Study Evaluating Abemaciclib + Aromatase Inhibitors in HR+, HER2- Advanced Breast Cancer Patients (HERMIONE-7) (HERMIONE-7)
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|ClinicalTrials.gov Identifier: NCT04227327|
Recruitment Status : Recruiting
First Posted : January 13, 2020
Last Update Posted : April 8, 2021
|Condition or disease||Intervention/treatment||Phase|
|Advanced Breast Cancer||Drug: Abemaciclib Drug: Aromatase Inhibitors||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||121 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||January 7, 2020|
|Estimated Primary Completion Date :||July 2023|
|Estimated Study Completion Date :||December 2023|
Experimental: Abemaciclib + aromatase inhibitors
Abemaciclib will be administered at 150 mg twice daily orally + Letrozole 2,5 mg daily or Anastrozole 1 mg daily
Abemaciclib will be administered orally at 150 mg twice daily
Drug: Aromatase Inhibitors
Letrozole 2,5 mg daily or Anastrozole 1 mg daily
- 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 ]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.
- Time To Progression (TTP) [ Time Frame: Through study completion, an average of 42 months ]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
- Overall Response Rate (ORR) [ Time Frame: Through study completion, an average of 42 months ]ORR is defined as the proportion of patients with best overall response of CR or PR) according to RECIST 1.1.
- Duration of Overall Response (DoOR) [ Time Frame: Through study completion, an average of 42 months ]DoOR is defined as the time of initial response until documented tumor progression
- Duration of Clinical Benefit (DoCB) [ Time Frame: Through study completion, an average of 42 months ]DoCB is defined as the time of initial CB until documented tumor progression
- 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 ]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.
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): NCT04227327
|Contact: Marina E Cazzaniga, MD||+39 firstname.lastname@example.org|
|Contact: Monica Perez Gila||+39 email@example.com|