Combination of Abemaciclib and Endocrine Therapy in Hormone Receptor Positive HER2 Negative Locally Advanced or Metastatic Breast Cancer With Focus on Digital Side Effect Management

NCT05362760 | Recruiting Phase 4 FDA Drug

• 2 other identifiers: MINERVA2021-000287-30
• Study Type: interventional
• Target: 300
• Locations: 2 countries
• Sites: 54

Brief Summary

The MINERVA Trial aims to evaluate safety, efficacy and quality of life (QoL) for the combination of Abemaciclib with an Aromatase Inhibitor or Fulvestrant in pre- and postmenopausal patients with metastatic hormone receptor positive HER2 negative breast cancer in the first line setting. Side effect monitoring and patient reported outcomes will be captured using the web- and app-based CANKADO digital health application. Via this user-friendly tool the patients can document their therapy side effects (e.g. diarrhea) and outcomes on a day-to-day basis. The capturing of side effects using the digital health application will be done additionally to the regular AE documentation. Furthermore, translational research objectives of this trial include the investigation of biomarkers (ct-DNA, germline DNA) to evaluate whether they can give insights into the reasons for response, intrinsic or acquired resistance to the combined endocrine

Conditions

Hormone Receptor-positive Metastatic Breast Cancer; HER2-negative Metastatic Breast Cancer

Keywords

hormone receptor-positive; HER2-negative; locally advanced/metastatic breast cancer; abemaciclib; endocrine therapy; phase IV

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  PFS, defined as the time from date of trial registration until progressive disease (PD) or death from any cause, whichever comes first (as defined by RECIST guideline version 1.1). If a patient has not had an event, PFS is censored at the date of last adequate tumor assessment.

  Time from date of trial registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months

Secondary Outcomes (10)

• Adverse Events

  From obtaining informed consent until progressive disease (PD) or up to 30 days after end of trial treatment

• Patient-reported side effects

  From first dose of study medication up to 30 days after end of trial treatment

• Patient-reported global health status

  From first dose of study medication up to 30 days after end of trial treatment

• Frequency of hospitalizations

  Time from date of registration for the trial through study completion (4 years after date of First Patient In)

• Patient reported European Organisation for Research and Treatment of Cancer Quality of Life C30 questionaire (EORTC QLQ-C30)

  At baseline, at 3, 6, 9, 12, 18, 24 months

Study Arms (2)

Abemaciclib + Aromatase-Inhibitor

EXPERIMENTAL

The patients will receive Abemaciclib in combination with an Aromatase-Inhibitor (either Anastrozole, Letrozole or exemestane)

Drug: Abemaciclib + Aromatase Inhibitor

Abemaciclib + Fulvestrant

EXPERIMENTAL

The patients will receive Abemaciclib in combination Fulvestrant

Drug: Abemaciclib + Fulvestrant

Interventions

Abemaciclib + Aromatase Inhibitor DRUG

Abemaciclib 150 mg orally every 12 hours plus Aromatase Inhibitor ( Anastrozole 1 mg, Letrozole 2.5 mg or exemestane 25 mg orally every 24 hours on Days 1 to 28 of a 28-day cycle)

Also known as: Verzenios

Abemaciclib + Aromatase-Inhibitor

Abemaciclib + Fulvestrant DRUG

Abemaciclib 150 mg orally every 12 hours plus Fulvestrant (500 mg intramuscularly on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond on Day 1 of a 28-day cycle)

Also known as: Verzenios

Abemaciclib + Fulvestrant

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients will be included in the trial only if they meet all the following criteria:
• Have given written informed consent prior to any trial-specific procedures
• Are reliable, willing to be available for the duration of the trial and are willing to follow trial procedures
• Are female and aged ≥ 18 years
• Diagnosis of hormone receptor positive (HR+), HER2- breast cancer. Although not required as a protocol procedure, metastatic disease should be considered for biopsy whenever possible to reassess HR and HER2 status if clinically indicated.
• To fulfill the requirement for HR+ disease, a breast cancer must express, by immunohistochemistry (IHC), at least one of the hormone receptors (estrogen receptor \[ER\], progesterone receptor \[PgR\]) as defined in the relevant American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) Guidelines (Hammond et al. 2010).
• To fulfill the requirement of HER2- disease, a breast cancer must not demonstrate, at initial diagnosis or upon subsequent biopsy, overexpression of HER2 by either IHC or in-situ hybridization (ISH) as defined in the relevant ASCO/CAP guidelines (Wolff et al. 2013).
• Have locally advanced recurrent disease not amenable to resection or radiation therapy with curative intent or metastatic disease
• Indication for endocrine based therapy in the metastatic setting
• Have a performance status (PS) of ≤2 on the Eastern Cooperative Oncology Group (ECOG) scale
• If central nervous system (CNS) metastases are known these have to be stable (radiotherapy finished for more than 14 days ago, no required steroid medication with more than 4 mg Dexamethasone per day)
• Pre- and postmenopausal patients are allowed. Postmenopausal is defined as no menses for 12 months without an alternative medical cause. Women of Childbearing Potential (WOCBP, defined as not postmenopausal and not surgically or congenitally sterile) whose male partners are potentially fertile (e.g. no vasectomy) must use highly effective contraception methods for the duration of the trial and for at least 3 weeks after last dose of drugs used in the trial.Women of childbearing potential must use highly effective contraception methods for two years after the last dose of fulvestrant. Highly effective birth control methods that results in a failure rate of less than 1% per year include combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner. Sexual abstinence is only considered a highly effective method if defined as refraining from heterosexual intercourse in the defined period. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the trial and the preferred and usual lifestyle of the patient.
• No prior therapy for metastatic disease (except for first line endocrine therapy for maximal 3 months prior to start of abemaciclib therapy and if no progress occurred before study entry)
• Previous adjuvant endocrine therapy and (neo)adjuvant chemotherapy is allowed
• Patients who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or ≤ Grade 2 peripheral neuropathy prior to registration. A washout period of at least 21 days is required between last chemotherapy dose and registration (provided the patient did not receive radiotherapy).

You may not qualify if:

• Patients will be included in the trial only if they meet none of the following criteria:
• Visceral crisis or life expectancy \< 6 months
• History of hypersensitivity reactions attributed to Abemaciclib or to other components of drug formulation
• Prior treatment with chemotherapy in the metastatic setting or endocrine therapy in the metastatic setting (except for first line endocrine therapy in metastatic or locally advanced disease for maximal 3 months prior to start of abemaciclib therapy and if no progress occurred before study entry)
• Patient not eligible for endocrine based therapy
• Any concurrent severe, uncontrolled systemic disease, social or psychiatric condition that might interfere with the planned treatment and with the patient's adherence to the protocol
• The patient has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this trial (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \[e.g. estimated creatinine clearance \<30ml/min\], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
• Prior treatment with a CDK4/6 inhibitor for metastatic or locally advanced disease (first-line treatment with a CDK 4/6 inhibitor (Ribociclib/Palbociclib) in the metastatic setting is allowed only if terminated due to toxicity after max 3 months and no progression occurred before study entry. Prior treatment with a CDK 4/6 inhibitor in the neo-/adjuvant setting is allowed.)
• \. Treatment with any other investigational agents within four weeks or 5 half-lives prior to trial registration, whichever is longer
• 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.
• Females who are pregnant or lactating
• Legal incapacity or limited legal capacity
• History of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years.
• The patient has active systemic bacterial infection (requiring intravenous \[IV\] antibiotics at time of initiating trial treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C \[for example, hepatitis B surface antigen positive\]. Screening is not required for enrollment.
• Prior systemic anti-cancer therapy within the last 21 days prior to start of trial treatment except for first-line endocrine therapy in metastatic or locally advanced disease (see above)

Sponsors & Collaborators

• Prof. Wolfgang Janni: lead
• Eli Lilly and Company: collaborator

Study Sites (54)

