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Study of Eribulin Mesylate in Combination With PEGylated Recombinant Human Hyaluronidase (PEGPH20) Versus Eribulin Mesylate Alone in Subjects With Human Epidermal Growth Factor Receptor 2 (HER2)-Negative, High-Hyaluronan (HA) Metastatic Breast Cancer (MBC)

NCT02753595

Description:

The primary objective for the study is as follows: For the Phase 1b - to determine safety tolerability and recommended Phase 2 dose (RP2D) of eribulin mesylate in combination with PEGylated recombinant human hyaluronidase (PEGPH20) in participants with Human Epidermal Growth Factor Receptor (HER2)-negative metastatic breast cancer (MBC) previously treated with up to two lines of systemic anticancer therapy in the metastatic setting. For the Phase 2 - to evaluate objective response rate (ORR) of eribulin mesylate in combination with PEGPH20 in participants with HER2-negative, High-Hyaluronan (HA)-high, MBC previously treated with up to 2 lines of systemic anticancer therapy in the metastatic setting.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Unknown status

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Eribulin Mesylate in Combination With PEGylated Recombinant Human Hyaluronidase (PEGPH20) Versus Eribulin Mesylate Alone in Subjects With Human Epidermal Growth Factor Receptor 2 (HER2)-Negative, High-Hyaluronan (HA) Metastatic Breast Cancer (MBC)
  • Official Title: A Randomized, Open-label, Multicenter, Phase 1b/2 Study of Eribulin Mesylate in Combination With PEGylated Recombinant Human Hyaluronidase (PEGPH20) Versus Eribulin Mesylate Alone in Subjects With Human Epidermal Growth Factor Receptor 2 (HER2)-Negative, High-Hyaluronan (HA) Metastatic Breast Cancer (MBC)

Clinical Trial IDs

  • ORG STUDY ID: E7389-M000-219
  • NCT ID: NCT02753595

Conditions

  • Metastatic Breast Cancer

Interventions

DrugSynonymsArms
Eribulin mesylateE7389Eribulin mesylate plus PEGPH20 (Phase 1b)
Eribulin mesylateE7389Eribulin mesylate plus PEGPH20 (Phase 2)
Eribulin mesylateE7389Eribulin mesylate (Phase 2)

Purpose

The primary objective for the study is as follows: For the Phase 1b - to determine safety tolerability and recommended Phase 2 dose (RP2D) of eribulin mesylate in combination with PEGylated recombinant human hyaluronidase (PEGPH20) in participants with Human Epidermal Growth Factor Receptor (HER2)-negative metastatic breast cancer (MBC) previously treated with up to two lines of systemic anticancer therapy in the metastatic setting. For the Phase 2 - to evaluate objective response rate (ORR) of eribulin mesylate in combination with PEGPH20 in participants with HER2-negative, High-Hyaluronan (HA)-high, MBC previously treated with up to 2 lines of systemic anticancer therapy in the metastatic setting.

Detailed Description

      Phase 1b will occur in two parts:

      Part 1: Run-in safety cohort(s) (dose levels 1, 0, and -1, as necessary) of 6 participants
      each will be conducted until the RP2D is determined. The purpose of the run-in safety
      cohort(s) is to study the safety of the 2-drug combination and determine a RP2D. Dose
      limiting toxicity (DLT) will be assessed in the first cycle to determine the RP2D of eribulin
      mesylate in combination with PEGPH20.

      Part 2 (Phase 1b "Expansion Part"): A total of 12 additional participants will be enrolled at
      the RP2D determined in Part 1 (using Phase 1b criteria, i.e., participants previously treated
      with up to 2 lines of systemic anticancer therapy) in order to assess the safety profile of
      the combination and identify any potential safety signals and the incidence of thromboembolic
      events in this population.

      In Phase 2, participants will be stratified by triple negative breast cancer (TNBC) status
      and randomized 1:1 to receive eribulin mesylate and PEGPH20 at the established RP2D level or
      eribulin mesylate alone at 1.4 milligrams per square meters (mg/m^2).
    

Trial Arms

NameTypeDescriptionInterventions
Eribulin mesylate plus PEGPH20 (Phase 1b)ExperimentalRecommended Phase 2 dose (RP2D) will be assessed in the below dose levels: RP2D level 1: PEGPH20 (3.0 microgram per killogram (μg/kg)) plus eribulin mesylate (1.4 milligrams per square meter (mg/m2)) or RP2D level 0: PEGPH20 (1.6 μg/kg) plus eribulin mesylate (1.4 mg/m2) or RP2D level -1: PEGPH20 (1.6 μg/kg) plus eribulin mesylate (1.1 mg/m2) Dose level 1 can be selected as the RP2D if no more than 1 out of 6 participants has a DLT; otherwise, Dose level 0 will be assessed in a second cohort of 6 subjects and will be selected as the RP2D if no more than 1 subject has a DLT. Otherwise, Dose level - 1 will be assessed in a third cohort of 6 subjects. If no more than 1 of 6 subjects in this third cohort has a DLT, the Phase 2 part will proceed with dose level -1 as the RP2D. Otherwise, alternative doses will be explored prior to the start of Phase 2.
  • Eribulin mesylate
Eribulin mesylate plus PEGPH20 (Phase 2)ExperimentalParticipants will receive eribulin mesylate and PEGPH20 at the established RP2D level achieved in the Phase 1b.
  • Eribulin mesylate
Eribulin mesylate (Phase 2)ExperimentalParticipants will receive eribulin mesylate at 1.4 mg/m2.
  • Eribulin mesylate

Eligibility Criteria

        Inclusion Criteria

          1. Metastatic Her-2- breast cancer

          2. Up to 2 prior lines of cytotoxic or targeted anti-cancer therapy for metastatic
             disease

          3. Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1

          4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1

        Exclusion Criteria

          1. Less than 6 months since prior neoadjuvant/adjuvant chemotherapy

          2. Known central nervous system (CNS) disease, except for those participants with treated
             brain metastasis who are stable for at least 1 month, having no evidence of
             progression or hemorrhage after treatment and no ongoing requirement for
             corticosteroids, as ascertained by clinical examination and brain imaging (MRI or CT)
             during the screening period

          3. Previous history or current evidence of deep vein thrombosis (DVT), hereditary
             thrombophilic syndromes, pulmonary embolism (PE), cerebral vascular accident (CVA),
             transient ischemic attack (TIA), atrial fibrillation (AF), or active carotid artery
             disease requiring treatment

          4. Treatment with chemotherapy, hormonal, or biological therapy within the previous 3
             weeks, radiation or small molecule targeted therapy within the previous 2 weeks
             preceding informed consent

          5. Pregnant or breastfeeding
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recommended Phase 2 dose (RP2D) of eribulin mesylate in combination with PEGylated recombinant human hyaluronidase (PEGPH20) - Phase 1b
Time Frame:up to 21 days (Cycle 1)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Progression-free survival (PFS) - Phase 2
Time Frame:Up to approximately 36 months
Safety Issue:
Description:
Measure:Overall survival (OS) - Phase 2
Time Frame:Up to approximately 36 months
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Unknown status
Lead Sponsor:Eisai Inc.

Trial Keywords

  • PEGylated Recombinant Human Hyaluronidase
  • Eribulin Mesylate
  • E7389
  • PEGPH20
  • Human Epidermal Growth Factor Receptor 2-Negative
  • High-Hyaluronan

Last Updated

February 26, 2019