We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of E7090 as Monotherapy and in Combination With Other Anticancer Agents in Participants With Estrogen Receptor Positive (ER+) and Human Epidermal Growth Receptor 2 Negative (HER2-) Recurrent/Metastatic 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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04572295
Recruitment Status : Recruiting
First Posted : October 1, 2020
Last Update Posted : August 23, 2022
Sponsor:
Information provided by (Responsible Party):
Eisai Inc. ( Eisai Co., Ltd. )

Brief Summary:
The primary purpose of this study is to evaluate the tolerability and safety of E7090 as monotherapy and in combination with other anticancer agents in participants with ER+, HER2- recurrent/metastatic breast cancer and also to determine the recommended dose (RD) of E7090 in combination with other anticancer agents for subsequent phase studies.

Condition or disease Intervention/treatment Phase
Breast Neoplasms Drug: E7090 Drug: Fulvestrant Drug: Exemestane Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label Phase 1b Study of E7090 Monotherapy and in Combination With Other Anticancer Agents in Subjects With ER+, HER2- Recurrent/Metastatic Breast Cancer
Actual Study Start Date : October 9, 2020
Estimated Primary Completion Date : April 30, 2024
Estimated Study Completion Date : April 30, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Part 1 Dose Escalation: E7090 + Fulvestrant or Exemestane
Participants will receive E7090 tablets, orally, once daily along with fulvestrant 500 milligram (mg), intramuscular injection on Days 1 and 15 of Cycle 1 and each Day 1 of cycle 2 or later, or along with exemestane 25 mg tablet, orally, once daily in 28 days cycle. Each cycle length equals to (=) 28 days.
Drug: E7090
E7090 oral tablet.

Drug: Fulvestrant
Fulvestrant intramuscular injection.

Drug: Exemestane
Exemestane oral tablet.

Experimental: Part 2 Monotherapy: E7090
Participants will receive E7090 tablets, orally, once daily in 28 days cycle. Each cycle length =28 days.
Drug: E7090
E7090 oral tablet.

Experimental: Part 3 Dose Expansion: E7090 + Fulvestrant

Participants will receive E7090 tablets, orally, once daily along with fulvestrant 500 mg, intramuscular injection on Days 1 and 15 of Cycle 1 and each Day 1 of cycle 2 or later. Each cycle length =28 days.

The dose of E7090 for Part 3 in combination with fulvestrant will be determined based on the safety, tolerability, pharmacokinetic (PK), and biomarker data obtained from Part 1.

Drug: E7090
E7090 oral tablet.

Drug: Fulvestrant
Fulvestrant intramuscular injection.




Primary Outcome Measures :
  1. Part 1: Recommended Dose (RD) of E7090 in Combination With Other Anticancer Agents [ Time Frame: Up to Cycle 1 (each cycle length = 28 days) ]
  2. Part 1: Number of Participants With Dose-limiting Toxicities (DLTs) [ Time Frame: Up to Cycle 1 (each cycle length = 28 days) ]
    DLTs will be assessed based on combination regimen-related adverse events (AEs) occurred during Cycle 1 of Part 1 and the severity of AEs will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

  3. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to 30 days after last administration of study drug (approximately up to 42 months) ]
    Safety assessments will consist of monitoring and recording all AEs and SAEs; regular measurement of vital signs and ECG; and regular monitoring of clinical laboratory parameters, body weight and bone density.


