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Trial record 3 of 12 for:    pegph20

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)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by Eisai Inc.
Sponsor:
Collaborator:
Halozyme Therapeutics
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT02753595
First received: April 26, 2016
Last updated: September 14, 2016
Last verified: August 2016
  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 0 to 1 line 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 0 to 1 line of systemic anticancer therapy in the metastatic setting.


Condition Intervention Phase
Metastatic Breast Cancer
Drug: Eribulin mesylate
Other: Biologic: PEGylated recombinant human hyaluronidase (PEGPH20)
Other: Biologic: PEGylated recombinant human hyaluronidase
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
  • Objective response rate (ORR) - Phase 2 [ Time Frame: Up to approximately 30 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival (PFS) - Phase 2 [ Time Frame: Up to approximately 30 months ] [ Designated as safety issue: No ]
  • Overall survival (OS) - Phase 2 [ Time Frame: Up to approximately 30 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 96
Study Start Date: June 2016
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Eribulin mesylate plus PEGPH20 (Phase 1b)

Recommended 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.

Drug: Eribulin mesylate
Eribulin mesylate will be administered at 1.4 mg/m2 or 1.1 mg/m2 as intravenous (IV) infusion on Day 1 and 8 of 21-day cycle
Other Name: E7389
Other: Biologic: PEGylated recombinant human hyaluronidase (PEGPH20)
PEGPH20 will be administered at 3.0 μg/kg or 1.6 μg/kg as IV infusion on Day -1 and 7 of 21-day cycle
Experimental: Eribulin mesylate plus PEGPH20 (Phase 2)
Participants will receive eribulin mesylate and PEGPH20 at the established RP2D level achieved in the Phase 1b.
Drug: Eribulin mesylate
Eribulin mesylate will be administered at 1.4 mg/m2 or 1.1 mg/m2, depending on RP2D, as IV infusion on Day 1 and 8 of each 21-day cycle
Other Name: E7389
Other: Biologic: PEGylated recombinant human hyaluronidase
PEGPH20 will be administered at 3.0 μg/kg or 1.6 μg/kg, depending on RP2D, as IV infusion on Day -1 and 7 of each 21-day cycle
Experimental: Eribulin mesylate (Phase 2)
Participants will receive eribulin mesylate at 1.4 mg/m2.
Drug: Eribulin mesylate
Eribulin mesylate will be administered at 1.4 mg/m2 as IV infusion on Day 1 and 8 of 21-day cycle
Other Name: E7389

Detailed Description:
The Phase 1b part will have dose limiting toxicity (DLT) assessed in the first cycle to determine the RP2D of eribulin mesylate in combination with PEGPH20. In the Phase 2 part, 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 milligram per square meter (mg/m2).
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Histological adenocarcinoma of the breast.
  2. Females or males, aged ≥18 years at the time of signing the informed consent form (ICF).
  3. Human epidermal growth factor receptor 2-negative (defined as immunohistochemistry (IHC) <2+ or fluorescence in situ hybridization (FISH) negative) breast cancer previously treated with 0 to 1 line of systemic anticancer therapy (cytotoxic or targeted anticancer agents) in the metastatic setting. Hormonal therapy and bone metastases treatment (eg, bisphosphonates, denosumab, etc.) are not considered forms of systemic anticancer therapy.
  4. Archived tissue sample or new biopsy sample:

    Metastatic breast cancer tissue with High-Hyaluronan (HA)-high levels based on available tumor tissue in formaldehyde fixed-paraffin embedded (FFPE) block or minimum of 5 (10 preferred) unstained core biopsy slides that meet specific tissue sample requirements. Fine needle aspirates (FNA) or brushing biopsies will not be acceptable.

    (NOTE: HA status is not a requirement for enrollment in Phase 1b).

  5. Phase 2 participants must be determined to be HA-high based on a clinical trial assay from a central laboratory (details in a separate Laboratory Manual). Tumor samples must meet the requirements noted in the previous criteria (see Study Laboratory Manual).
  6. Presence of measureable disease meeting the following criteria:

    1. At least 1 lesion of ≥10 mm in long axis diameter for non-lymph nodes or ≥15 mm in short axis diameter for lymph nodes that is serially measurable according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) using computerized tomography (CT) or magnetic resonance imaging (MRI).
    2. Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies such as radiofrequency (RF) ablation must show evidence of subsequent progressive disease (substantial size increase of ≥20%) to be deemed a target lesion.
  7. Life expectancy of ≥3 months.
  8. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
  9. Adequate renal function as evidenced by serum creatinine ≤1.5 milligram/deciliter (mg/dL) or calculated creatinine clearance ≥50 mL/minute according to the Cockcroft and Gault formula.
  10. Adequate bone marrow function, defined as:

    1. Absolute neutrophil count (ANC) ≥1.5 × 10^9/liter (L) and
    2. Hemoglobin (Hgb) ≥9.0 gram/deciliter (g/dL); can be corrected by growth factor or transfusion and
    3. Platelet count ≥100 × 10^9/L.
  11. Adequate liver function, defined as:

    1. Total bilirubin ≤1.5 × upper limit of normal (ULN), except for unconjugated hyperbilirubinemia or Gilbert's syndrome.
    2. Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤3 × ULN (≤5 × ULN if participant has liver metastases). If ALP is >3 × ULN (in the absence of liver metastases) or >5 × ULN (in the presence of liver metastases) and participants are also known to have bone metastases, the liver specific ALP must be separated from the total and used to assess the liver function instead of the total ALP.
  12. Willing and able to comply with all aspects of the treatment protocol.
  13. Provide written informed consent.