Kliniken Ostalb gkAöR

Aalen, Germany

RECRUITING

Klinikum St. Marien Kommunalunternehmen - AöR Der Stadt Amberg

Amberg, Germany

RECRUITING

Klinikum Aschaffenburg-Alzenau gGmbH

Aschaffenburg, Germany

RECRUITING

Gemeinschaftspraxis Dr. Heinrich / Dr. Bangerter

Augsburg, Germany

RECRUITING

Universitätsklinikum Augsburg A.d.ö.R

Augsburg, Germany

RECRUITING

MediOnko-Institut GbR

Berlin, Germany

RECRUITING

Hämatologikum Biberach

Biberach, Germany

RECRUITING

Gynäkologisches Zentrum Bonn - Friedensplatz

Bonn, Germany

RECRUITING

Studien GbR Braunschweig

Braunschweig, Germany

RECRUITING

Hämato-Onkologische Praxis im Medicum

Bremen, Germany

RECRUITING

St. Elisabeth-Krankenhaus GmbH

Cologne, Germany

RECRUITING

Onkologisches Zentrum Donauwörth

Donauwörth, Germany

RECRUITING

Gemeinschaftspraxis

Dresden, Germany

RECRUITING

Onkozentrum Dresden

Dresden, Germany

RECRUITING

MVZ Medical Center Düsseldorf GmbH

Düsseldorf, Germany

RECRUITING

Universitätsklinikum Düsseldorf

Düsseldorf, Germany

RECRUITING

Internistische Praxis Ehingen

Ehingen, Germany

RECRUITING

Universitätsklinikum Erlangen

Erlangen, Germany

RECRUITING

St. Antonius-Hospital

Eschweiler, Germany

RECRUITING

Centrum für Hämatologie und Onkologie Bethanien

Frankfurt, Germany

RECRUITING

Universitätsklinikum Freiburg

Freiburg im Breisgau, Germany

RECRUITING

Krankenhäuser Landkreis Freudenstadt gGmbH

Freudenstadt, Germany

RECRUITING

Internistische Gemeinschaftspraxis

Friedrichshafen, Germany

RECRUITING

Klinikum Garmisch-Partenkirchen GmbH

Garmisch-Partenkirchen, Germany

RECRUITING

Main-Kinzig-Kliniken gGmbH Gelnhausen

Gelnhausen, Germany

RECRUITING

Gemeinschaftspraxis und Tagesklinik Halle

Halle, Germany

RECRUITING

Albertinen-Krankenhaus

Hamburg, Germany

RECRUITING

Sana Klinikum Hameln-Pyrmont

Hamelin, Germany

RECRUITING

Frauenärzte am Bahnhofsplatz

Hildesheim, Germany

RECRUITING

ViDia Christliche Kliniken Karlsruhe

Karlsruhe, Germany

RECRUITING

Klinikum Kassel GmbH

Kassel, Germany

RECRUITING

Klinikverbund Kempten-Oberallgäu gGmbH

Kempten, Germany

RECRUITING

Klinikum Konstanz

Konstanz, Germany

RECRUITING

ZAGO- Zentrum für ambulante gynäkologische Onkologie

Krefeld, Germany

RECRUITING

Krankenhausgesellschaft St. Vincenz mbH

Limburg, Germany

RECRUITING

Praxis für gynäkologische Onkologie / Prof. Dr. med. Ulrike Nitz / Raquel von Schumann

Mönchengladbach, Germany

RECRUITING

Kliniken Ostalb gkAöR, Stauferklinikum Schwäbisch Gmünd

Mutlangen, Germany

RECRUITING

LMU - Klinikum der Universität München

München, Germany

RECRUITING

München Klinik gGmbH Harlaching

München, Germany

RECRUITING

TZN-Tumorzentrum Niederrhein GmbH

Neuss, Germany

RECRUITING

Klinikum Nürnberg Nord

Nuremberg, Germany

RECRUITING

medius KLINIK NÜRTINGEN

Nürtingen, Germany

RECRUITING

Praxis Dr. Guth

Plauen, Germany

RECRUITING

Klinikum Ernst von Bergmann gGmbH

Potsdam, Germany

RECRUITING

Klinikum Rheine

Rheine, Germany

RECRUITING

GPR Gesundheits- und Pflegezentrum Rüsselsheim gGmbH

Rüsselsheim am Main, Germany

RECRUITING

Diakoneo Diak-Klinikum Schwäbisch Hall gGmbH

Schwäbisch Hall, Germany

RECRUITING

Clinical Research Stolberg GmbH

Stolberg, Germany

RECRUITING

Gynäkologie Kompetenzzentrum Stralsund

Stralsund, Germany

RECRUITING

Universitätsfrauenklinik Tübingen

Tübingen, Germany

RECRUITING

University Hospital Ulm Gynecology/Obstetrics

Ulm, Germany

RECRUITING

St. Josefs-Hospital

Wiesbaden, Germany

RECRUITING

Spital Wallis

Brig, Switzerland

RECRUITING

Kantonsspital St. Gallen

Sankt Gallen, Switzerland

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

abemaciclib; Aromatase Inhibitors; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones

Study Officials

• Brigitte Rack, Prof. Dr.

  Department of Gynecology and Obstetrics, University Hospital Ulm, Germany

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Natalie Uhl

CONTACT

+49 731 500 58652; natalie.uhl@uniklinik-ulm.de

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of the Department of Obstetrics and Gynecology

Model Details: Non-randomized phase 4 clinical trial with two arms (cohorts), i.e. abemaciclib plus aromatase inhibitor or abemaciclib plus fulvestrant, with patient assignment to the arms by physician's choice

Study Record Dates

• First Submitted: April 5, 2022
• First Posted: May 5, 2022
• Study Start: April 27, 2022
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2029
• Last Updated: May 16, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CH (2); DE (52)