A Pilot Study of Oraxol in Subjects with Cutaneous Angiosarcoma

Phase 1

• Conditions: Study of Oraxol in Subjects with Cutaneous Angiosarcoma; MedDRA version: 20.0Level: PTClassification code 10002477Term: Angiosarcoma metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-002085-13-GB
• Lead Sponsor: Athenex, Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-08-07
• Last Update Posted: 9 September 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 43

Inclusion Criteria

Eligible subjects must have/be:

1. 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
2. Age of 18 years or older
3. 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)
4. Subjects who have not received taxanes for the treatment of angiosarcoma
5. Measurable disease per RECIST v.1.1
6. Eastern Cooperative Oncology Group (ECOG) performance status =1
7. 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
8. 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
o absolute neutrophil count (ANC) =1.5 × 109/L
o hemoglobin =9.0 g/dL (<9.0 g/dL is acceptable if it is corrected by transfusion), and
o platelet count =100 × 109/L
• Adequate liver function as evidenced by
o total bilirubin within normal limits
o alanine aminotransferase (ALT) =3×ULN, and aspartate aminotransferase (AST) =3×ULN
o gamma-glutamyl transferase (GGT) =10×ULN, and
o alkaline phosphatase =3×ULN
9. Able to swallow pills whole and retain oral medications
10. 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
11. 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.
12. Life expectancy of at least 3 months, in the opinion of the Investigator
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 23
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion Criteria

Eligible subjects must not have/be:

1. Subjects with metastases outside of local lymph node involvement
2. Concurrent treatment or participation on other therapeutic clinical trial for angiosarcoma. Participation in companion studies sponsored by local institutions, including biological correlates, is permitted.
3. Women who are pregnant or breastfeeding
4. Receipt of systemic cytotoxic therapy, including investigational agents, within 14 days or 5 halflives of the first study dosing day, whichever is longer
5. 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.
6. 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.
7. History of brain involvement with cancer, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease.
8. 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
9. 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.
10. Thrombolytic use (except to maintain IV catheters) within 10 days prior to treatment administration
11. Presence of a malabsorption syndrome or major resection of the stomach or small bowel that could affect the absorption of Oraxol
12. Known active viral or non-viral hepatitis or cirrhosis
13. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
14. Active infection that requires systemic treatment
15. 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
16. Concurrent use of a strong CYP2C8 inhibitor (eg, gemfibrozil) or inducer (eg, rifampin) within
14 days prior to treatment administration
17. 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
18. Concurrent use of a medication known to be a strong P-gp inhibitor or inducer within 14 days prior to treatment administration
19. 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
20. 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified