Clinical Trials List
Protocol NumberKX-ORAX-010
NCT Number(ClinicalTrials.gov Identfier)NCT03544567
2019-06-01 - 2022-12-31
Phase II
Recruiting2
ICD-10D18.01
Hemangioma of skin and subcutaneous tissue
ICD-9228.01
Hemangioma of skin and subcutaneous tissue
A Pilot Study of Oraxol in Subjects With Cutaneous Angiosarcoma
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Trial Applicant
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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
- 吳宏達 Division of Radiology
- Ta-Chung Chao Division of Hematology & Oncology
- CHERNG-KANG PERNG Division of Plastic Surgery
- San-Chi Chen Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Chia-Chi Lin Division of Hematology & Oncology
- 張端瑩 Division of Hematology & Oncology
- Jih-Hsiang Lee Division of Hematology & Oncology
- RUEY-LONG HONG Division of Hematology & Oncology
- Hsiang-Fong Kao Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Cutaneous Angiosarcoma
Objectives
This is a non-blinded, multi-center, open-label, pilot study to evaluate the activity, safety, and tolerability of Oraxol in subjects with cutaneous angiosarcoma.
Oraxol will be administered once daily for 3 consecutive days every week during the Treatment Period from Weeks 1 through 25.
Subjects who do not have documented disease progression by the end of the Treatment Period will be eligible to receive therapy in the Treatment Extension Period; Oraxol may be administered from Week 26 onwards.
Test Drug
Oraxol
Active Ingredient
HM30181AK-US
Paclitaxel
Paclitaxel
Dosage Form
Capsules
tablets
tablets
Dosage
30
15
15
Endpoints
Primary Outcome Measures :
Response rate [ Time Frame: 6 months ]
To determine the response rate 6 months after initiation of treatment with Oraxol in subjects with cutaneous angiosarcoma
Secondary Outcome Measures :
Incidence of Treatment-Emergent Adverse Events [ Time Frame: an average of 1 year ]
Overall safety and tolerability of Oraxol in subjects with cutaneous angiosarcoma
Progression free survival [ Time Frame: 24 months ]
To determine the progression-free survival (PFS) after initiation of treatment with Oraxol in subjects with cutaneous angiosarcoma
Overall Survival (OS) [ Time Frame: 24 months ]
To determine the overall survival (OS) after initiation of treatment with Oraxol in subjects with cutaneous angiosarcoma
Duration of response [ Time Frame: 24 months ]
To determine the duration of response in subjects with cutaneous angiosarcoma
Time to best response [ Time Frame: 24 months ]
To determine the time to best response in subjects with cutaneous angiosarcoma
Response rate [ Time Frame: 6 months ]
To determine the response rate 6 months after initiation of treatment with Oraxol in subjects with cutaneous angiosarcoma
Secondary Outcome Measures :
Incidence of Treatment-Emergent Adverse Events [ Time Frame: an average of 1 year ]
Overall safety and tolerability of Oraxol in subjects with cutaneous angiosarcoma
Progression free survival [ Time Frame: 24 months ]
To determine the progression-free survival (PFS) after initiation of treatment with Oraxol in subjects with cutaneous angiosarcoma
Overall Survival (OS) [ Time Frame: 24 months ]
To determine the overall survival (OS) after initiation of treatment with Oraxol in subjects with cutaneous angiosarcoma
Duration of response [ Time Frame: 24 months ]
To determine the duration of response in subjects with cutaneous angiosarcoma
Time to best response [ Time Frame: 24 months ]
To determine the time to best response in subjects with cutaneous angiosarcoma
Inclution Criteria
Inclusion Criteria:
Willingness and ability to give informed consent, prior to any study-specific procedures and willingness to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
Age of 18 years or older
Histologically-confirmed cutaneous angiosarcoma that is not amenable to curative intent surgery (eg, locally advanced disease and disease for which surgical resection would carry an unacceptable risk of recurrence or morbidity to the subject)
Subjects who have not received taxanes for the treatment of angiosarcoma
Measurable disease per RECIST v.1.1
Eastern Cooperative Oncology Group (ECOG) performance status ≤1
Resolution of all acute AEs resulting from prior cancer therapies to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE v4.03) Grade ≤1 or to that subject's baseline
Adequate organ function as defined by the following criteria:
Adequate renal function as evidenced by serum creatinine ≤1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥50 mL/min per the Cockcroft and Gault formula
Adequate bone marrow function as evidenced by:
absolute neutrophil count (ANC) ≥1.5 × 109/L
hemoglobin ≥9.0 g/dL (<9.0 g/dL is acceptable if it is corrected by transfusion), and
platelet count ≥100 × 109/L
Adequate liver function as evidenced by
total bilirubin within normal limits,
alanine aminotransferase (ALT) ≤3×ULN, and aspartate aminotransferase (AST) ≤3×ULN,
gamma-glutamyl transferase (GGT) ≤10×ULN, and
alkaline phosphatase ≤3×ULN
Able to swallow pills whole and retain oral medications
Sexually active male subjects including men who are sterile (including vasectomy confirmed by post vasectomy semen analysis) must agree to use a condom with spermicide and to not donate sperm from the time of Screening until 6 months following the last dose of Oraxol
Women of non-child bearing potential due to surgical sterilization (at least 6 weeks following surgical bilateral oophorectomy with or without hysterectomy or tubal ligation) confirmed by medical history or menopause (ie, no menstrual bleeding for more than 12 months in a woman aged ≥45 years), OR women of childbearing potential who test negative for pregnancy at time of enrollment based on serum pregnancy test must be using a highly effective method of contraception from the time of Screening until 6 months following the last dose of Oraxol. Note: Highly effective methods of contraception that result in a low failure rate (ie, <1% per year) when used consistently and correctly include combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner, or sexual abstinence. True abstinence, when in line with the preferred and usual lifestyle of the subject, is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of study participation and for 6 months post-Oraxol administration. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the subject. Periodic abstinence (eg, calendar, ovulation, symptothermal, and post-ovulation method) and withdrawal are not acceptable methods of contraception.
Life expectancy of at least 3 months, in the opinion of the Investigator
Willingness and ability to give informed consent, prior to any study-specific procedures and willingness to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
Age of 18 years or older
Histologically-confirmed cutaneous angiosarcoma that is not amenable to curative intent surgery (eg, locally advanced disease and disease for which surgical resection would carry an unacceptable risk of recurrence or morbidity to the subject)
Subjects who have not received taxanes for the treatment of angiosarcoma
Measurable disease per RECIST v.1.1
Eastern Cooperative Oncology Group (ECOG) performance status ≤1
Resolution of all acute AEs resulting from prior cancer therapies to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE v4.03) Grade ≤1 or to that subject's baseline
Adequate organ function as defined by the following criteria:
Adequate renal function as evidenced by serum creatinine ≤1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥50 mL/min per the Cockcroft and Gault formula
Adequate bone marrow function as evidenced by:
absolute neutrophil count (ANC) ≥1.5 × 109/L
hemoglobin ≥9.0 g/dL (<9.0 g/dL is acceptable if it is corrected by transfusion), and
platelet count ≥100 × 109/L
Adequate liver function as evidenced by
total bilirubin within normal limits,
alanine aminotransferase (ALT) ≤3×ULN, and aspartate aminotransferase (AST) ≤3×ULN,
gamma-glutamyl transferase (GGT) ≤10×ULN, and
alkaline phosphatase ≤3×ULN
Able to swallow pills whole and retain oral medications
Sexually active male subjects including men who are sterile (including vasectomy confirmed by post vasectomy semen analysis) must agree to use a condom with spermicide and to not donate sperm from the time of Screening until 6 months following the last dose of Oraxol
Women of non-child bearing potential due to surgical sterilization (at least 6 weeks following surgical bilateral oophorectomy with or without hysterectomy or tubal ligation) confirmed by medical history or menopause (ie, no menstrual bleeding for more than 12 months in a woman aged ≥45 years), OR women of childbearing potential who test negative for pregnancy at time of enrollment based on serum pregnancy test must be using a highly effective method of contraception from the time of Screening until 6 months following the last dose of Oraxol. Note: Highly effective methods of contraception that result in a low failure rate (ie, <1% per year) when used consistently and correctly include combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner, or sexual abstinence. True abstinence, when in line with the preferred and usual lifestyle of the subject, is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of study participation and for 6 months post-Oraxol administration. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the subject. Periodic abstinence (eg, calendar, ovulation, symptothermal, and post-ovulation method) and withdrawal are not acceptable methods of contraception.
Life expectancy of at least 3 months, in the opinion of the Investigator
Exclusion Criteria
Exclusion Criteria:
Subjects with metastases outside of local lymph node involvement
Concurrent treatment or participation on other therapeutic clinical trial for angiosarcoma. Participation in companion studies sponsored by local institutions, including biological correlates, is permitted.
