Clinical Trials /

Study of H3B-6545 in Japanese Women With Estrogen Receptor (ER)-Positive, Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer

NCT04568902

Description:

The purpose of study is to determine tolerability and safety profile of H3B-6545 in Japanese women with ER-positive, HER2-negative breast cancer, and also to confirm the dose applicability to Japanese.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of H3B-6545 in Japanese Women With Estrogen Receptor (ER)-Positive, Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer
  • Official Title: A Phase 1 Study of H3B-6545 in Japanese Women With Estrogen Receptor-positive, HER2 Negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: H3B-6545-J081-103
  • NCT ID: NCT04568902

Conditions

  • Breast Neoplasms

Interventions

DrugSynonymsArms
H3B-6545H3B-6545 300 mg

Purpose

The purpose of study is to determine tolerability and safety profile of H3B-6545 in Japanese women with ER-positive, HER2-negative breast cancer, and also to confirm the dose applicability to Japanese.

Trial Arms

NameTypeDescriptionInterventions
H3B-6545 300 mgExperimentalParticipants will receive H3B-6545 300 milligram (mg) tablets, orally, once daily in 28 days cycle.
  • H3B-6545
H3B-6545 450 mgExperimentalParticipants will receive H3B-6545 450 mg tablets, orally, once daily in 28 days cycle.
  • H3B-6545

Eligibility Criteria

        Inclusion Criteria:

          1. Participant has a histologically and/or cytologically confirmed diagnosis of
             ER-positive, HER2-negative breast cancer.

             Note: Status of ER and HER2 should be diagnosed by method approved by regulatory
             authority

          2. Only females, age greater than or equal to (>=) 20 years at the time of informed
             consent.

          3. Prior therapy for breast cancer in the adjuvant and/or advanced/metastatic setting
             must have included a minimum of:

               1. two prior hormonal therapies, or

               2. one prior hormonal therapy and one prior chemotherapy regimen, or

               3. one prior hormonal therapy and a cyclin-dependent kinase (CDK4/6) inhibitor.

          4. Participant has an ECOG-PS of 0 or 1.

          5. Participant has adequate bone marrow and organ function, as defined by the following
             laboratory values:

               -  Absolute neutrophil count (ANC) >=1.5*10˄9/liter (L).

               -  Platelets >=100*10˄9/L.

               -  Hemoglobin >=9.0 gram per deciliter (g/dL).

               -  Potassium, sodium, calcium (corrected for serum albumin) and magnesium less than
                  or equal to (<=) Common Terminology Criteria for Adverse Events (CTCAE) Grade 1.

               -  International normalized ratio (INR) <=1.5.

               -  Serum creatinine <=1.5*upper limit of normal (ULN).

               -  Serum albumin >=3.0 g/dL (>=30 gram per liter [g/L]).

               -  Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) <=3.0*ULN. If
                  the participant has liver metastases, ALT and AST <=5.0*ULN.

               -  Total serum bilirubin less than (<) 1.5*ULN.

          6. Participants who are expected to survive for 3 months or longer after starting
             administration of the investigational drug.

          7. Voluntary agreement to provide written informed consent and the willingness and
             ability to comply with all aspects of the protocol.

        Exclusion Criteria:

          1. Participant with inflammatory breast cancer.

          2. Participant is currently receiving or has received systemic corticosteroids <=2 weeks
             prior to starting study drug, or has not fully recovered from side effects of such
             treatment.

             Note: The following uses of corticosteroids are permitted: single doses, topical
             applications (example- for rash), inhaled sprays (example- for obstructive airways
             diseases), eye drops or local injections (example- intra-articular).

          3. Washout period required from the end of prior treatment to the first administration of
             study drug will be as follows.

               1. Anti-cancer therapy

                    -  Antibody and other study drugs: greater than (>) 4 weeks (however, in the
                       case where the half-life of other study drugs is known and 5*half-lives of
                       that study drug is less than or equal to 4 weeks, participants can be
                       eligible after >=5*half-lives of that study drug has passed).

                    -  Prior chemotherapy (except small-molecule targeted therapy), surgical
                       therapy, radiation therapy: >3 weeks.

                    -  Endocrine therapy, immunotherapy (except antibody drug), small-molecule
                       targeted therapy: >2 weeks.

               2. Supportive therapy • Blood/platelet transfusion, hematopoietic stimulating agent
                  including granulocyte colony-stimulating factor (G-CSF) formulation: >2 weeks.

          4. Participant has active cardiac disease or a history of cardiac dysfunction, including
             any of the following:

               1. History of angina pectoris, symptomatic pericarditis, or myocardial infarction
                  within 12 months prior to study entry.

               2. History of documented congestive heart failure (New York Heart Association [NYHA]
                  functional classification II to IV).

               3. Documented cardiomyopathy.

               4. Participant has a left ventricular ejection fraction (LVEF) <50 percent (%) as
                  determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO).

               5. History of any cardiac arrhythmias, example- ventricular, supraventricular, nodal
                  arrhythmias, or conduction abnormality in the previous 12 months.

               6. Heart Rate <60 beats per minute (bpm) on the screening.

               7. On screening, any of the following cardiac parameters: PR interval >220
                  millisecond (msec), QRS interval >10˄9 msec, or QT interval with Fridericia's
                  correction (QTcF) >450 msec.

