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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)

Primary Purpose

Metastatic Breast Cancer

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Eribulin mesylate
Eribulin mesylate
Eribulin mesylate
Biologic: PEGylated recombinant human hyaluronidase (PEGPH20)
Biologic: PEGylated recombinant human hyaluronidase
Sponsored by
Eisai Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Breast Cancer focused on measuring PEGylated Recombinant Human Hyaluronidase, Eribulin Mesylate, E7389, PEGPH20, Human Epidermal Growth Factor Receptor 2-Negative, High-Hyaluronan

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Eribulin mesylate plus PEGPH20 (Phase 1b)

Eribulin mesylate plus PEGPH20 (Phase 2)

Eribulin mesylate (Phase 2)

Arm Description

Recommended Phase 2 dose (RP2D) will be determined from the below dose levels: Dose level 1: PEGPH20 (3.0 microgram per kilogram (mcg/kg)) followed by eribulin mesylate (1.4 milligrams per square meter (mg/m^2)) or Dose level 0: PEGPH20 (1.6 mcg/kg) followed by eribulin mesylate (1.4 mg/m^2) or Dose level -1: PEGPH20 (1.6 mcg/kg) followed by eribulin mesylate (1.1 mg/m^2) Dose level 1 can be selected as the RP2D if no more than 1 out of 6 participants has a DLT; DLT was only observed from the first treatment cycle; 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. Upon determination of the RP2D, study Phase 1b Expansion Part will proceed to confirm the RP2D, and thereafter Phase 2 part will proceed.

Participants will receive eribulin mesylate and PEGPH20 at the established RP2D level achieved in the Phase 1b.

Participants will receive eribulin mesylate at 1.4 mg/m^2.

Outcomes

Primary Outcome Measures

Phase 1b: Recommended Phase 2 Dose (RP2D) of Eribulin Mesylate in Combination With PEGPH20
The RP2D was the maximum tolerated dose (MTD) or less. The MTD was determined as the dose level (1, 0) at which less than or equal to (<=) 1 of 6 evaluable participants experienced dose limiting toxicity (DLT) within the first 21 days of treatment (end of Cycle 1). Upon determination of RP2D in Cycle 1 of Phase 1b, RP2D was to be confirmed in Phase 1b-expansion Part.
Phase 1b: Recommended Phase 2 Dose (RP2D) of PEGPH20 in Combination With Eribulin Mesylate
The RP2D was the MTD or less. The MTD was determined as the dose level (1, 0) at which <=1 of 6 evaluable participants experienced DLT within the first 21 days of treatment (end of Cycle 1). Upon determination of RP2D in Cycle 1 of Phase 1b, RP2D was to be confirmed in Phase 1b-expansion Part.

Secondary Outcome Measures

Full Information

First Posted
April 26, 2016
Last Updated
June 25, 2020
Sponsor
Eisai Inc.
Collaborators
Halozyme Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT02753595
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)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2020
Overall Recruitment Status
Terminated
Why Stopped
evolving standard of care and difficulties of enrolling participants
Study Start Date
July 13, 2016 (Actual)
Primary Completion Date
August 16, 2019 (Actual)
Study Completion Date
August 16, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eisai Inc.
Collaborators
Halozyme Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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 (RP2D determined dosing). 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Breast Cancer
Keywords
PEGylated Recombinant Human Hyaluronidase, Eribulin Mesylate, E7389, PEGPH20, Human Epidermal Growth Factor Receptor 2-Negative, High-Hyaluronan

