A Study of Oraxol in Subjects With Cutaneous Angiosarcoma

A Phase 2 Study of Oraxol in Subjects With Cutaneous Angiosarcoma

This is a non-blinded, multi-center, open-label, phase 2 study to evaluate the activity, safety, and tolerability of Oraxol in subjects with cutaneous angiosarcoma.

Study Overview

• Status: Completed
• Conditions: Angiosarcoma of Skin
• Intervention / Treatment: Drug: Oraxol

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Prince of Wales Hospital, Shatin
• Taiwan
  • Taipei City, Taiwan
    • National Taiwan University Hospital
  • Taipei City, Taiwan
    • Taipei Veterans General Hosptial
• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden NHS Foundation Trust
  • London, United Kingdom, NW1 2PG
    • University College London Hospitals Nhs Foundation Trust
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust, Manchester
• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Texas
    • Dallas, Texas, United States, 75251
      • Texas Oncology
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington/Fred Hutchinson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Oraxol; Oraxol will be administered once daily for 3 consecutive days every week 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; additional doses of Oraxol may be administered from Week 26 onwards. Subjects may receive Oraxol until they meet 1 of the criteria for withdrawal from the study.

Drug: Oraxol; oral paclitaxel will be supplied in capsules and oral HM30181A-US in tablets; Other Names: oral HM30181A + oral paclitaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate	To determine the response rate 6 months after initiation of treatment with Oraxol in subjects with cutaneous angiosarcoma	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events	Overall safety and tolerability of Oraxol in subjects with cutaneous angiosarcoma	an average of 1 year
Progression free survival	To determine the progression-free survival (PFS) after initiation of treatment with Oraxol in subjects with cutaneous angiosarcoma	36 months
Overall Survival (OS)	To determine the overall survival (OS) after initiation of treatment with Oraxol in subjects with cutaneous angiosarcoma	36 months
Duration of response	To determine the duration of response in subjects with cutaneous angiosarcoma	36 months
Time to best response	To determine the time to best response in subjects with cutaneous angiosarcoma	an average of 1 year
Progression Free Rate	To determine the progression free rate at 6 months	6 months

Collaborators and Investigators

• Sponsor: Athenex, Inc.
• Investigators: Study Director: David Cutler, MD, Athenex, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2018
• Primary Completion (Actual): May 12, 2023
• Study Completion (Actual): May 12, 2023

Study Registration Dates

• First Submitted: April 5, 2018
• First Submitted That Met QC Criteria: May 31, 2018
• First Posted (Actual): June 4, 2018

Study Record Updates

• Last Update Posted (Actual): May 19, 2023
• Last Update Submitted That Met QC Criteria: May 18, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neoplasms, Vascular Tissue; Hemangiosarcoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: KX-ORAX-010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No