Secondary Outcome Measures :
  1. Cmax: Maximum Observed Plasma Concentration of E7090, its Metabolite (M2) and Exemestane [ Time Frame: For E7090 and its metabolite (M2)- Parts 1 and 2 Cycle 1 Day 1: 0-24 hours post-dose; For exemestane- Part 1 Cycle 1 Day 1: 0-24 hours post-dose (each cycle length = 28 days) ]
  2. AUC: Area Under the Plasma Concentration-time Curve of E7090, its Metabolite (M2) and Exemestane [ Time Frame: For E7090 and its metabolite (M2)- Parts 1 and 2 Cycle 1 Day 1: 0-24 hours post-dose; For exemestane- Part 1 Cycle 1 Day 1: 0-24 hours post-dose (each cycle length = 28 days) ]
  3. Part 1: Plasma Concentration of Fulvestrant [ Time Frame: Cycles 2 and 3 Day 1: pre-dose (each cycle length = 28 days) ]
  4. Objective Response Rate (ORR) [ Time Frame: Baseline up to 42 months ]
    The ORR will be assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. ORR is defined as a percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR). CR: disappearance of all lesions. PR: For PR, longest diameter will be used for non-lymph target lesions but short axis is measured for lymph lesions. PR: greater than or equal to (>=) 30 percent (%) decrease in sum of diameters of target lesions taking as reference baseline, associated to non-progressive disease (non-PD) response for non-target (NT) lesions.

  5. Disease Control Rate (DCR) [ Time Frame: Baseline up to 42 months ]
    DCR will be assessed according to RECIST version 1.1. DCR is defined as a percentage of participants with BOR of CR, PR or stable disease (SD). The BOR of SD has to be observed >=7 weeks from the date of first study dose. CR: disappearance of all lesions. PR: For PR, longest diameter will be used for non-lymph target lesions but short axis is measured for lymph lesions. PR: >=30% decrease in sum of diameters of target lesions taking as reference baseline, associated to non-PD response for NT lesions.

  6. Clinical Benefit Response (CBR) [ Time Frame: Baseline up to 42 months ]
    CBR will be assessed according to RECIST version 1.1. CBR is defined as a percentage of participants with BOR of CR, PR or durable SD (dSD) (duration of SD >=23 weeks). CR: disappearance of all lesions. PR: For PR, longest diameter will be used for non-lymph target lesions but short axis is measured for lymph lesions. PR: >=30% decrease in sum of diameters of target lesions taking as reference baseline, associated to non-PD response for NT lesions.

  7. Progression-free Survival (PFS) [ Time Frame: Baseline up to 42 months ]
    PFS will be assessed according to RECIST version 1.1. PFS is defined as the time from the date of first dose to the date of first documentation of disease progression or date of death from any cause, whichever occurs first.

  8. Overall Survival (OS) [ Time Frame: Baseline up to 42 months ]
    OS is defined as the time from the date of first dose to the date of death from any cause.

  9. Time to Response (TTR) [ Time Frame: Baseline up to 42 months ]
    TTR will be assessed according to RECIST version 1.1. TTR is defined as the time from the date of first study dose to the date of first documentation of CR or PR. CR: disappearance of all lesions. PR: For PR, longest diameter will be used for non-lymph target lesions but short axis is measured for lymph lesions. PR: >=30% decrease in sum of diameters of target lesions taking as reference baseline, associated to non-PD response for NT lesions.

  10. Duration of Response (DOR) [ Time Frame: Baseline up to 42 months ]
    DOR will be assessed according to RECIST version 1.1. DOR is defined as the time from the date of first documentation of CR or PR to the date of first documentation of disease progression or date of death from any cause, whichever occurs first. CR: disappearance of all lesions. PR: For PR, longest diameter will be used for non-lymph target lesions but short axis is measured for lymph lesions. PR: >=30% decrease in sum of diameters of target lesions taking as reference baseline, associated to non-PD response for NT lesions.



