Clinical Trials List
Protocol NumberKX-ORAX-005
NCT Number(ClinicalTrials.gov Identfier)NCT02970539
2017-04-27 - 2018-12-31
Phase I
Terminated6
ICD-10C16.0
Malignant neoplasm of cardia
A Phase 1b Study of Oraxol in Combination With Ramucirumab in Patients With Gastric, Gastro-esophageal, or Esophageal Cancers
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Trial Applicant
-
Sponsor
Athenex, Inc.
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Rheun-Chuan Lee Division of Radiology
- Chung-Pin Li Digestive System Department
- Yi-Ping Hung Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
20 Stop recruiting
Audit
None
Co-Principal Investigator
- Ming-Yu Lien Division of Hematology & Oncology
- Chang-Fang Chiu Division of Hematology & Oncology
- Chen-Yuan Lin Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 戴明燊 Division of Hematology & Oncology
- 陳佳宏 Division of Hematology & Oncology
- 張平穎 Division of Hematology & Oncology
- 葉人華 Division of Hematology & Oncology
- 詹德全 Division of General Surgery
- 吳宜穎 Division of Hematology & Oncology
- 張浩銘 Division of General Surgery
- 陳宇欽 Division of Hematology & Oncology
- 黃子權 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 曾思文 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Yao-Yu Hsieh Division of Hematology & Oncology
- Wei-Hong Cheng Division of Hematology & Oncology
- Tsu-Yi Chao Division of Hematology & Oncology
- YEN-HAO SU Division of Hematology & Oncology
- 蘇勇誠 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Co-Principal Investigator
- 陳介章 Digestive System Department
- 陳炯年 Division of General Surgery
- 林育麟 Division of Hematology & Oncology
- I-RUE LAI Division of General Surgery
- JYH-MING LIOU Digestive System Department
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
Gastric Cancer/Esophageal Cancer/Gastro-esophageal Cancer
Objectives
This is a nonrandomized, open-label, single group assignment, safety, tolerability and pharmacokinetic (PK) study to determine the MTD and optimal dosing regimen of Oraxol in combination with ramucirumab.
Test Drug
Oraxol + Ramucirumab
Active Ingredient
HM30181AK-US
Paclitaxel
Ramucirumab
Paclitaxel
Ramucirumab
Dosage Form
Capsule
tablet
solution
solution
tablet
solution
solution
Dosage
30
15
100
500
15
100
500
Endpoints
Primary Endpoint:
The primary endpoint of determining the MTD will be based on DLT.
Secondary Endpoints:
Safety: Evaluation of AEs and clinical laboratory data
Recommended Phase 2 Dose: Evaluation of the 3-day MTD for Oraxol in combination with
ramucirumab including safety, tolerability, and pharmacokinetics
Pharmacokinetic: Evaluation of PK parameters for paclitaxel and its major metabolites
Activity: Tumor response will be evaluated according to RECIST v1.1:
o Response rate
o Progression-free survival
o Overall survival
The primary endpoint of determining the MTD will be based on DLT.
Secondary Endpoints:
Safety: Evaluation of AEs and clinical laboratory data
Recommended Phase 2 Dose: Evaluation of the 3-day MTD for Oraxol in combination with
ramucirumab including safety, tolerability, and pharmacokinetics
Pharmacokinetic: Evaluation of PK parameters for paclitaxel and its major metabolites
Activity: Tumor response will be evaluated according to RECIST v1.1:
o Response rate
o Progression-free survival
o Overall survival
Inclution Criteria
Inclusion Criteria
Subjects must meet all of the following criteria to be included in this study:
1. Signed written informed consent
2. ≥18 years of age
3. Histologically or cytologically confirmed diagnosis of advanced stage gastric,
gastroesophageal, or esophageal adenocarcinoma with disease progression on or after prior
fluoropyrimidine- or platinum-containing chemotherapy
4. Have documented testing for HER2‐neu overexpression, and for those with tumors
overexpressing HER2‐neu, have documented progression on Trastuzumab‐containing therapy
5. Measurable disease on computed tomography (CT) scan of thorax, abdomen, and pelvis per
RECIST v1.1 criteria
6. Able to swallow oral medication as an intact dosage form
7. Adequate hematologic status as demonstrated by not requiring transfusion support or
granulocyte-colony stimulating factor (G-CSF) to maintain:
ANC ≥1500 cells/mm3
Platelet count ≥100 x 109
/L
Hemoglobin ≥10 g/dL
8. Adequate liver function as demonstrated by:
Total bilirubin of ≤1.5 mg/dL or ≤2.0 mg/dL for subjects with liver metastasis
Alanine aminotransferase (ALT) ≤3 x upper limit of normal (ULN) or ≤5 x ULN if liver
metastasis is present
Alkaline phosphatase ≤3 x ULN or ≤5 x ULN if bone or liver metastasis is present
9. Adequate renal function as demonstrated by serum creatinine ≤1.5 x ULN or creatinine
clearance calculation ≥60 mL/min as calculated by the Cockroft and Gault formula
10. Normal prothrombin time (PT) or international normalized ratio (INR) and normal activated
partial thromboplastin time (aPTT)
11. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
12. Life expectancy of at least 3 months
13. Women must be postmenopausal (>12 months without menses) or surgically sterile (ie, by
hysterectomy and/or bilateral oophorectomy) or must be using effective contraception (ie,
oral contraceptives, intrauterine device, double barrier method of condom and spermicide)
and agree to continue use of contraception for 30 days after their last dose of study drug.
14. Sexually active male subjects must use a barrier method of contraception during the study
and agree to continue the use of male contraception for at least 30 days after the last dose of
study drug.
Subjects must meet all of the following criteria to be included in this study:
1. Signed written informed consent
2. ≥18 years of age
3. Histologically or cytologically confirmed diagnosis of advanced stage gastric,
gastroesophageal, or esophageal adenocarcinoma with disease progression on or after prior
fluoropyrimidine- or platinum-containing chemotherapy
4. Have documented testing for HER2‐neu overexpression, and for those with tumors
overexpressing HER2‐neu, have documented progression on Trastuzumab‐containing therapy
5. Measurable disease on computed tomography (CT) scan of thorax, abdomen, and pelvis per
RECIST v1.1 criteria
6. Able to swallow oral medication as an intact dosage form
7. Adequate hematologic status as demonstrated by not requiring transfusion support or
granulocyte-colony stimulating factor (G-CSF) to maintain:
ANC ≥1500 cells/mm3
Platelet count ≥100 x 109
/L
Hemoglobin ≥10 g/dL
8. Adequate liver function as demonstrated by:
Total bilirubin of ≤1.5 mg/dL or ≤2.0 mg/dL for subjects with liver metastasis
Alanine aminotransferase (ALT) ≤3 x upper limit of normal (ULN) or ≤5 x ULN if liver
metastasis is present
Alkaline phosphatase ≤3 x ULN or ≤5 x ULN if bone or liver metastasis is present
9. Adequate renal function as demonstrated by serum creatinine ≤1.5 x ULN or creatinine
clearance calculation ≥60 mL/min as calculated by the Cockroft and Gault formula
10. Normal prothrombin time (PT) or international normalized ratio (INR) and normal activated
partial thromboplastin time (aPTT)
11. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
12. Life expectancy of at least 3 months
13. Women must be postmenopausal (>12 months without menses) or surgically sterile (ie, by
hysterectomy and/or bilateral oophorectomy) or must be using effective contraception (ie,
oral contraceptives, intrauterine device, double barrier method of condom and spermicide)
and agree to continue use of contraception for 30 days after their last dose of study drug.
14. Sexually active male subjects must use a barrier method of contraception during the study
and agree to continue the use of male contraception for at least 30 days after the last dose of
study drug.
Exclusion Criteria
Exclusion Criteria
Subjects who meet any of the following criteria will be excluded from this study:
1. Unresolved toxicity from previous anticancer treatments, including investigational products
(subjects must have recovered all unacceptable toxicity to ≤ Grade 1 Common Terminology
Criteria for Adverse Events [CTCAE] toxicity). This does not extend to symptoms or
findings that are attributable to the underlying disease.
2. Received investigational products within 14 days or 5 half-lives of the first study dosing day,
whichever is longer
3. Are currently receiving other medications or radiation intended for the treatment of their
malignancy
4. Central nervous system metastases, including leptomeningeal involvement
5. Women of childbearing potential who are pregnant or breastfeeding
6. Currently taking a concomitant medication, other than a premedication, that is:
A known P-glycoprotein (P-gp) inhibitor or inducer. Subjects who are taking such
medications but who are otherwise eligible may be enrolled if they discontinue the
medication ≥1 week before dosing
An oral medication with a narrow therapeutic index known to be a P-gp substrate within
24 hours prior to start of dosing in the study
Medications known to be clinically significant inhibitors (gemfibrozil) or inducers
(rifampin) of CYP2C8 or medications known to be strong cytochrome P450 (CYP) 3A4
inhibitors (eg, ketoconazole) or inducers (eg, rifampin or St. John's Wort). Subjects who
are currently taking such medications but who are otherwise eligible may be enrolled if
they discontinue the medication 1 week before dosing and remain off that medication
during treatment with Oraxol.
7. Require therapeutic use of anticoagulants other than daily aspirin or low molecular weight
heparin
8. Require therapeutic use of nonsteroidal anti-inflammatory drugs (NSAIDs)
9. Unable to receive iv contrast for required CT scans
10. Systolic blood pressure >140mm Hg or diastolic blood pressure > 90 mm Hg
11. Grade 3 gastrointestinal (GI) bleeding within 3 months prior to screening
12. Arterial thromboembolic event including, but not limited to, myocardial infarction, transient
ischemic attack, or cerebrovascular accident within 6 months of enrollment
13. Deep vein thrombosis (DVT) or pulmonary embolus which require use of oral anticoagulants
or, if on low molecular weight heparin, have not been on a stable dose for at least 2 weeks
14. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection,
symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, poorly
controlled diabetes or diabetes with established vascular complications, chronic pulmonary
disease requiring oxygen, known bleeding disorders, or any concomitant illness or social
situation that would limit compliance with study requirements
15. Major surgery to the upper GI tract, or have a history of GI disease or other medical
condition that, in the opinion of the investigator may interfere with oral drug absorption
16. History of hypersensitivity to paclitaxel, not attributed to a hypersensitivity type reaction to
Cremophor®, or history of hypersensitivity type reaction to polysorbate 80 or other
components of the formulation of Oraxol
17. History of developing any condition during prior treatment with ramucirumab for which
ramucirumab must be permanently discontinued according to the ramucirumab label.
Subjects who meet any of the following criteria will be excluded from this study:
1. Unresolved toxicity from previous anticancer treatments, including investigational products
(subjects must have recovered all unacceptable toxicity to ≤ Grade 1 Common Terminology
Criteria for Adverse Events [CTCAE] toxicity). This does not extend to symptoms or
findings that are attributable to the underlying disease.
2. Received investigational products within 14 days or 5 half-lives of the first study dosing day,
whichever is longer
3. Are currently receiving other medications or radiation intended for the treatment of their
malignancy
4. Central nervous system metastases, including leptomeningeal involvement
5. Women of childbearing potential who are pregnant or breastfeeding
6. Currently taking a concomitant medication, other than a premedication, that is:
A known P-glycoprotein (P-gp) inhibitor or inducer. Subjects who are taking such
medications but who are otherwise eligible may be enrolled if they discontinue the
medication ≥1 week before dosing
An oral medication with a narrow therapeutic index known to be a P-gp substrate within
24 hours prior to start of dosing in the study
Medications known to be clinically significant inhibitors (gemfibrozil) or inducers
(rifampin) of CYP2C8 or medications known to be strong cytochrome P450 (CYP) 3A4
inhibitors (eg, ketoconazole) or inducers (eg, rifampin or St. John's Wort). Subjects who
are currently taking such medications but who are otherwise eligible may be enrolled if
they discontinue the medication 1 week before dosing and remain off that medication
during treatment with Oraxol.
7. Require therapeutic use of anticoagulants other than daily aspirin or low molecular weight
heparin
8. Require therapeutic use of nonsteroidal anti-inflammatory drugs (NSAIDs)
9. Unable to receive iv contrast for required CT scans
10. Systolic blood pressure >140mm Hg or diastolic blood pressure > 90 mm Hg
11. Grade 3 gastrointestinal (GI) bleeding within 3 months prior to screening
12. Arterial thromboembolic event including, but not limited to, myocardial infarction, transient
ischemic attack, or cerebrovascular accident within 6 months of enrollment
13. Deep vein thrombosis (DVT) or pulmonary embolus which require use of oral anticoagulants
or, if on low molecular weight heparin, have not been on a stable dose for at least 2 weeks
14. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection,
symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, poorly
controlled diabetes or diabetes with established vascular complications, chronic pulmonary
disease requiring oxygen, known bleeding disorders, or any concomitant illness or social
situation that would limit compliance with study requirements
15. Major surgery to the upper GI tract, or have a history of GI disease or other medical
condition that, in the opinion of the investigator may interfere with oral drug absorption
16. History of hypersensitivity to paclitaxel, not attributed to a hypersensitivity type reaction to
Cremophor®, or history of hypersensitivity type reaction to polysorbate 80 or other
components of the formulation of Oraxol
17. History of developing any condition during prior treatment with ramucirumab for which
ramucirumab must be permanently discontinued according to the ramucirumab label.
The Estimated Number of Participants
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Taiwan
32 participants
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Global
32 participants
