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

Advanced Breast Cancer Clinical Trial

— 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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04227327
• Other study ID #: HERMIONE-7
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 7, 2020
• Est. completion date: December 2023

Study information

• Verified date: April 2023
• Source: University of Milano Bicocca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 31
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Abemaciclib
Abemaciclib will be administered orally at 150 mg twice daily
• Aromatase Inhibitors
Letrozole 2,5 mg daily or Anastrozole 1 mg daily

Locations

Country	Name	City	State
Italy	AOU ospedali riuniti Ancona clinica oncologica	Ancona
Italy	ASL di Asti D.H. - oncologia	Asti
Italy	IRCCS Istituto Oncologico Giovanni Paolo II	Bari
Italy	Ospedale Monsignor Dimiccoli	Barletta
Italy	ULSS 1 Belluno Ospedale San Martino	Belluno
Italy	ASST degli Spedali civili	Brescia
Italy	ASL AL - Ospedale "Santo Spirito"	Casale Monferrato
Italy	ASST Lariana	Como
Italy	ASST Cremona Istituti ospitalieri Cremona	Cremona
Italy	AO S. Croce e Carle Ospedale di Insegnamento	Cuneo
Italy	ASST Monza, Ospedale di Desio	Desio
Italy	ULSS1 Dolomiti - Ospedale di Feltre	Feltre
Italy	Azienda Ospedaliero-Universitaria di Ferrara	Ferrara
Italy	Azienda ospedaliera S. Antonio abate	Gallarate
Italy	AUSL di Reggio Emilia clinica oncologica Guastalla	Guastalla
Italy	Azienda ospedaliera cardinale Giovanni Panico	Lecce
Italy	ASST Lecco	Lecco
Italy	AUSL Toscana Nord Ovest Livorno	Livorno
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS	Meldola
Italy	ASST Monza, Ospedale San Gerardo	Monza
Italy	Istituto Oncologico Veneto IRCCS	Padova
Italy	Ospedale La Maddalena	Palermo
Italy	Policlinico universitario di Palermo - oncologia medica	Palermo
Italy	IRCCS Fondazione Salvatore Maugeri	Pavia
Italy	AUSL di Piacenza Ospedale "Guglielmo da Saliceto"	Piacenza
Italy	Arcispedale S. Maria nuova	Reggio Emilia
Italy	ASST Rhodense ospedale di circolo Rho	Rho
Italy	AUSL Romagna ospedale di Rimini	Rimini
Italy	Istituto Nazionale dei tumori Regina Elena- oncologia medica A	Roma
Italy	Istituto Nazionale dei tumori Regina Elena- oncologia medica B	Roma
Italy	Humanitas research hospital	Rozzano
Italy	Ospedale Ruggi d'Aragona	Salerno
Italy	ASST Valle Olona P.O. SARONNO	Saronno
Italy	A.O.U. Città della Salute e della Scienza di Torino	Torino
Italy	AOU Città della salute e della scienza - Breast Unit	Torino
Italy	ASL Torino presidio ospedaliero Martini	Torino
Italy	APSS provincia autonoma di Trento Ospedale di Trento	Trento
Italy	ASST Settelaghi Varese	Varese
Italy	Azienda Ospedaliera Universitaria Integrata Verona	Verona

Sponsors (1)

Lead Sponsor	Collaborator
University of Milano Bicocca

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical benefit rate (CBR) in HD-FUL pre-treated MBC patients treated with Abemaciclib + aromatase inhibitors (letrozole or anastrozole)	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.	At 6 months from treatment initiation
Secondary	Time To Progression (TTP)	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	Through study completion, an average of 42 months
Secondary	Overall Response Rate (ORR)	ORR is defined as the proportion of patients with best overall response of CR or PR) according to RECIST 1.1.	Through study completion, an average of 42 months
Secondary	Duration of Overall Response (DoOR)	DoOR is defined as the time of initial response until documented tumor progression	Through study completion, an average of 42 months
Secondary	Duration of Clinical Benefit (DoCB)	DoCB is defined as the time of initial CB until documented tumor progression	Through study completion, an average of 42 months
Secondary	To assess the safety profile of Abemaciclib in association with aromatase inhibitors (letrozole or anastrozole)	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.	Through study completion, an average of 42 months