Clinical Trials List
Protocol NumberASLAN001-012
2017-04-05 - 2018-09-27
Phase II/III
Terminated2
Study ended1
ICD-10C16.0
Malignant neoplasm of cardia
ICD-9151.9
Malignant neoplasm of stomach, unspecified
A TWO-PART PHASE 2/ 3 MULTICENTRE, DOUBLE-BLIND, RANDOMIZED, PLACEBO CONTROLLED STUDY OF VARLITINIB PLUS MFOLFOX6 VERSUS PLACEBO PLUS MFOLFOX6 IN SUBJECTS WITH HER1/ HER2 CO-EXPRESSING ADVANCED OR METASTATIC GASTRIC CANCER WITHOUT PRIOR EXPOSURE TO SYSTEMIC THERAPY
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Trial Applicant
ASLAN PHARMACEUTICALS TAIWAN LIMITED
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Sponsor
ASLAN Pharmaceuticals
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 劉建廷 Division of Hematology & Oncology
- 饒坤銘 Division of Hematology & Oncology
- 陳彥豪 Division of Hematology & Oncology
- Shau-Hsuan Li Division of Hematology & Oncology
- Yu-Li Su Division of Hematology & Oncology
- Tai-Jan Chiu Division of Hematology & Oncology
- 吳佳哲 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Chung-Pin Li Division of Hematology & Oncology
- Ming-Huang Chen Division of Hematology & Oncology
- Yi-Ping Hung Division of Hematology & Oncology
- Rheun-Chuan Lee Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Che-Hung Lin Division of Hematology & Oncology
- Ming-Hung Tsai Division of Hematology & Oncology
- Chang-Fang Chiu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Study ended
Condition/Disease
HER1/ HER2 CO-EXPRESSING ADVANCED OR METASTATIC GASTRIC CANCER
Objectives
Phase 2 Part
Primary objective:
To compare the efficacy between Varlitinib in combination with mFOLFOX6 to placebo
in combination with mFOLFOX6, as measured by the percentage change from baseline in
tumor size (TS) at 12 weeks.
Phase 3 Part:
Primary Objective:
To compare the efficacy between Varlitinib in combination with mFOLFOX6 to placebo
in combination with mFOLFOX6 as measured by OS.
Test Drug
Varlitinib
Active Ingredient
Varlitinib
Dosage Form
Film Coated Tablets
Dosage
100 mg/ Tablet
Endpoints
Phase 2 Part
Primary Efficacy End Point
Percentage change from baseline in TS at Week 12: defined as the percentage change from
baseline in the sum of longest diameters of target lesions as assessed by ICR and defined
by the RECIST v1.1 criteria.
Phase 3 Part
Primary Efficacy End Point
Overall Survival (OS): Defined as the time from randomization until death by any cause.
Any subject not known to have died at the time of the analysis will be censored based on
the last recorded date on which the subject was known to be alive.
Primary Efficacy End Point
Percentage change from baseline in TS at Week 12: defined as the percentage change from
baseline in the sum of longest diameters of target lesions as assessed by ICR and defined
by the RECIST v1.1 criteria.
Phase 3 Part
Primary Efficacy End Point
Overall Survival (OS): Defined as the time from randomization until death by any cause.
Any subject not known to have died at the time of the analysis will be censored based on
the last recorded date on which the subject was known to be alive.
Inclution Criteria
Inclusion Criteria Phase 2
Subjects will be entered into this study only if they meet all of the following criteria:
1. Subjects of respective country’s legal age or older at the time of written informed
consent.
2. Subjects with histologically confirmed inoperable locally advanced, recurrent, or
metastatic adenocarcinoma of the stomach or gastro-esophageal junction (GEJ)
cancers may include Siewert Class I, II, or III types.
3. Mandatory provision of an unstained, archived tumor tissue sample in a quantity
sufficient to allow for lab analysis of HER1 and HER2 expression status. If archived
tumor tissue is not available, subject must agree to undergo fresh core biopsy to
obtain adequate tumor tissue.
4. Subjects with tumors with immunohistochemistry (IHC) evidence of expression of
HER1 (at level of + or ++ or +++) and HER-2 (at level of +, or ++) using standard
criteria. Subjects with HER-2 over expression at level of +++ determined by IHC and
subject confirmed HER2 2+ by IHC with HER2 gene amplification confirmed by
fluorescence in situ hybridization (FISH) but has contradiction to trastuzumab*.
*Trastuzumab contradiction can be determined by:
• Allergic to trastuzumab after 1 to 2 cycles of trastuzumab (without
Progressive disease [disease progression])
• Left ventricular ejection fraction (LVEF) decline ≥equal to 10% from baseline
and below 50% after 1 to 2 cycles of trastuzumab (without disease
progression)
5. Have radiographically measurable disease as defined by RECIST v1.1
6. Subjects with Eastern Cooperative Oncology Group (ECOG) performance status of
0 to 1
7. Estimated life expectancy of more than 4 months
8. Able to swallow and retain oral medication
9. Subject with adequate organ and hematological function:
a) Hematological function, as follows:
i. Absolute neutrophil count (ANC) ≥1.5 x 109
ii. Platelet count ≥100 x 109
iii. Hemoglobin ≥9 g/dL (packed red cell blood transfusions are not allowed
within one week prior to baseline hematology profile).
b) Renal functions, as follows:
i. Serum creatinine ≤1.5x upper limit of normal (ULN) or estimated
glomerular filtration rate (eGFR) >60 mL/min/1.73m2
c) Hepatic function, as follows:
i. Total bilirubin ≤1.5 x ULN
ii. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤2.5 x ULN (or ≤5 x ULN in subjects with liver metastasis)
iii. Albumin ≥25 g/L
10. Negative serum human chorionic gonadotropin (HCG)/ or urine pregnancy test within
7 days prior to randomization for premenopausal women of reproductive capacity and
for women 12 months after menopause
11. Willingness to use highly effective birth control method (failure rate <1%) while on
study.
Inclusion criteria Phase 3 Part:
1. Subjects of respective country’s legal age or older at the time of written informed
consent.
2. Subjects with histologically confirmed inoperable locally advanced, recurrent, or
metastatic adenocarcinoma of the stomach or GEJ cancers may include Siewert Class
I, II, or III types.
3. Mandatory provision of an unstained, archived tumor tissue sample in a quantity
sufficient to allow for lab analysis of HER1 and HER2 expression status. If archived
tumor tissue is not available, subject must agree to undergo fresh core biopsy to
obtain adequate tumor tissue.
4. Subjects with tumors with IHC evidence of expression of HER1 (at level of + or ++
or +++) and HER-2 (at level of +, or ++). Subjects with HER-2 over expression at
level of +++ determined by IHC and subject confirmed HER2 2+ by IHC with HER2
gene amplification confirmed by FISH but has contradiction to trastuzumab*.
*Trastuzumab contradiction can be determined by:
• Allergic to trastuzumab after 1 to 2 cycles of trastuzumab (without disease
progression)
• LVEF decline ≥equal to 10% from baseline and below 50% after 1 to 2 cycles
of trastuzumab (without disease progression)
5. Subjects with ECOG performance status of 0 to 1
6. Able to swallow and retain oral medication
7. Subject with adequate organ and hematological function:
a) Hematological function, as follows:
i. ANC ≥1.5 x 109
ii. Platelet count ≥ 100 x 109
iii. HgB ≥9 g/dL (packed red cell blood transfusions are not allowed within one week prior to baseline hematology profile).
b) Renal functions, as follows:
i. Serum creatinine ≤1.5x ULN or eGFR >60 mL/min/1.73m2
c) Hepatic function, as follows:
i. Total bilirubin ≤1.5 x ULN
ii. AST and ALT ≤2.5 x ULN (or ≤5 x ULN in subjects with liver metastasis)
iii. Albumin ≥25 g/L
8. Negative serum HCG/ or urine pregnancy test within 7 days prior to randomization
for premenopausal women of reproductive capacity and for women 12 months after
menopause
9. Willingness to use highly effective birth control method (failure rate <1%) while on
study.
Subjects will be entered into this study only if they meet all of the following criteria:
1. Subjects of respective country’s legal age or older at the time of written informed
consent.
2. Subjects with histologically confirmed inoperable locally advanced, recurrent, or
metastatic adenocarcinoma of the stomach or gastro-esophageal junction (GEJ)
cancers may include Siewert Class I, II, or III types.
3. Mandatory provision of an unstained, archived tumor tissue sample in a quantity
sufficient to allow for lab analysis of HER1 and HER2 expression status. If archived
tumor tissue is not available, subject must agree to undergo fresh core biopsy to
obtain adequate tumor tissue.