Exclusion Criteria

  1. Previous treatment with eribulin mesylate or any hyaluronidase agent.
  2. Less than 6 months since prior neoadjuvant/adjuvant chemotherapy.
  3. Intolerant of dexamethasone as determined by the investigator.
  4. Active uncontrolled bacterial, viral, or fungal infection requiring systemic therapy.
  5. Previous history or current evidence of deep vein thrombosis (DVT), hereditary thrombophilic syndromes, pulmonary embolism (PE), cerebral vascular attack (CVA), transient ischemic attack (TIA), or active carotid artery disease requiring treatment.
  6. Current enrollment in another interventional clinical study or used any investigational drug or device within the past 28 days preceding informed consent.
  7. Treatment with hormonal or biological therapy within the previous 3 weeks, radiation or small molecule targeted therapy within the previous 2 weeks.
  8. 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.
  9. Known history of human immunodeficiency virus (HIV) positive.
  10. Known active hepatitis B (eg, HBsAg reactive) or hepatitis C (eg, Hepatitis C virus (HCV) ribonucleic acid (RNA) detected).
  11. Existing anticancer treatment-related toxicities of Grades ≥2 (except for alopecia and Grade 2 sensory neuropathy) according to Common Terminology Criteria for Adverse Events (CTCAE v4.03).
  12. Other active malignancy (except definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix or bladder) within past 24 months.
  13. Significant cardiovascular impairment: History of (a) congestive heart failure greater than New York Heart Association (NYHA) Class II, (b) unstable angina, (c) myocardial infarction (d) stroke or (e) cardiac arrhythmia associated with hemodynamic instability within 6 months of the first dose of study drug.
  14. Clinically significant electrocardiogram (ECG) abnormality, including a marked Baseline prolonged QT/QTc (QT interval/corrected QT interval), eg, a repeated demonstration of a corrected QT (QTc) interval >500 millisecond (ms)).
  15. Pulmonary lymphangitic spread.
  16. Scheduled for major surgery during the study.
  17. Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin (ß-hCG) (or human chorionic gonadotropin (hCG)) test with a minimum sensitivity of 25 IU/L or equivalent units of ß-hCG or hCG). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
  18. Females of childbearing potential who:

    • Do not agree to use a highly effective method of contraception (eg, total abstinence if it is their preferred and usual lifestyle, an intrauterine device, a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) within 30 days before study entry and throughout the entire study period or for 28 days after study drug discontinuation.
    • Are currently totally abstinent (as their preferred and usual lifestyle), and who do not agree to continue to be totally abstinent during the study period or for 28 days after study drug discontinuation.
    • Are using hormonal contraceptives but are not on a stable dose of the same hormonal contraceptive product for at least 4 weeks before dosing and who do not agree to use the same contraceptive during the study or for 28 days after study drug discontinuation.
    • (NOTE: All females will be considered to be of childbearing potential unless they are postmenopausal [amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause] or have been sterilized surgically [ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing]).
  19. Males who have not had a successful vasectomy (confirmed azoospermia) or they and their female partners do not meet the criteria above (ie, not of childbearing potential or using effective contraception throughout the study period or for 28 days after study drug discontinuation). No sperm donation is allowed during the study period or for 28 days after study drug discontinuation.
  20. Known intolerance to the study drugs or any of the excipients.
  21. Known allergy to hyaluronidase.
  22. History of concomitant medical conditions or infectious diseases that, in the opinion of the investigator, would compromise the participant's ability to safely complete the study.
  23. The investigator's belief that the participant is medically unfit to receive eribulin mesylate and PEGPH20 or unsuitable for any other reason.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02753595

Contacts
Contact: Eisai Medical Services 1-888-422-4743

Locations
United States, Georgia
Recruiting
Atlanta, Georgia, United States
United States, Indiana
Recruiting
Anderson, Indiana, United States
United States, Maryland
Not yet recruiting
Bethesda, Maryland, United States
United States, New York
Not yet recruiting
Stony Brook, New York, United States
Sponsors and Collaborators
Eisai Inc.
Halozyme Therapeutics
  More Information

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT02753595     History of Changes
Other Study ID Numbers: E7389-M000-219 
Study First Received: April 26, 2016
Last Updated: September 14, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Eisai Inc.:
PEGylated Recombinant Human Hyaluronidase
Eribulin Mesylate
E7389
PEGPH20
Human Epidermal Growth Factor Receptor 2-Negative
High-Hyaluronan

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Mitogens
Hyaluronic Acid
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Viscosupplements
Protective Agents

ClinicalTrials.gov processed this record on September 23, 2016