Clinical Trials /

Study Evaluating Abemaciclib + Aromatase Inhibitors in HR+, HER2- Advanced Breast Cancer Patients (HERMIONE-7)

NCT04227327

Description:

The HERMIONE-7 trial is a phase II, single-arm, open-label, multicenter study in HR+, HER2− advanced breast cancer patients who have received HD-FUL as first-line endocrine treatment for their metastatic disease. Patients will receive aromatase inhibitors plus Abemaciclib.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study Evaluating Abemaciclib + Aromatase Inhibitors in HR+, HER2- Advanced Breast Cancer Patients (HERMIONE-7)
  • Official Title: A Phase 2, Open Label, Multicenter, Single Arm Trial Evaluating the Activity and Safety of Abemaciclib + Aromatase Inhibitors (AIs) After 1st-line Treatment With High-Dose Fulvestrant in Hormone-Receptor-Positive (HR+), Human-Epidermal-Growth-factor-negative (HER2-) Advanced Breast Cancer Patients. The HERMIONE-7 Trial

Clinical Trial IDs

  • ORG STUDY ID: HERMIONE-7
  • NCT ID: NCT04227327

Conditions

  • Advanced Breast Cancer

Interventions

DrugSynonymsArms
AbemaciclibAbemaciclib + aromatase inhibitors
Aromatase InhibitorsAbemaciclib + aromatase inhibitors

Purpose

The HERMIONE-7 trial is a phase II, single-arm, open-label, multicenter study in HR+, HER2− advanced breast cancer patients who have received HD-FUL as first-line endocrine treatment for their metastatic disease. Patients will receive aromatase inhibitors plus Abemaciclib.

Detailed Description

      Hormone receptor positive tumors represent the most common form of breast cancer and account
      for most of the deaths from the disease. Endocrine therapy (ET) represents the main initial
      therapeutic strategy for these patients and has been associated with significant clinical
      benefits in the majority of them.

      Key-Topics for rationale:

        -  Fulvestrant, an Estrogen-Receptor (ER) antagonist with no known agonist effects,
           suppresses estrogen signaling by binding to and degrading the ER. Fulvestrant was
           approved as a monthly 250 mg dosing regimen based on TTP data demonstrating
           non-inferiority versus anastrozole in postmenopausal women whose advanced breast cancer
           had progressed during prior anti-estrogen therapy.

        -  The international CONFIRM trial compared Fulvestrant 500 mg (High-Dose Fulvestrant
           HD-FUL: Fulvestrant 500 mg every month with an additional 500 mg loading dose on Day 14
           of the first month) with the monthly 250 mg dose and demonstrated that HD-FUL mg was
           associated with improved progression-free survival (PFS) and overall survival (OS) in
           postmenopausal women with ER-positive (ER+) advanced breast cancer whose disease had
           recurred or progressed after prior endocrine therapy.

        -  The FALCON study evaluated the efficacy and safety of HD-FUL in comparison to
           anastrozole in HR+, HER2- recurrent or metastatic breast cancer (MBC) patients. Median
           duration of PFS with HD-FUL was 16·6 months (95% CI 13·83-20·99) in the whole population
           and 22.3 months (95% CI 16·62-32·79) in the non-visceral one. Grade 3 or worse adverse
           events were reported by 51 (22%) of 228 patients receiving HD-FUL.

        -  Palbociclib, Abemaciclib and Ribociclib + Fulvestrant are superior to Fulvestrant alone
           in terms of PFS (PALOMA-3: 9.5 vs 4.6 months; MONARCH-2: 16.4 vs 9.3; MONALEESA-3: 20.5
           vs 12.8) in patients who have received prior endocrine therapy for advanced disease or
           have relapsed during or within 1 month from adjuvant therapy.

        -  A descriptive study analyzed European treatment patterns for HR-positive MBC patients in
           real-world clinical practice in the years 2004 - 2013 showed that Fulvestrant was the
           initial therapy for advanced disease in 0.8 - 2.6% of the patients. However, the ongoing
           real-world GIM-13 AMBRA study showed that in Italy this percentage has grown up to 30%.

      At the moment, no data are available regarding the activity of CDK 4/6 inhibitors in patients
      treated with HD-FUL as 1st-line therapy, nor are there ongoing trials in this setting.

      The aim of this study is to describe the activity of Abemaciclib + aromatase inhibitors (AIs
      - letrozole or anastrozole) in HD-FUL pre-treated MBC patients in terms of Clinical Benefit
      Rate (CBR).

      This is a phase II, single-arm, open-label, multicenter study in HR+, HER2− advanced breast
      cancer patients who have received HD-FUL as first-line endocrine treatment for their
      metastatic disease. Patients will receive aromatase inhibitors plus Abemaciclib.. Abemaciclib
      will be administered orally at 150 mg twice daily until evidence of disease recurrence or
      other discontinuation criteria are met, whichever occurs first, together with AIs, as per
      specific product instructions. The Simon's optimal two-stage design will be used for the
      conduction of the trial.
    

Trial Arms

NameTypeDescriptionInterventions
Abemaciclib + aromatase inhibitorsExperimentalAbemaciclib will be administered at 150 mg twice daily orally + Letrozole 2,5 mg daily or Anastrozole 1 mg daily
  • Abemaciclib
  • Aromatase Inhibitors

Eligibility Criteria

        Inclusion Criteria:

          1. Female ≥ 18 years of age regardless of menopausal status, who have relapsed while on
             prior first-line therapy with HD-FUL

          2. Patients with advanced (loco-regionally recurrent, or metastatic) breast cancer not
             amenable to curative therapy.