4. Subjects with tumors with immunohistochemistry (IHC) evidence of expression of
HER1 (at level of + or ++ or +++) and HER-2 (at level of +, or ++) using standard
criteria. Subjects with HER-2 over expression at level of +++ determined by IHC and
subject confirmed HER2 2+ by IHC with HER2 gene amplification confirmed by
fluorescence in situ hybridization (FISH) but has contradiction to trastuzumab*.
*Trastuzumab contradiction can be determined by:
• Allergic to trastuzumab after 1 to 2 cycles of trastuzumab (without
Progressive disease [disease progression])
• Left ventricular ejection fraction (LVEF) decline ≥equal to 10% from baseline
and below 50% after 1 to 2 cycles of trastuzumab (without disease
progression)
5. Have radiographically measurable disease as defined by RECIST v1.1
6. Subjects with Eastern Cooperative Oncology Group (ECOG) performance status of
0 to 1
7. Estimated life expectancy of more than 4 months
8. Able to swallow and retain oral medication
9. Subject with adequate organ and hematological function:
a) Hematological function, as follows:
i. Absolute neutrophil count (ANC) ≥1.5 x 109
ii. Platelet count ≥100 x 109
iii. Hemoglobin ≥9 g/dL (packed red cell blood transfusions are not allowed
within one week prior to baseline hematology profile).
b) Renal functions, as follows:
i. Serum creatinine ≤1.5x upper limit of normal (ULN) or estimated
glomerular filtration rate (eGFR) >60 mL/min/1.73m2
c) Hepatic function, as follows:
i. Total bilirubin ≤1.5 x ULN
ii. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤2.5 x ULN (or ≤5 x ULN in subjects with liver metastasis)
iii. Albumin ≥25 g/L
10. Negative serum human chorionic gonadotropin (HCG)/ or urine pregnancy test within
7 days prior to randomization for premenopausal women of reproductive capacity and
for women 12 months after menopause
11. Willingness to use highly effective birth control method (failure rate <1%) while on
study.
Inclusion criteria Phase 3 Part:
1. Subjects of respective country’s legal age or older at the time of written informed
consent.
2. Subjects with histologically confirmed inoperable locally advanced, recurrent, or
metastatic adenocarcinoma of the stomach or GEJ cancers may include Siewert Class
I, II, or III types.
3. Mandatory provision of an unstained, archived tumor tissue sample in a quantity
sufficient to allow for lab analysis of HER1 and HER2 expression status. If archived
tumor tissue is not available, subject must agree to undergo fresh core biopsy to
obtain adequate tumor tissue.
4. Subjects with tumors with IHC evidence of expression of HER1 (at level of + or ++
or +++) and HER-2 (at level of +, or ++). Subjects with HER-2 over expression at
level of +++ determined by IHC and subject confirmed HER2 2+ by IHC with HER2
gene amplification confirmed by FISH but has contradiction to trastuzumab*.
*Trastuzumab contradiction can be determined by:
• Allergic to trastuzumab after 1 to 2 cycles of trastuzumab (without disease
progression)
• LVEF decline ≥equal to 10% from baseline and below 50% after 1 to 2 cycles
of trastuzumab (without disease progression)
5. Subjects with ECOG performance status of 0 to 1
6. Able to swallow and retain oral medication
7. Subject with adequate organ and hematological function:
a) Hematological function, as follows:
i. ANC ≥1.5 x 109
ii. Platelet count ≥ 100 x 109
iii. HgB ≥9 g/dL (packed red cell blood transfusions are not allowed within one week prior to baseline hematology profile).
b) Renal functions, as follows:
i. Serum creatinine ≤1.5x ULN or eGFR >60 mL/min/1.73m2
c) Hepatic function, as follows:
i. Total bilirubin ≤1.5 x ULN
ii. AST and ALT ≤2.5 x ULN (or ≤5 x ULN in subjects with liver metastasis)
iii. Albumin ≥25 g/L
8. Negative serum HCG/ or urine pregnancy test within 7 days prior to randomization
for premenopausal women of reproductive capacity and for women 12 months after
menopause
9. Willingness to use highly effective birth control method (failure rate <1%) while on
study.
Exclusion Criteria
Exclusion Criteria Phase 2 and Phase 3 Part
Subjects will be entered into both phases of the study only if they meet none of the
following criteria:
1. Subject with HER-2 over expression at level of +++ determined by IHC or
subject confirmed HER2 2+ by IHC with HER2 gene amplification confirmed
positive by FISH.
2. Prior systemic anti-cancer treatment for inoperable locally advanced, recurrent, or
metastatic adenocarcinoma of the stomach or GEJ. However, previous (neo-) adjuvant chemotherapy is allowed if subject has progression of disease more than 6 months after (neo-) adjuvant treatment.
3. Subjects have undergone major surgery within 28 days prior to randomization.
4. Subject with brain lesion, known brain metastases (unless previously treated and well controlled for a period of at least 4 weeks).
5. Subject with malabsorption syndrome, diseases significantly affecting gastrointestinal function, extensive resection of the stomach or small bowel, or difficulty in swallowing and retaining oral medications.
6. Subjects with an uncontrolled inter current illness including, but not limited to, ongoing or active infection, NYHA III or IV congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, diabetes, hypertension, or psychiatric illness/social situations that would limit compliance with study requirements.
7. Subjects with any history of other malignancy unless in remission for more than 1 year. (Nonmelanoma skin carcinoma and carcinoma-in-site of uterine cervix treated with curative intent is not exclusionary).
8. Female subjects who are pregnant or breast feeding.
9. Subjects who were previously treated with Varlitinib.
10. Subjects who took other investigational drugs and/or used investigational medical
devices before initiating Varlitinib therapy.
11. Are currently on or have received radiation or local treatment within the past 28 days
12. Subject with unresolved or unstable serious toxicity (≥ Common Terminology Criteria for Adverse Events [CTCAE] 4.03 Grade 2) from prior administration of another investigational drug and/or prior cancer treatment (excluding hair loss)
13. Subjects with a known history of human immunodeficiency virus,
decompensated cirrhosis, hepatitis B infection with hepatitis B virus deoxyribose
nucleic acid exceeding 2000 IU/mL or hepatitis C (treatment naïve or after treatment without sustained virologic response).
14. Known history of drug addiction within the past 1 year.
15. Subjects who need continuous treatment with proton pump inhibitors during the
study period.
16. Any history or presence of clinically significant cardiovascular, respiratory, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic or psychiatric disease or any other condition which in the opinion of the Investigator could jeopardize the safety of the subject or the validity of the study results.
Subjects will be entered into both phases of the study only if they meet none of the
following criteria:
1. Subject with HER-2 over expression at level of +++ determined by IHC or
subject confirmed HER2 2+ by IHC with HER2 gene amplification confirmed
positive by FISH.
2. Prior systemic anti-cancer treatment for inoperable locally advanced, recurrent, or
metastatic adenocarcinoma of the stomach or GEJ. However, previous (neo-) adjuvant chemotherapy is allowed if subject has progression of disease more than 6 months after (neo-) adjuvant treatment.
3. Subjects have undergone major surgery within 28 days prior to randomization.
4. Subject with brain lesion, known brain metastases (unless previously treated and well controlled for a period of at least 4 weeks).
5. Subject with malabsorption syndrome, diseases significantly affecting gastrointestinal function, extensive resection of the stomach or small bowel, or difficulty in swallowing and retaining oral medications.
6. Subjects with an uncontrolled inter current illness including, but not limited to, ongoing or active infection, NYHA III or IV congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, diabetes, hypertension, or psychiatric illness/social situations that would limit compliance with study requirements.
7. Subjects with any history of other malignancy unless in remission for more than 1 year. (Nonmelanoma skin carcinoma and carcinoma-in-site of uterine cervix treated with curative intent is not exclusionary).
8. Female subjects who are pregnant or breast feeding.
9. Subjects who were previously treated with Varlitinib.
10. Subjects who took other investigational drugs and/or used investigational medical
devices before initiating Varlitinib therapy.
11. Are currently on or have received radiation or local treatment within the past 28 days
12. Subject with unresolved or unstable serious toxicity (≥ Common Terminology Criteria for Adverse Events [CTCAE] 4.03 Grade 2) from prior administration of another investigational drug and/or prior cancer treatment (excluding hair loss)
13. Subjects with a known history of human immunodeficiency virus,
decompensated cirrhosis, hepatitis B infection with hepatitis B virus deoxyribose
nucleic acid exceeding 2000 IU/mL or hepatitis C (treatment naïve or after treatment without sustained virologic response).
14. Known history of drug addiction within the past 1 year.
15. Subjects who need continuous treatment with proton pump inhibitors during the
study period.
16. Any history or presence of clinically significant cardiovascular, respiratory, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic or psychiatric disease or any other condition which in the opinion of the Investigator could jeopardize the safety of the subject or the validity of the study results.
The Estimated Number of Participants
-
Taiwan
6 participants
-
Global
50 participants
