Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of H3B-6545 in Combination With Palbociclib in Women With Advanced or Metastatic Estrogen Receptor-Positive Human Epidermal Growth Factor Receptor-2 (HER2)-Negative Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04288089
Recruitment Status : Active, not recruiting
First Posted : February 27, 2020
Last Update Posted : May 31, 2022
Sponsor:
Collaborator:
Eisai Inc.
Information provided by (Responsible Party):
Eisai Inc. ( H3 Biomedicine Inc. )

Brief Summary:
The primary objective of this study is to evaluate the safety and tolerability of H3B-6545 and palbociclib when administered in combination in order to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of this combination in women with advanced or metastatic estrogen receptor-positive (ER+) HER2- breast cancer.

Condition or disease Intervention/treatment Phase
Receptors, Estrogen Genes, Erbb-2 Breast Neoplasms Drug: Palbociclib (75, 100, 125 milligram [mg]) Drug: H3B-6545 (150, 300, 450 mg) Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Multicenter Phase 1b Study of H3B-6545 in Combination With Palbociclib in Women With Advanced or Metastatic Estrogen Receptor-Positive HER2-Negative Breast Cancer
Actual Study Start Date : April 1, 2020
Estimated Primary Completion Date : September 30, 2022
Estimated Study Completion Date : March 31, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Palbociclib

Arm Intervention/treatment
Experimental: Palbociclib + H3B-6545 (Dose Escalation and Dose Expansion)
Participants will receive Palbociclib 75, 100, 125 milligram (mg) capsules or tablets, orally, once daily from Days 1 to 21 followed by 7 days off treatment in 28-day cycles along with H3B-6545 150, 300, 450 mg capsules or tablets, orally, once daily from Days 1 to 28 in 28-day cycles in dose escalation part. Based on MTD or RP2D determined for H3B-6545 in combination with palbociclib in dose escalation part, participants will continue to receive study treatment in dose expansion part until PD, development of unacceptable toxicity, or withdrawal of consent (up to 24 months).
Drug: Palbociclib (75, 100, 125 milligram [mg])
Palbociclib orally, once daily (QD).

Drug: H3B-6545 (150, 300, 450 mg)
H3B-6545 orally, QD.




Primary Outcome Measures :
  1. Dose Escalation Part: MTD and/or RP2D of Palbociclib and H3B-6545 [ Time Frame: From Cycle 1 Day 9 up to Cycle 2 Day 8 (Each cycle length is equal to [=] 28 days) ]

Secondary Outcome Measures :
  1. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: From first dose up to 28 days after the last dose of study drug (up to Month 24) ]
  2. AUC(0-t): Area Under the Plasma Concentration-time Curve from Time 0 to the Last Measurable Point for Palbociclib and H3B-6545 [ Time Frame: Dose Escalation Part: Cycle 1 Days 8, 21 and 28: 0-24 hours postdose; Dose Expansion Part: Cycle 1 Day 21: 0-24 hours postdose (Each Cycle length=28 days) ]
  3. Cmax: Maximum Observed Plasma Concentration for Palbociclib and H3B-6545 [ Time Frame: Dose Escalation Part: Cycle 1 Days 8, 21 and 28: 0-24 hours postdose; Dose Expansion Part: Cycle 1 Day 21: 0-24 hours postdose (Each Cycle length=28 days) ]
  4. Tmax: Time to Reach the Cmax for Palbociclib and H3B-6545 [ Time Frame: Dose Escalation Part: Cycle 1 Days 8, 21 and 28: 0-24 hours postdose; Dose Expansion Part: Cycle 1 Day 21: 0-24 hours postdose (Each Cycle length=28 days) ]
  5. C24: Plasma Concentration at 24 hour Post-dose for Palbociclib and H3B-6545 [ Time Frame: Dose Escalation Part: Cycle 1 Days 8, 21 and 28: 0-24 hours postdose; Dose Expansion Part: Cycle 1 Day 21: 0-24 hours postdose (Each Cycle length=28 days) ]
  6. Ratio of Pharmacokinetic (PK) Cmax Parameter Estimates Between Day 21 (Palbociclib) and Day 8 (Palbociclib) [ Time Frame: Dose Escalation Part: Cycle 1 Days 8 and 21: 0-24 hours postdose; Dose Expansion Part: Cycle 1 Day 21: 0-24 hours postdose (Each Cycle length=28 days) ]
    Ratio of palbociclib Cmax Day 21/Day 8, is the ratio of palbociclib exposure on Day 21 and palbociclib exposure on Day 8.

  7. Ratio of PK AUC24 Parameter Estimates Between Day 21 (Palbociclib) and Day 8 (Palbociclib) [ Time Frame: Dose Escalation Part: Cycle 1 Days 8 and 21: 0-24 hours postdose; Dose Expansion Part: Cycle 1 Day 21: 0-24 hours postdose (Each Cycle length=28 days) ]
    Ratio of palbociclib AUC24 Day 21/Day 8, is the ratio of palbociclib exposure on Day 21 and palbociclib exposure on Day 8.