          3. Patient has a histological and/or cytological confirmed diagnosis of estrogen-receptor
             positive and/or progesterone receptor positive breast cancer by local laboratory.

          4. Patient has HER2-negative breast cancer defined as a negative in situ hybridization
             test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization
             (FISH, CISH, or SISH) test is required by local laboratory testing.

          5. WHO performance status of 0-2

          6. Measurable disease (according to Response Evaluation Criteria in Solid Tumors
             [RECIST], version 1.1) or at least one lytic bone lesion

          7. The patient is able to swallow oral medications.

          8. The patient has adequate organ function

          9. Patient has signed ICF (ICF) obtained before any trial-related activities Patients
             must be able to communicate with the investigator and comply with the requirements of
             the study procedures.

        Exclusion Criteria:

          1. Patient has a known hypersensitivity to any of the excipients of Abemaciclib or
             letrozole/anastrozole

          2. Patient who received any CDK4/6 inhibitor

          3. Patient who received > 1 prior systemic hormonal therapy for advanced breast cancer;
             the only admitted previous therapy as 1st-line treatment is HD FUL. Note: Patients who
             received ≤ 28 days of letrozole or anastrozole for advanced disease prior to inclusion
             in this trial are eligible.

          4. Patient who has not had resolution of all acute toxic effects of prior anti-cancer
             therapy to NCI CTCAE version 4.03 Grade ≤ 1 (except alopecia or other toxicities not
             considered a safety risk for the patient at investigator's discretion)

          5. Patient who has received extended-field radiotherapy ≤ 4 weeks or limited field
             radiotherapy for palliation ≤ 2 weeks prior to start of treatment, and who has not
             recovered to grade 1 or better from related side effects of such therapy (with the
             exception of alopecia or other toxicities not considered a safety risk for the patient
             at the investigator's discretion).

          6. Patients from whom ≥ 25% (Ellis RE 1961) of the bone marrow has been previously
             irradiated are also excluded.

          7. Patient has a concurrent malignancy or malignancy within 3 years prior to starting
             study drug, with the exception of treated, basal or squamous cell carcinoma, non
             melanomatous skin cancer or curatively resected cervical cancer.

          8. Patient with central nervous system (CNS) metastases unless they meet ALL of the
             following criteria:

               1. At least 4 weeks from prior therapy for CNS disease completion (including
                  radiation and/or surgery) to starting the study treatment

               2. Clinically stable CNS lesions at the time of study treatment initiation and not
                  receiving steroids and/or enzyme-inducing anti-epileptic medications for the
                  management of brain metastases for at least 2 weeks

          9. Patient has impairment of gastrointestinal (GI) function or GI disease that may
             significantly alter the absorption of the study drugs (e.g., uncontrolled ulcerative
             diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small
             bowel resection, or preexisting Crohn's disease or ulcerative colitis, or a
             preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea)

         10. Patient has a known history of HIV infection (testing not mandatory)

         11. The patient has serious preexisting medical condition(s) that, in the judgment of the
             investigator, would preclude participation in this study (such as severe renal
             impairment, [for example, estimated creatinine clearance <30 mL/min], interstitial
             lung disease, sever dyspnea at rest or requiring oxygen therapy

         12. The patient has a personal history of any of the following conditions: syncope of
             cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but
             not limited to, ventricular tachycardia and ventricular fibrillation), or sudden
             cardiac arrest. Exception: patients with controlled atrial fibrillation for >30 days
             prior to randomization are eligible. Any patient with a history of VTE (for example,
             DVT of the leg or arm and/or PE) will be excluded.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Clinical benefit rate (CBR) in HD-FUL pre-treated MBC patients treated with Abemaciclib + aromatase inhibitors (letrozole or anastrozole)
Time Frame:At 6 months from treatment initiation
Safety Issue:
Description:CBR is defined as the proportion of patients in Complete Response (CR), Partial Response (PR) or with Stable Disease (SD) >= 24 weeks (as defined by RECIST 1.1 Criteria) evaluated at 6 months from treatment initiation.

Secondary Outcome Measures

Measure:Time To Progression (TTP)
Time Frame:Through study completion, an average of 42 months
Safety Issue:
Description:TTP is defined as the time from date of start of treatment to the date of event, i.e. the first documented progression or death due to underlying cancer
Measure:Overall Response Rate (ORR)
Time Frame:Through study completion, an average of 42 months
Safety Issue:
Description:ORR is defined as the proportion of patients with best overall response of CR or PR) according to RECIST 1.1.
Measure:Duration of Overall Response (DoOR)
Time Frame:Through study completion, an average of 42 months
Safety Issue:
Description:DoOR is defined as the time of initial response until documented tumor progression
Measure:Duration of Clinical Benefit (DoCB)
Time Frame:Through study completion, an average of 42 months
Safety Issue:
Description:DoCB is defined as the time of initial CB until documented tumor progression
Measure:To assess the safety profile of Abemaciclib in association with aromatase inhibitors (letrozole or anastrozole)
Time Frame:Through study completion, an average of 42 months
Safety Issue:
Description:The Medical Dictionary for Regulatory Activities (MedDRA) Version 19.0 (or higher) will be used when reporting AEs by MedDRA terms. The MedDRA Lower Level Term will be used in the treatment-emergent computation. Treatment-emergent adverse events will be summarized by System Organ Class (SOC) and by decreasing frequency of Preferred Term within SOC.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Milano Bicocca

Trial Keywords

  • abemaciclib
  • Hormone-Receptor-Positive (HR+)
  • Human-Epidermal-Growth-factor-negative (HER2-)

Last Updated

January 14, 2020