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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

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ClinicalTrials.gov Identifier: NCT04288089
Recruitment Status : Recruiting
First Posted : February 27, 2020
Last Update Posted : July 16, 2021
Sponsor:
Collaborator:
Eisai Inc.
Information provided by (Responsible Party):
Eisai Inc. ( H3 Biomedicine Inc. )

Tracking Information
First Submitted Date  ICMJE February 26, 2020
First Posted Date  ICMJE February 27, 2020
Last Update Posted Date July 16, 2021
Actual Study Start Date  ICMJE April 1, 2020
Estimated Primary Completion Date September 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 26, 2020)
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) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 26, 2020)
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • Ratio of PK Cmax Parameter Estimates Between Day 21 (Palbociclib) and Day 8 (Palbociclib) [ 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) ]
    Ratio of palbociclib Cmax Day 21/Day 8, is the ratio of palbociclib exposure on Day 21 and palbociclib exposure on Day 8.
  • Ratio of PK AUC24 Parameter Estimates Between Day 21 (Palbociclib) and Day 8 (Palbociclib) [ 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) ]
    Ratio of palbociclib AUC24 Day 21/Day 8, is the ratio of palbociclib exposure on Day 21 and palbociclib exposure on Day 8.
  • Ratio of PK C24 Parameter Estimates Between Day 21 (Palbociclib) and Day 8 (Palbociclib) [ 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) ]
    Ratio of palbociclib C24 Day 21/Day 8, is the ratio of palbociclib exposure on Day 21 and palbociclib exposure on Day 8.
  • Ratio of PK Cmax Parameter Estimates Between Day 21 (H3B-6545) and Day 28 (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) ]
    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.
  • Ratio of PK AUC24 Parameter Estimates Between Day 21 (H3B-6545) and Day 28 (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) ]
    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.
  • Ratio of PK C24 Parameter Estimates Between Day 21 (H3B-6545) and Day 28 (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) ]
    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.
  • 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 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.
  • 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.
  • Disease Control Rate (DCR) [ Time Frame: From first dose of study drug up to Month 24 ]
    DCR is defined as the percentage of participants achieving a best response of CR, PR, or stable disease (SD). The DCR will be assessed according to RECIST v1.1.
  • 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).
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Receptors, Estrogen
  • Genes, Erbb-2
  • Breast Neoplasms
Intervention  ICMJE
  • Drug: Palbociclib (75, 100, 125 milligram [mg])
    Palbociclib orally.
  • Drug: H3B-6545 (300, 450 mg)
    H3B-6545 orally.
Study Arms  ICMJE Experimental: Palbociclib + H3B-6545 (Escalation and Expansion)
Interventions:
  • Drug: Palbociclib (75, 100, 125 milligram [mg])
  • Drug: H3B-6545 (300, 450 mg)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 26, 2020)
36
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 31, 2024
Estimated Primary Completion Date September 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Eisai Medical Information 1-888-274-2378 esi_oncmedinfo@eisai.com
Listed Location Countries  ICMJE United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04288089
Other Study ID Numbers  ICMJE H3B-6545-G000-102
2019-004622-17 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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/.
Responsible Party Eisai Inc. ( H3 Biomedicine Inc. )
Study Sponsor  ICMJE H3 Biomedicine Inc.
Collaborators  ICMJE Eisai Inc.
Investigators  ICMJE Not Provided
PRS Account Eisai Inc.
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP