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.
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
Interventions
Drug | Synonyms | Arms |
---|
Abemaciclib | | Abemaciclib + aromatase inhibitors |
Aromatase Inhibitors | | Abemaciclib + 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
Name | Type | Description | Interventions |
---|
Abemaciclib + aromatase inhibitors | Experimental | Abemaciclib 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: | Recruiting |
Lead Sponsor: | University of Milano Bicocca |
Trial Keywords
- abemaciclib
- Hormone-Receptor-Positive (HR+)
- Human-Epidermal-Growth-factor-negative (HER2-)
Last Updated
July 13, 2021