  8. Ratio of PK C24 Parameter Estimates Between Day 21 (Palbociclib) and Day 8 (Palbociclib) [ Time Frame: Dose Escalation Part: Cycle 1 Days 8 and 21: 0-24 hours postdose; Dose Expansion Part: Cycle 1 Day 21: 0-24 hours postdose (Each Cycle length=28 days) ]
    Ratio of palbociclib C24 Day 21/Day 8, is the ratio of palbociclib exposure on Day 21 and palbociclib exposure on Day 8.

  9. Ratio of PK Cmax Parameter Estimates Between Day 21 (H3B-6545) and Day 28 (H3B-6545) [ Time Frame: Dose Escalation Part: Cycle 1 Days 21 and 28: 0-24 hours postdose; Dose Expansion Part: Cycle 1 Day 21: 0-24 hours postdose (Each Cycle length=28 days) ]
    Ratio of palbociclib Cmax Day 21/Day 28, is the ratio of H3B-6545 exposure on Day 21 and H3B-6545 exposure on Day 28.

  10. Ratio of PK AUC24 Parameter Estimates Between Day 21 (H3B-6545) and Day 28 (H3B-6545) [ Time Frame: Dose Escalation Part: Cycle 1 Days 21 and 28: 0-24 hours postdose; Dose Expansion Part: Cycle 1 Day 21: 0-24 hours postdose (Each Cycle length=28 days) ]
    Ratio of H3B-6545 AUC24 Day 21/Day 28, is the ratio of H3B-6545 exposure on Day 21 and H3B-6545 exposure on Day 28.

  11. Ratio of PK C24 Parameter Estimates Between Day 21 (H3B-6545) and Day 28 (H3B-6545) [ Time Frame: Dose Escalation Part: Cycle 1 Days 21 and 28: 0-24 hours postdose; Dose Expansion Part: Cycle 1 Day 21: 0-24 hours postdose (Each Cycle length=28 days) ]
    Ratio of H3B-6545 C24 Day 21/Day 28, is the ratio of H3B-6545 exposure on Day 21 and H3B-6545 exposure on Day 28.

  12. Objective Response Rate (ORR) [ Time Frame: From first dose of study drug up to Month 24 ]
    ORR is defined as the percentage of participants achieving a best overall response (BOR) of confirmed partial response (PR) or complete response (CR). The ORR will be assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

  13. Duration of Response (DoR) [ Time Frame: From the date of first documented CR/PR until the PD or death, whichever occurs first (up to Month 24) ]
    DoR is defined as the time from the date of the first documented CR/PR until the first documentation of disease progression (PD) or death, whichever comes first. The DoR will be assessed according to RECIST version 1.1.

  14. Clinical Benefit Rate (CBR) [ Time Frame: From the first dose of study drug until disease progression or death, whichever occurs first (up to Month 24) ]
    CBR is defined as the percentage of participants with BOR of PR, CR, or durable stable disease (SD) (duration of SD greater than or equal to 23 weeks). Duration of SD is defined as the time from the date of first dose to the date of the first documentation of disease progression or death, whichever occurs first. It will be calculated for participants whose BOR is SD. The CBR will be assessed according to RECIST version 1.1.

  15. Progression-free Survival (PFS) [ Time Frame: From first dose of study drug until first documentation of PD or death, whichever occurs first (up to Month 24) ]
    PFS is defined as the time from the first dose date to the date of the first documentation of PD or death (whichever occurs first).

  16. Overall Survival (OS) [ Time Frame: From the date of first dose to the date of death from any cause (up to Month 24) ]
    OS is defined as the time from first dose date to the date of death from any cause.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. ER+ HER2- locally advanced, recurrent, or metastatic breast cancer, as per local laboratory
  2. Prior therapy in the advanced/metastatic setting
  3. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  4. Has adequate bone marrow and organ function

Exclusion Criteria:

  1. Uncontrolled significant active infections
  2. Major surgery or other locoregional treatment within 4 weeks before the 1st dose of study drug
  3. Inability to take oral medication or presence of malabsorption
  4. Active cardiac disease or a history of cardiac dysfunction
  5. Evidence of ongoing Alcohol or Drug Abuse

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04288089


Locations
Layout table for location information
United States, Florida
Florida Cancer Specialists South - SCRI - PPDS
Sarasota, Florida, United States, 34232
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Missouri
Saint Luke's Cancer Institute
Kansas City, Missouri, United States, 64111
United States, Nevada
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, United States, 89169
United States, Tennessee
Tennessee Oncology, PLLC - SCRI - PPDS
Nashville, Tennessee, United States, 37203
United Kingdom
Royal Marsden NHS Foundation Trust
London, United Kingdom
Sarah Cannon Research Institute UK - SCRI
London, United Kingdom
Royal Marsden NHS Foundation Trust
Sutton, United Kingdom
Sponsors and Collaborators
H3 Biomedicine Inc.
Eisai Inc.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: H3 Biomedicine Inc.
ClinicalTrials.gov Identifier: NCT04288089    
Other Study ID Numbers: H3B-6545-G000-102
2019-004622-17 ( EudraCT Number )
First Posted: February 27, 2020    Key Record Dates
Last Update Posted: May 31, 2022
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eisai Inc. ( H3 Biomedicine Inc. ):
H3B-6545
Palbociclib
Metastatic Estrogen Receptor-Positive
HER2-Negative Breast Cancer
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Palbociclib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action