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Eribulin mesylate plus PEGPH20 (Phase 1b)
Arm Type
Experimental
Arm Description
Recommended Phase 2 dose (RP2D) will be determined from the below dose levels: Dose level 1: PEGPH20 (3.0 microgram per kilogram (mcg/kg)) followed by eribulin mesylate (1.4 milligrams per square meter (mg/m^2)) or Dose level 0: PEGPH20 (1.6 mcg/kg) followed by eribulin mesylate (1.4 mg/m^2) or Dose level -1: PEGPH20 (1.6 mcg/kg) followed by eribulin mesylate (1.1 mg/m^2) Dose level 1 can be selected as the RP2D if no more than 1 out of 6 participants has a DLT; DLT was only observed from the first treatment cycle; 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. Upon determination of the RP2D, study Phase 1b Expansion Part will proceed to confirm the RP2D, and thereafter Phase 2 part will proceed.
Arm Title
Eribulin mesylate plus PEGPH20 (Phase 2)
Arm Type
Experimental
Arm Description
Participants will receive eribulin mesylate and PEGPH20 at the established RP2D level achieved in the Phase 1b.
Arm Title
Eribulin mesylate (Phase 2)
Arm Type
Experimental
Arm Description
Participants will receive eribulin mesylate at 1.4 mg/m^2.
Intervention Type
Drug
Intervention Name(s)
Eribulin mesylate
Other Intervention Name(s)
E7389
Intervention Description
Eribulin mesylate will be administered at 1.4 mg/m^2 or 1.1 mg/m^2 as intravenous (IV) infusion on Day 1 and 8 of 21-day cycle
Intervention Type
Drug
Intervention Name(s)
Eribulin mesylate
Other Intervention Name(s)
E7389
Intervention Description
Eribulin mesylate will be administered at 1.4 mg/m^2 or 1.1 mg/m^2, depending on RP2D, as IV infusion on Day 1 and 8 of each 21-day cycle
Intervention Type
Drug
Intervention Name(s)
Eribulin mesylate
Other Intervention Name(s)
E7389
Intervention Description
Eribulin mesylate will be administered at 1.4 mg/m^2 as IV infusion on Day 1 and 8 of 21-day cycle
Intervention Type
Other
Intervention Name(s)
Biologic: PEGylated recombinant human hyaluronidase (PEGPH20)
Intervention Description
PEGPH20 will be administered at 3.0 mcg/kg or 1.6 mcg/kg as IV infusion on Day -1 and 7 of 21-day cycle
Intervention Type
Other
Intervention Name(s)
Biologic: PEGylated recombinant human hyaluronidase
Intervention Description
PEGPH20 will be administered at 3.0 mcg/kg or 1.6 mcg/kg, depending on RP2D, as IV infusion on Day -1 and 7 of each 21-day cycle
Primary Outcome Measure Information:
Title
Phase 1b: Recommended Phase 2 Dose (RP2D) of Eribulin Mesylate in Combination With PEGPH20
Description
The RP2D was the maximum tolerated dose (MTD) or less. The MTD was determined as the dose level (1, 0) at which less than or equal to (<=) 1 of 6 evaluable participants experienced dose limiting toxicity (DLT) within the first 21 days of treatment (end of Cycle 1). Upon determination of RP2D in Cycle 1 of Phase 1b, RP2D was to be confirmed in Phase 1b-expansion Part.
Time Frame
Up to Cycle 28 (Cycle Length= 21 days)
Title
Phase 1b: Recommended Phase 2 Dose (RP2D) of PEGPH20 in Combination With Eribulin Mesylate
Description
The RP2D was the MTD or less. The MTD was determined as the dose level (1, 0) at which <=1 of 6 evaluable participants experienced DLT within the first 21 days of treatment (end of Cycle 1). Upon determination of RP2D in Cycle 1 of Phase 1b, RP2D was to be confirmed in Phase 1b-expansion Part.
Time Frame
Up to Cycle 28 (Cycle Length= 21 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Metastatic Her-2- breast cancer Up to 2 prior lines of cytotoxic or targeted anti-cancer therapy for metastatic disease Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 Exclusion Criteria Less than 6 months since prior neoadjuvant/adjuvant chemotherapy 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 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 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 Pregnant or breastfeeding
Facility Information:
City
Whittier
State/Province
California
ZIP/Postal Code
90602
Country
United States
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30318
Country
United States
City
Newnan
State/Province
Georgia
ZIP/Postal Code
30265
Country
United States
City
Anderson
State/Province
Indiana
ZIP/Postal Code
46011
Country
United States
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20817
Country
United States
City
Stony Brook
State/Province
New York
ZIP/Postal Code
11794
Country
United States
City
Kennewick
State/Province
Washington
ZIP/Postal Code
99336
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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)

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