Women who are pregnant or breastfeeding
Receipt of systemic cytotoxic therapy, including investigational agents, within 14 days or 5 half-lives of the first study dosing day, whichever is longer
Major surgery or trauma within 28 days prior to first dose of investigational product. Note: The following are not considered to be major procedures and are permitted before treatment administration: thoracentesis, paracentesis, catheter placement, port placement, laparoscopy, thoracoscopy, tube thoracostomy, bronchoscopy, endoscopic ultrasonographic procedures, mediastinoscopy, skin biopsies, and imaging-guided biopsy for diagnostic purposes
Subjects who have received wide-field radiotherapy to the pelvis ≤3 months (defined as >50% of volume of pelvic bones or equivalent) or limited-field radiation for palliation ≤3 months prior to treatment administration. Angiosarcoma lesions in the radiation field are not evaluable unless they have developed progressive disease following radiation.
History of brain involvement with cancer, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease.
Angina, myocardial infarction, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG) within 3 months prior to treatment administration
Active bleeding or bleeding diathesis actively requiring transfusions; Note: subjects with cutaneous ulcers from angiosarcoma or who have skin lesions with bleeding are allowed to participate.
Thrombolytic use (except to maintain IV catheters) within 10 days prior to treatment administration
Presence of a malabsorption syndrome or major resection of the stomach or small bowel that could affect the absorption of Oraxol
Known active viral or nonviral hepatitis or cirrhosis
Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
Active infection that requires systemic treatment
Concurrent use of a strong cytochrome P450 (CYP) 3A4 inducer (eg, rifampin or St. John's Wort) or a strong CYP3A4 inhibitor (eg, ketoconazole) within 14 days prior to treatment administration
Concurrent use of a strong CYP2C8 inhibitor (eg, gemfibrozil) or inducer (eg, rifampin) within 14 days prior to treatment administration
Concurrent use of an oral medication with a narrow therapeutic index known to be a P-glycoprotein (P-gp) substrate within 24 hours prior to treatment administration
Concurrent use of a medication known to be a strong P-gp inhibitor or inducer within 14 days prior to treatment administration
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
Other severe acute or chronic medical (including bone marrow suppressive diseases) or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation, impede the ability of the subject to complete all protocol-specified activities, or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for this study
Subjects with metastases outside of local lymph node involvement
Concurrent treatment or participation on other therapeutic clinical trial for angiosarcoma. Participation in companion studies sponsored by local institutions, including biological correlates, is permitted.
Women who are pregnant or breastfeeding
Receipt of systemic cytotoxic therapy, including investigational agents, within 14 days or 5 half-lives of the first study dosing day, whichever is longer
Major surgery or trauma within 28 days prior to first dose of investigational product. Note: The following are not considered to be major procedures and are permitted before treatment administration: thoracentesis, paracentesis, catheter placement, port placement, laparoscopy, thoracoscopy, tube thoracostomy, bronchoscopy, endoscopic ultrasonographic procedures, mediastinoscopy, skin biopsies, and imaging-guided biopsy for diagnostic purposes
Subjects who have received wide-field radiotherapy to the pelvis ≤3 months (defined as >50% of volume of pelvic bones or equivalent) or limited-field radiation for palliation ≤3 months prior to treatment administration. Angiosarcoma lesions in the radiation field are not evaluable unless they have developed progressive disease following radiation.
History of brain involvement with cancer, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease.
Angina, myocardial infarction, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG) within 3 months prior to treatment administration
Active bleeding or bleeding diathesis actively requiring transfusions; Note: subjects with cutaneous ulcers from angiosarcoma or who have skin lesions with bleeding are allowed to participate.
Thrombolytic use (except to maintain IV catheters) within 10 days prior to treatment administration
Presence of a malabsorption syndrome or major resection of the stomach or small bowel that could affect the absorption of Oraxol
Known active viral or nonviral hepatitis or cirrhosis
Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
Active infection that requires systemic treatment
Concurrent use of a strong cytochrome P450 (CYP) 3A4 inducer (eg, rifampin or St. John's Wort) or a strong CYP3A4 inhibitor (eg, ketoconazole) within 14 days prior to treatment administration
Concurrent use of a strong CYP2C8 inhibitor (eg, gemfibrozil) or inducer (eg, rifampin) within 14 days prior to treatment administration
Concurrent use of an oral medication with a narrow therapeutic index known to be a P-glycoprotein (P-gp) substrate within 24 hours prior to treatment administration
Concurrent use of a medication known to be a strong P-gp inhibitor or inducer within 14 days prior to treatment administration
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
Other severe acute or chronic medical (including bone marrow suppressive diseases) or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation, impede the ability of the subject to complete all protocol-specified activities, or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for this study
The Estimated Number of Participants
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Taiwan
18 participants
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Global
43 participants
