Trial of H3B-6545, in Women With Locally Advanced or Metastatic Estrogen Receptor-positive, HER2 Negative Breast Cancer

NCT ID: NCT03250676

Last Updated: 2025-02-25

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

151 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-08-23

Study Completion Date

2023-10-26

Brief Summary

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The primary purpose of phase 1 portion of this study is to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of H3B-6545 in women with locally advanced or metastatic estrogen receptor (ER)-positive, human epidermal growth factor 2 (HER2)-negative breast cancer.

The primary purpose of phase 2 portion of this study is to estimate the efficacy of H3B-6545 in terms of best overall response rate, duration of response (DoR), clinical benefit rate (CBR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) in all participants with ER-positive, HER2-negative breast cancer and in those with and without ER alpha mutation (including a clonal estrogen receptor 1 gene \[ESR1\] Y537S mutation).

Detailed Description

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Conditions

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Breast Neoplasms Breast Cancer Estrogen-receptor Positive Breast Cancer Cancer, Breast Breast Cancer Female Breast Adenocarcinoma Estrogen Receptor Positive Tumor ER Positive

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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H3B-6545 Arm 1: Dose escalation

Group Type EXPERIMENTAL

H3B-6545

Intervention Type DRUG

Oral capsules by mouth once daily

H3B-6545 Arm 2: Phase 2

Group Type EXPERIMENTAL

H3B-6545

Intervention Type DRUG

Oral capsules by mouth once daily

Interventions

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H3B-6545

Oral capsules by mouth once daily

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Pre- or post-menopausal women.
2. ER-positive, HER2-negative breast cancer that is advanced or metastatic.
3. Progressed on prior therapy. Multiple prior lines of therapy allowed in Phase 1 and 2. Participants under amendment 6 (or subsequent amendments) must have received prior cyclin-dependent kinase (CDK4/6) inhibitor therapy. Up to one prior chemotherapy in the metastatic setting is allowed.
4. A recent archival tumor tissue obtained within 6 months prior to enrollment or a fresh tumor biopsy must be provided. A second biopsy after initiating trial therapy is not required.
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
6. Adequate bone marrow and organ function.
7. Participants under amendment 6 (or subsequent amendments) must have measurable disease at baseline as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
8. Participants under amendment 6 (or subsequent amendments) must have ESR1 Y537S mutation in absence of ESR1 D538G mutation as per the results of a central laboratory from a Nucleic Acids Whole Blood sample.

Exclusion Criteria

1. Participants must have at least one measurable lesion.
2. Participant with inflammatory breast cancer.
3. Participant has received more than one prior chemotherapy regimen for metastatic disease (Phase 2 only).
4. Females of childbearing potential who are unable or unwilling to follow adequate contraceptive measures.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Eisai Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Western Regional Medical Center, Inc., DBA Cancer Treatment Centers of America, Phoenix

Goodyear, Arizona, United States

Site Status

University of California Los Angeles

Los Angeles, California, United States

Site Status

University of California San Francisco

San Francisco, California, United States

Site Status

University of Colorado - Cancer Center

Aurora, Colorado, United States

Site Status

Holy Cross Hospital Inc

Fort Lauderdale, Florida, United States

Site Status

Florida Cancer Specialists South

Fort Myers, Florida, United States

Site Status

Florida Cancer Specialists and Research Institute

Sarasota, Florida, United States

Site Status

Florida Cancer Specialists North

St. Petersburg, Florida, United States

Site Status

Southeastern Regional Medical Center, Inc., DBA Cancer Treatment Centers of America, Atlanta

Newnan, Georgia, United States

Site Status

Carle Cancer Center

Urbana, Illinois, United States

Site Status

Midwestern Regional Medical Center, Inc., DBA Cancer Treatment Centers of Americal, Chicago

Zion, Illinois, United States

Site Status

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Saint Luke's Cancer Institute

Kansas City, Missouri, United States

Site Status

Research Medical Center

Kansas City, Missouri, United States

Site Status

Comprehensive Cancer Center of Nevada

Las Vegas, Nevada, United States

Site Status

University of North Carolina

Chapel Hill, North Carolina, United States

Site Status

Tennessee Oncology

Nashville, Tennessee, United States

Site Status

Parkland Health and Hospital System

Dallas, Texas, United States

Site Status

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status

Tyler Oncology/Oncology PA

Tyler, Texas, United States

Site Status

Huntsman Cancer Institute at The University of Utah

Salt Lake City, Utah, United States

Site Status

Edog - Ico - Ppds

Angers, , France

Site Status

Hopital Jean Minjoz

Besançon, , France

Site Status

Centre Jean Perrin

Clermont-Ferrand, , France

Site Status

Centre Oscar Lambret

Lille, , France

Site Status

Hôpital Saint Louis

Paris, , France

Site Status

Hôpital de la Pitié Salpétrière

Paris, , France

Site Status

EDOG - Centre Eugene Marquis Centre Regional de Lutte Contre Le Cancer - PPDS

Rennes, , France

Site Status

EDOG Institut de Cancerologie de l'Ouest - PPDS

Saint-Herblain, , France

Site Status

Institut de Cancérologie Strasbourg Europe

Strasbourg, , France

Site Status

Institut Gustave Roussy

Villejuif, , France

Site Status

The Royal Marsden NHS Foundation Trust

Chelsea, London, United Kingdom

Site Status

Velindre Cancer Centre

Cardiff, , United Kingdom

Site Status

Barts Health NHS Trust

London, , United Kingdom

Site Status

Sarah Cannon Research Institute

London, , United Kingdom

Site Status

Christie Hospital

Manchester, , United Kingdom

Site Status

The Royal Marsden NHS Foundation Trust

Sutton, , United Kingdom

Site Status

Countries

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United States France United Kingdom

References

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Furman C, Puyang X, Zhang Z, Wu ZJ, Banka D, Aithal KB, Albacker LA, Hao MH, Irwin S, Kim A, Montesion M, Moriarty AD, Murugesan K, Nguyen TV, Rimkunas V, Sahmoud T, Wick MJ, Yao S, Zhang X, Zeng H, Vaillancourt FH, Bolduc DM, Larsen N, Zheng GZ, Prajapati S, Zhu P, Korpal M. Covalent ERalpha Antagonist H3B-6545 Demonstrates Encouraging Preclinical Activity in Therapy-Resistant Breast Cancer. Mol Cancer Ther. 2022 Jun 1;21(6):890-902. doi: 10.1158/1535-7163.MCT-21-0378.

Reference Type DERIVED
PMID: 35642432 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2018-000570-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

H3B-6545-A001-101

Identifier Type: -

Identifier Source: org_study_id

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