Clinical Trials /

A Pilot Study of Oraxol in Subjects With Cutaneous Angiosarcoma

NCT03544567

Description:

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.

Related Conditions:
  • Skin Angiosarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Pilot Study of Oraxol in Subjects With Cutaneous Angiosarcoma
  • Official Title: A Pilot Study of Oraxol in Subjects With Cutaneous Angiosarcoma

Clinical Trial IDs

  • ORG STUDY ID: KX-ORAX-010
  • NCT ID: NCT03544567

Conditions

  • Angiosarcoma of Skin

Interventions

DrugSynonymsArms
Oraxoloral HM30181A + oral paclitaxelOraxol

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
OraxolExperimentalOraxol 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.
  • Oraxol

Eligibility 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

        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
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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

Secondary Outcome Measures

Measure:Incidence of Treatment-Emergent Adverse Events
Time Frame:an average of 1 year
Safety Issue:
Description:Overall safety and tolerability of Oraxol in subjects with cutaneous angiosarcoma
Measure:Progression free survival
Time Frame:24 months
Safety Issue:
Description:To determine the progression-free survival (PFS) after initiation of treatment with Oraxol in subjects with cutaneous angiosarcoma
Measure:Overall Survival (OS)
Time Frame:24 months
Safety Issue:
Description:To determine the overall survival (OS) after initiation of treatment with Oraxol in subjects with cutaneous angiosarcoma
Measure:Duration of response
Time Frame:24 months
Safety Issue:
Description:To determine the duration of response in subjects with cutaneous angiosarcoma
Measure:Time to best response
Time Frame:24 months
Safety Issue:
Description:To determine the time to best response in subjects with cutaneous angiosarcoma

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Athenex, Inc.

Last Updated

August 11, 2020