Clinical Trials /

Evaluate Eribulin ORA in Subjects With Solid Tumors

NCT04013217

Description:

This is a nonrandomized, open-label, dosed escalation, safety activity, and PK study to determine the MTD and optimal dosing regimen of Eribulin ORA.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Evaluate Eribulin ORA in Subjects With Solid Tumors
  • Official Title: A Phase I Study With Expansion Cohorts to Assess the Safety, Tolerability, and Activity of Eribulin ORA in Subjects With Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: ATX-ERB-001
  • NCT ID: NCT04013217

Conditions

  • Solid Tumor

Purpose

This is a nonrandomized, open-label, dosed escalation, safety activity, and PK study to determine the MTD and optimal dosing regimen of Eribulin ORA.

Detailed Description

      This is a multicenter, open-label safety, tolerability, pharmacokinetic, and activity study.
      Eligible subjects will be adults with advanced solid tumors.

      Groups of 3 to 6 subjects will receive a single dose of Eribulin ORA on Day 1 and Day 8 of a
      21 day cycle and will be followed for toxicity. If non linearity in PK is observed,
      additional subjects will be added with study drug administered on Day 1 and 8 once every
      three weeks cycle. Subjects who tolerate the study drug and have stable disease or better
      response will be eligible to receive ongoing treatment.
    

Trial Arms

NameTypeDescriptionInterventions
Eribulin ORAExperimentalTo determine the MTD of Eribulin ORA (oral eribulin mesylate and HM30181A) when administered on Day 1 and Day 8 of a 3 weeks cycle.

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Able to understand and sign an informed consent form (ICF)
    
              2. Male and female adults, ≥18 years of age
    
              3. Histologically or cytologically confirmed solid tumor that is metastatic or
                 unresectable and for which standard curative or palliative measures do not exist or
                 are no longer effective; subjects enrolling in the dose expansion cohort must have
                 breast cancer or liposarcoma.
    
              4. Must have at least one measurable site of disease as defined as per RECIST v1.1
                 criteria (dose expansion) or evaluable disease (dose escalation only)
    
              5. Eastern Cooperative Oncology Group (ECOG)2 Performance Status ≤1
    
              6. Adequate hematologic status as demonstrated by not requiring transfusion support or
                 granulocyte-colony stimulating factor (G-CSF) to maintain:
    
                   -  Absolute neutrophil count (ANC) ≥1.5 x 109/L
    
                   -  Platelet count ≥100 x 109/L
    
                   -  Hemoglobin ≥9.0 g/dL
    
              7. Adequate liver function as demonstrated by:
    
                   -  Total and direct bilirubin within normal range
    
                   -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 upper
                      limit of normal (ULN)
    
                   -  Gamma-glutamyl transferase (GGT) ≤5 x ULN
    
                   -  Alkaline phosphatase ≤3 x ULN or ≤5 x ULN if bone or liver metastasis is present
    
              8. Serum creatinine ≤1.5 x ULN, or estimated creatinine clearance ≥50 mL/min according to
                 the Cockcroft-Gault equation
    
              9. Prothrombin time (PT)/international normalized ratio (INR)/partial thromboplastin time
                 (PTT) ≤1.5 x ULN OR if a subject is receiving anticoagulant therapy and PT or PTT is
                 within therapeutic range of intended use of coagulants for 7 days prior to receiving
                 study treatment
    
             10. Subjects receiving warfarin who are otherwise eligible and who may be appropriately
                 managed with low molecular weight heparin, in the opinion of the Investigator, may be
                 enrolled in the study provided they are switched to low molecular weight heparin at
                 least 7 days prior to receiving study treatment.
    
             11. Willing and able to comply with scheduled visits, treatment plan and laboratory tests
    
             12. No concurrent malignancy except curatively treated basal or squamous cell carcinoma of
                 the skin or carcinoma in situ of the cervix, breast, or bladder
    
             13. Men who are sterile (including vasectomy confirmed by post vasectomy semen analysis)
                 OR agree to use a condom with spermicide and to not donate sperm during the study and
                 for at least 90 days following last dose of Eribulin ORA
    
             14. Female subjects must be postmenopausal (>12 months without menses) or surgically
                 sterile (ie, by hysterectomy and/or bilateral oophorectomy) or must be using highly
                 effective contraception (ie, oral contraceptives, intrauterine device, double barrier
                 method of condom and spermicide) and agree to continue use of contraception for 90
                 days after their last dose of assigned study treatment.
    
