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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

NCT04572295

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT04572295

Trial Eligibility

Document

Title

  • Brief Title: 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
  • 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

Clinical Trial IDs

  • ORG STUDY ID: E7090-J081-102
  • NCT ID: NCT04572295

Conditions

  • Breast Neoplasms

Interventions

DrugSynonymsArms
E7090Part 1 Dose Escalation: E7090 + Fulvestrant or Exemestane
FulvestrantPart 1 Dose Escalation: E7090 + Fulvestrant or Exemestane
ExemestanePart 1 Dose Escalation: E7090 + Fulvestrant or Exemestane

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Part 1 Dose Escalation: E7090 + Fulvestrant or ExemestaneExperimentalParticipants 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.
  • E7090
  • Fulvestrant
  • Exemestane
Part 2 Monotherapy: E7090ExperimentalParticipants will receive E7090 tablets, orally, once daily in 28 days cycle. Each cycle length =28 days.
  • E7090
Part 3 Dose Expansion: E7090 + Fulvestrant or ExemestaneExperimentalParticipants will receive E7090 tablets, orally, once daily along with fulvestrant 500 mg, intramuscular injection on Days 1 and 15, or along with exemestane 25 mg, tablet, once daily in 28 days cycle. Each cycle length =28 days. The dose of E7090 for Part 3 in combination with fulvestrant or exemestane will be determined based on the safety, tolerability, pharmacokinetic (PK), and biomarker data obtained from Part 1.
  • E7090
  • Fulvestrant
  • Exemestane

Eligibility 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 female (with medical menopause by treatment
             with a luteinizing hormone-releasing hormone (LHRH) agonist).

          4. Participants with pathologically confirmed diagnosis of recurrent/metastatic, ER+,
             HER2 negative breast cancer.

          5. Participants who have adequate bone marrow and organ function.

          6. Participants with Performance Status (PS) score of 0-1 established by Eastern
             Cooperative Oncology Group (ECOG).

          7. Participants with at least one accessible lesion for biopsy and who agree to undergo a
             biopsy of accessible lesion.

          8. Participants who agree to provide archival or fresh tumor tissue.

          9. Part 2 and 3 only: Participants with fibroblast growth factor receptor (FGFR) positive
             tumor.

        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. Participant with inflammatory breast cancer.

          4. Participant with bilateral breast cancer.

          5. Participant who have history of active malignancy within the past 24 months.

          6. Participants with clinically significant cardiovascular impairment.

          7. Presence of a progressive central nervous system (CNS) disease, including degenerative
             CNS diseases and progressive tumors.

          8. Concomitant active infection requiring systemic treatment.

          9. 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).

         10. 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).

         11. Participants who received prior treatment with an FGFR inhibitor.

         12. Females who are pregnant or breastfeeding.
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1: Recommended Dose (RD) of E7090 in Combination With Other Anticancer Agents
Time Frame:Up to Cycle 1 (each cycle length = 28 days)
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure:Part 1: Plasma Concentration of Fulvestrant
Time Frame:Cycles 2 and 3 Day 1: pre-dose (each cycle length = 28 days)
Safety Issue:
Description:
Measure:Objective Response Rate (ORR)
Time Frame:Baseline up to 42 months
Safety Issue:
Description: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.
Measure:Disease Control Rate (DCR)
Time Frame:Baseline up to 42 months
Safety Issue:
Description: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.
Measure:Clinical Benefit Response (CBR)
Time Frame:Baseline up to 42 months
Safety Issue:
Description: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.
Measure:Progression-free Survival (PFS)
Time Frame:Baseline up to 42 months
Safety Issue:
Description: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.
Measure:Overall Survival (OS)
Time Frame:Baseline up to 42 months
Safety Issue:
Description:OS is defined as the time from the date of first dose to the date of death from any cause.
Measure:Time to Response (TTR)
Time Frame:Baseline up to 42 months
Safety Issue:
Description: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.
Measure:Duration of Response (DOR)
Time Frame:Baseline up to 42 months
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Eisai Co., Ltd.

Trial Keywords

  • E7090
  • Fulvestrant
  • Exemestane
  • Receptors, Fibroblast Growth Factor

Last Updated

December 10, 2020