               8. Systolic blood pressure (BP) not deemed clinically controlled by the
                  investigator.

          5. Participant has impairment of gastrointestinal (GI) function or GI disease that may
             significantly alter the absorption of H3B-6545.

          6. Participant has a known hypersensitivity to any of the excipients of H3B-6545.

          7. Known to be human immunodeficiency virus (HIV) positive.

          8. Active viral hepatitis (B or C) as demonstrated by positive serology. Participants
             with chronic hepatitis B virus (HBV) infection is on antiviral therapy is eligible.

          9. Participant has any other concurrent severe and/or uncontrolled medical condition that
             would, in the investigator's judgment, contraindicate participant participation in the
             clinical study (example- chronic pancreatitis, thyroid dysfunction etc).

         10. Any adverse event related to previous therapies for breast cancer that has not
             resolved to <=Grade 1 (with exception of the alopecia).

         11. 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). 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.

         12. Women of childbearing potential who don't agree that both the participant and her
             partner will use a medically effective method for contraception (as below) throughout
             the entire study period or for 28 days after study drug discontinuation.

             Note: Condom*, contraceptive sponge**, foam**, jelly**, diaphragm**, intrauterine
             device (IUD) *, or use of oral contraception* from at least 4 weeks before starting
             the study treatment (*Approved drugs or certified medical devices in Japan,
             **Non-approved drugs or certified medical devices in Japan) If a participant is on
             oral contraceptives, they should also be using some additional method.

         13. Alcohol dependency within 6 months before study entry.

         14. Participant has a concurrent malignancy or malignancy within 3 years of enrollment,
             with the exception of adequately treated basal or squamous cell carcinoma,
             non-melanomatous skin cancer, or curatively resected cervical cancer.

         15. Psychological, familial, sociological, or geographical conditions that do not permit
             compliance with the protocol.

         16. Diagnosed with meningeal carcinomatosis. Participants with brain or subdural
             metastases are not eligible, unless they have completed local therapy and have
             discontinued the use of corticosteroids for this indication for at least 4 weeks
             before starting treatment in this study. Any signs (example- radiologic) or symptoms
             of brain metastases must be stable for at least 4 weeks before starting study
             treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with Dose-limiting Toxicities (DLTs)
Time Frame:Up to Cycle 1 (each cycle length is equal to [=] 28 days)
Safety Issue:
Description:Toxicity will be assessed according to National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE), v5.0. DLT is defined as any of the following events occurred within the Cycle 1 of the administration of H3B-6545: Febrile neutropenia, Grade 4 neutropenia that does not resolve to Grade<=2 within 7days, Grade 4 thrombocytopenia, Grade3 thrombocytopenia>=7days or requiring platelet transfusion, Grade3 thrombocytopenia associated with bleeding, Grade4 anemia or Grade3 anemia requiring erythrocyte transfusion; Grade3 or 4 bilirubin increase, AST or ALT>=10*ULN which does not resolve to Grade2 or less within 7days and/or else is clinically significant; Non-hematological toxicities Grade4 and Grade3 with exception of abnormal clinical laboratory values with no clinical significance and events which can be managed and controlled to Grade2 or less by maximal medical management within 7days, participant administered<70% of prescribed dose due to intolerable toxicity.

Secondary Outcome Measures

Measure:Cmax: Maximum Observed Plasma Concentration of H3B-6545
Time Frame:Cycle 1 Days 1 and 15: 0-24 hours (cycle length =28 days)
Safety Issue:
Description:
Measure:Tmax: Time of Maximum Observed Plasma Concentration of H3B-6545
Time Frame:Cycle 1 Days 1 and 15: 0-24 hours (cycle length =28 days)
Safety Issue:
Description:
Measure:AUC 0-t: Area Under the Concentration-time Curve From Zero (Pre-dose) to Time of Last Quantifiable Concentration of H3B-6545
Time Frame:Cycle 1 Days 1 and 15: 0-24 hours (cycle length =28 days)
Safety Issue:
Description:
Measure:Rac: Accumulation Ratio of H3B-6545
Time Frame:Cycle 1 Days 1 and 15: 0-24 hours (cycle length =28 days)
Safety Issue:
Description:
Measure:AUC 0-inf: Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of H3B-6545
Time Frame:Cycle 1 Days 1 and 15: 0-24 hours (cycle length =28 days)
Safety Issue:
Description:
Measure:T1/2: Terminal Half-life of H3B-6545
Time Frame:Cycle 1 Days 1 and 15: 0-24 hours (cycle length =28 days)
Safety Issue:
Description:
Measure:CL/F: Apparent Total Body Clearance of H3B-6545
Time Frame:Cycle 1 Days 1 and 15: 0-24 hours (cycle length =28 days)
Safety Issue:
Description:
Measure:Vz/F: Apparent Volume of Distribution at Terminal Phase of H3B-6545
Time Frame:Cycle 1 Days 1 and 15: 0-24 hours (cycle length =28 days)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Eisai Co., Ltd.

Trial Keywords

  • H3B-6545
  • ER-positive
  • HER2-negative

Last Updated

September 24, 2020