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:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Provide written informed consent.
  2. Female participants who are age >=20 years at the time of informed consent.
  3. Post-menopausal or pre/peri-menopausal concurrently given a luteinizing hormone-releasing hormone (LHRH) agonist before the start of trial therapy and is planned to continue LHRH agonist during the study.
  4. Participants with pathologically confirmed diagnosis of recurrent/metastatic, ER+, HER2 negative breast cancer.
  5. Participants who received prior CDK4/6 inhibitor treatment.
  6. Participants with Performance Status (PS) score of 0-1 established by Eastern Cooperative Oncology Group (ECOG).
  7. Part 1 and Part 2: Participants with at least one accessible lesion prior to study treatment (if archived tissues collected after CDK4/6 inhibitor treatment is not available) and on Cycle 3 Day 1. Part 3 participants must agree to undergo a biopsy at screening if no archival tissue is available (tissue collection must be after CDK4/6 inhibitor treatment and prior to study treatment). Collection of fresh tumor tissue on Cycle 3 Day 1 is not mandatory.
  8. Participants who agree to provide archival or fresh tumor tissue collected after CDK4/6 inhibitor treatment.
  9. Part 2 only: Participants with fibroblast growth factor receptor (FGFR) positive tumor collected after CDK4/6 inhibitor treatment at the central laboratory.

Exclusion criteria:

  1. Participants with brain or subdural metastases, 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.
  2. Participant who have received more than 2 regimen of chemotherapy in the metastatic setting.
  3. For Part 3, participant who have received chemotherapy in the metastatic setting.
  4. Participant with inflammatory breast cancer.
  5. Participant with bilateral breast cancer.
  6. Participant who have history of active malignancy within the past 24 months prior to the first dose of study drugs.
  7. Participants with clinically significant cardiovascular impairment.
  8. Presence of a progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors.
  9. Concomitant active infection requiring systemic treatment.
  10. Participants who test positive for human immunodeficiency virus (HIV antibody), or positive for hepatitis B surface (HBs antigen) or hepatitis C (HCV antibody and RNA).
  11. Participants with following ocular disorders:

    1. Current evidence of Grade 2 or higher corneal disorder
    2. Current evidence of active retinopathy (example. age-related macular degeneration, central serous chorioretinal disease, retinal tear)
  12. Participants who received prior treatment with an FGFR inhibitor.
  13. Females who are pregnant or breastfeeding.
  14. Part 1 only: Participants with T-score less than (<) -2.5 by dual-energy X-ray absorptiometry (DXA) scan.
  15. Part 3 only: Participants who received prior treatment with Fulvestrant except for in combination with CDK4/6 inhibitor.

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): NCT04572295


Contacts
Layout table for location contacts
Contact: Eisai Inquiry Service eisai-chiken_hotline@hhc.eisai.co.jp

Locations
Layout table for location information
Japan
Eisai Trial Site 11 Not yet recruiting
Nagoya, Aichi, Japan
Eisai Trial Site 6 Recruiting
Kashiwa, Chiba, Japan
Eisai Trial Site 9 Recruiting
Matsuyama, Ehime, Japan
Eisai Trial Site 5 Recruiting
Yokohama, Kanagawa, Japan
Eisai Trial Site 4 Recruiting
Sendai, Miyagi, Japan
Eisai Trial Site 7 Recruiting
Chuo-ku, Osaka, Japan
Eisai Trial Site 10 Recruiting
Kitaadachi-gun, Saitama, Japan
Eisai Trial Site 3 Recruiting
Chuo-ku, Tokyo, Japan
Eisai Trial Site 1 Recruiting
Koto-ku, Tokyo, Japan
Eisai Trial Site 2 Recruiting
Shinagawa-ku, Tokyo, Japan
Eisai Trial Site 8 Recruiting
Shinjuku-ku, Tokyo, Japan
Sponsors and Collaborators
Eisai Co., Ltd.
Layout table for additonal information
Responsible Party: Eisai Co., Ltd.
ClinicalTrials.gov Identifier: NCT04572295    
Other Study ID Numbers: E7090-J081-102
First Posted: October 1, 2020    Key Record Dates
Last Update Posted: August 23, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Supporting Information: 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: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eisai Inc. ( Eisai Co., Ltd. ):
E7090
Fulvestrant
Exemestane
Receptors, Fibroblast Growth Factor
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Fulvestrant
Exemestane
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action