors such as ketoconazole,
itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and
nelfinavir.
12. With the exception of alopecia, any ongoing toxicities (>CTCAE grade 1) caused
by previous cancer therapy.
13. Intestinal obstruction or CTCAE grade 3 or grade 4 upper GI bleeding within 4
weeks before the randomization.
14. Resting ECG with measurable QTc > 470 msec on 2 or more time points within a
24 hour period or family history of long QT syndrome.
15. Patients with myelodysplastic syndrome/acute myeloid leukaemia.
16. Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
17. Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
18. Patients considered a poor medical risk due to a serious, uncontrolled medical
disorder, non-malignant systemic disease or active, uncontrolled infection.
Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive bilateral interstitial lung disease on HRCT scan or any psychiatric disorder that prohibits obtaining informed consent.
19. Immunocompromised patients, e.g., patients who are known to be serologically
positive for human immunodeficiency virus (HIV).
20. Patients with known active hepatic disease (i.e. Hepatitis B or C)
21. Patients with a known hypersensitivity to olaparib, paclitaxel or any of the
excipients of the product.
22. Pregnant and breastfeeding women.
23. See Appendix G for additional exclusion criteria for the Optional harmacogenetics research.
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 randomization in the present study.
3. More than one prior chemotherapy regimen (except for adjuvant/neoadjuvant
chemotherapy with more than 6 month wash out period) for the treatment of gastric cancer in the advanced setting.
4. Any previous treatment with a PARP inhibitor, including olaparib.
5. Any previous treatment with a taxane, including paclitaxel and docetaxel.
6. Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours
curatively treated with no evidence of disease for ≥5 years.
7. HER2 positive patients.
8. Patients unable to swallow orally administered medication.
9. Treatment with any investigational product during the last 14 days before the
randomization (or a longer period depending on the defined characteristics of the
agents used).
10. Patients receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), within 3 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used). The patient can receive a stable dose of bisphosphonates or denusomab for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment.
11. Concomitant use of known potent CYP3A4 inhibitors such as ketoconazole,
itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and
nelfinavir.
12. With the exception of alopecia, any ongoing toxicities (>CTCAE grade 1) caused
by previous cancer therapy.
13. Intestinal obstruction or CTCAE grade 3 or grade 4 upper GI bleeding within 4
weeks before the randomization.
14. Resting ECG with measurable QTc > 470 msec on 2 or more time points within a
24 hour period or family history of long QT syndrome.
15. Patients with myelodysplastic syndrome/acute myeloid leukaemia.
16. Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
17. Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
18. Patients considered a poor medical risk due to a serious, uncontrolled medical
disorder, non-malignant systemic disease or active, uncontrolled infection.
Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive bilateral interstitial lung disease on HRCT scan or any psychiatric disorder that prohibits obtaining informed consent.
19. Immunocompromised patients, e.g., patients who are known to be serologically
positive for human immunodeficiency virus (HIV).
20. Patients with known active hepatic disease (i.e. Hepatitis B or C)
21. Patients with a known hypersensitivity to olaparib, paclitaxel or any of the
excipients of the product.
22. Pregnant and breastfeeding women.
23. See Appendix G for additional exclusion criteria for the Optional harmacogenetics research.
The Estimated Number of Participants
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Taiwan
35 participants
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Global
644 participants