             15. Subjects who are of childbearing potential must have a negative serum pregnancy test
                 at Screening and within 72 hours before the first dose.
    
            Exclusion Criteria:
    
              1. Subjects who have received recent anti-cancer therapy defined by:
    
                   -  Chemotherapy, immunotherapy, hormonal therapy and monoclonal antibodies (but
                      excluding nitrosurea, mitomycin-C, targeted therapy) ≤28 days prior to starting
                      study drug, or who have not recovered from side effects of such therapy to Grade
                      1. Subjects receiving luteinizing hormone-releasing hormone (LHRH) agonists may
                      be considered for enrollment after discussion with the Sponsor.
    
                   -  Last administration of nitrosurea or mitomycin-C ≤42 days prior to starting study
                      drug, or who have not recovered from the side effects of such therapy to Grade 1
    
                   -  Targeted therapy (eg, sunitinib, sorafenib, pazopanib) ≤14 days prior to starting
                      study drug, or who have not recovered from the side effects of such therapy to
                      Grade 1; or
    
                   -  Radiotherapy ≤28 days prior to starting study drug, or ≤14 days prior to starting
                      study drug in the case of localized radiotherapy (eg, for analgesic purpose or
                      for lytic lesions at risk of fracture), or who have not recovered from
                      radiotherapy toxicities to Grade 1.
    
              2. Subject who have impairment of gastrointestinal (GI) function or GI disease that may
                 significantly alter the absorption of study drugs (including gastric bypass surgery
                 and total gastrectomy).
    
              3. Subjects who have undergone major surgery (eg, intra-thoracic, intra-abdominal or
                 intrapelvic), open biopsy or significant traumatic injury ≤28 days prior to starting
                 study treatment, or subjects who have had minor procedures, percutaneous biopsies or
                 placement of vascular access device ≤7 days prior to starting study drug, or who have
                 not recovered from side effects of such procedure or injury
    
              4. Subjects with congenital long QT syndrome
    
              5. Uncontrolled concurrent illness, including but not limited to ongoing or active
                 serious infection requiring systemic antimicrobials (within 14 days prior to first
                 dose), uncontrolled arterial hypertension (>160/100 mm/Hg on antihypertensive
                 medications), chronic pulmonary disease requiring oxygen, known bleeding disorders,
                 uncontrolled endocrine diseases, altered mental status or psychiatric illness/social
                 situations that would limit compliance with protocol requirements.
    
              6. Known or suspected diagnosis of human immunodeficiency virus (HIV) or chronic active
                 Hepatitis B or C, or cirrhosis.
    
              7. Symptomatic or uncontrolled brain metastases requiring current treatment (less than 28
                 days from last cranial radiation or 28 days from last steroids use).
    
              8. Impaired cardiac function or clinically significant cardiac disease including the
                 following:
    
                   -  Clinically significant arrhythmias (except chronic well controlled atrial
                      fibrillation)
    
                   -  New York Heart Association (NYHA) Class III or IV congestive heart failure
    
                   -  Unstable angina pectoris within the last 6 months
    
                   -  Myocardial infarction within the last 6 months
    
              9. Subjects with a healing or open wound
    
             10. Lack of recovery of prior AEs to Grade ≤1 severity (National Cancer Institute [NCI]
                 Common Terminology Criteria for Adverse Events [CTCAE] v4.03)3 (except alopecia or
                 lymphopenia) due to medications administered prior to the first dose of the trial
                 drugs.
    
             11. Any other condition or finding (including social situation) that in the opinion of the
                 Investigator may render the patient at excessive risk for treatment complications or
                 may not be able to provide evaluable outcome information.
    
             12. Pregnant or breast-feeding women
    
             13. Known allergy to any of the formulation components of Eribulin ORA
    
             14. Currently taking following prohibited concomitant medication:
    
                   -  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
    
                   -  Medication known to be strong P-gp inhibitors or inducers. Subjects who are
                      taking such medications but who are otherwise eligible may be enrolled if they
                      discontinue the medication 7 days before dosing and remain off that medication
                      during treatment with Eribulin ORA.
    
                   -  An oral medication with a narrow therapeutic index known to be a P-gp substrate
                      (eg, digoxin, dabigatran, colchicine) within 1 day prior to start of Eribulin ORA
                      dosing in the study
    
                   -  Drugs known to prolong the QT interval, including Class Ia and III
                      antiarrhythmics
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Dose Escalation: Maximum Tolerated Dose
    Time Frame:3 weeks
    Safety Issue:
    Description:Occurrence of Dose-limiting toxicity (DLT) in all patients who received at lest one dose of Eribulin ORA.

    Secondary Outcome Measures

    Measure:Dose Escalation: Safety
    Time Frame:Up to 24 months
    Safety Issue:
    Description:Occurrence of adverse events in all patients who signed the informed consent .
    Measure:Dose Escalation: Bioavailability
    Time Frame:Up to 24 months
    Safety Issue:
    Description:Pharmacokinetic analysis of Area Under the Curve (AUC) will be done to determine bioavailability of Eribulin IV or Eribulin Ora in all patients who received at least one dose of Eribulin Ora
    Measure:Dose Escalation: Tumor Response
    Time Frame:up to 24 months
    Safety Issue:
    Description:Evaluate objective tumor response rate for confirmed Complete Response in all patients who receive at lease one dose of Eribulin IV or Eribulin Ora
    Measure:Dose Escalation: Tumor Response
    Time Frame:up to 24 months
    Safety Issue:
    Description:Evaluate objective tumor response rate for confirmed Partial Response in all patients who receive at lease one dose of Eribulin IV or Eribulin ORA
    Measure:Dose Escalation: Tumor Response
    Time Frame:up to 24 months
    Safety Issue:
    Description:Evaluate object tumor response rate for confirmed Stable Disease in all patients who receive at lease one dose of Eribulin IV or Eribulin Ora
    Measure:Dose Escalation: Tumor Response
    Time Frame:up to 24 months
    Safety Issue:
    Description:Evaluate objective tumor response rate for Progression of Disease in all patients who receive at lease one dose of Eribulin IV or Eribulin ORA
    Measure:Dose Expansion: Tumor Response
    Time Frame:up to 24 months
    Safety Issue:
    Description:Evaluate objective tumor response rate for Complete Response in all patients who receive at lease one dose of Eribulin ORA
    Measure:Dose Expansion: Tumor Response
    Time Frame:up to 24 months
    Safety Issue:
    Description:Evaluate objective tumor response rate for Partial Response in all patients who receive at lease one dose of Eribulin ora
    Measure:Dose Expansion: Tumor Response
    Time Frame:up to 24 months
    Safety Issue:
    Description:Evaluate objective tumor response rate for Stable Disease in all patients who receive at lease one dose of Eribulin ora
    Measure:Dose Expansion: Tumor Response
    Time Frame:up to 24 months
    Safety Issue:
    Description:Evaluate object tumor response rate for Progression of Disease in all patients who receive at lease one dose of Eribulin ORA
    Measure:Dose Escalation: Bioavailability
    Time Frame:up to 24 months
    Safety Issue:
    Description:Pharmacokinetic analysis of Time to Maximum Effect (Tmax), will be done to determine bioavailability of Eribulin IV or Eribulin Ora in all patients who received at least one dose of Eribulin Ora
    Measure:Dose Escalation: Bioavailability
    Time Frame:up to 24 months
    Safety Issue:
    Description:Pharmacokinetic analysis of Peak Plasma Concentration (Cmax) will be done to determine bioavailability of Eribulin IV or Eribulin Ora in all patients who received at least one dose of Eribulin Ora

    Details

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

    Last Updated

    August 11, 2020