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 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: E7389-M000-2192015-004740-19
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 7

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.

Conditions

Metastatic Breast Cancer

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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.

  Up to Cycle 28 (Cycle Length= 21 days)

• 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.

  Up to Cycle 28 (Cycle Length= 21 days)

Study Arms (3)

Eribulin mesylate plus PEGPH20 (Phase 1b)

EXPERIMENTAL

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.

Drug: Eribulin mesylate; Other: Biologic: PEGylated recombinant human hyaluronidase (PEGPH20)

Eribulin mesylate plus PEGPH20 (Phase 2)

EXPERIMENTAL

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

Drug: Eribulin mesylate; Other: Biologic: PEGylated recombinant human hyaluronidase

Eribulin mesylate (Phase 2)

EXPERIMENTAL

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

Drug: Eribulin mesylate

Interventions

Eribulin mesylate DRUG

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

Also known as: E7389

Eribulin mesylate plus PEGPH20 (Phase 1b)

Biologic: PEGylated recombinant human hyaluronidase (PEGPH20) OTHER

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

Eribulin mesylate plus PEGPH20 (Phase 1b)

Biologic: PEGylated recombinant human hyaluronidase OTHER

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

Eribulin mesylate plus PEGPH20 (Phase 2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eisai Inc.: lead
• Halozyme Therapeutics: collaborator

Study Sites (7)

Unknown Facility

Whittier, California, 90602, United States

Location

Unknown Facility

Atlanta, Georgia, 30318, United States

Location

Unknown Facility

Newnan, Georgia, 30265, United States

Location

Unknown Facility

Anderson, Indiana, 46011, United States

Location

Unknown Facility

Bethesda, Maryland, 20817, United States

Location

Unknown Facility

Stony Brook, New York, 11794, United States

Location

Unknown Facility

Kennewick, Washington, 99336, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

eribulin; PEGPH20

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

The outcome measures assessing efficacy are not applicable for results disclosure due to immaturity of the data, as the study was terminated early in Phase 1b-Expansion part and prior to the initiation and enrollment of Phase 2.

Results Point of Contact

• Title: Eisai Medical Information
• Organization: Eisai, Inc.

esi_oncmedinfo@eisai.com

1-888-274-2378

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2016
• First Posted: April 28, 2016
• Study Start: July 13, 2016
• Primary Completion: August 16, 2019
• Study Completion: August 16, 2019
• Last Updated: July 13, 2020
• Results First Posted: July 13, 2020

Record last verified: 2020-06

Locations

US (7)