Clinical trial NCT05362760: 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
Official title: 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. The MINERVA Trial - A Phase IV Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
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
Lead sponsor: University of Ulm
Sponsor class: OTHER
Collaborators: name: Eli Lilly and Company
First posted: 2022-05-05
Enrollment: 300
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

Patients will be included in the trial only if they meet all the following criteria:

1. Have given written informed consent prior to any trial-specific procedures
2. Are reliable, willing to be available for the duration of the trial and are willing to follow trial procedures
3. Are female and aged ≥ 18 years
4. 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.
5. 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).
6. 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).
7. Have locally advanced recurrent disease not amenable to resection or radiation therapy with curative intent or metastatic disease
8. Indication for endocrine based therapy in the metastatic setting
9. Have a performance status (PS) of ≤2 on the Eastern Cooperative Oncology Group (ECOG) scale
10. 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)
11. 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.
12. 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)
13. Previous adjuvant endocrine therapy and (neo)adjuvant chemotherapy is allowed
14. 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).
15. Patients who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and registration.
16. One of the following as defined by the RECIST v1. 1 (see Attachment 15.5):

    1. Measurable disease. At least one measurable lesion assessable using standard techniques by Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1). Tumor evaluation according to RECIST version 1.1 (based on local assessment) has to be performed within 28 days before trial registration.
    2. Nonmeasurable bone-only disease (must be evaluable, but not necessarily measurable by RECIST). Nonmeasurable bone-only disease may include any of the following: blastic bone lesion, lytic bone lesions without a measurable soft tissue component, or mixed lytic-blastic bone lesions without a measurable soft tissue component.
17. The patient has adequate bone marrow and organ function evidenced by the following laboratory results: absolute neutrophil count (ANC) ≥ 1.5 × 109/L, Platelet count ≥ 100 × 109/L, Hemoglobin ≥ 8 g/dL, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.0 × ULN (≤ 3 x ULN in case of liver metastases), Total Bilirubin ≤ 1.5 × ULN (with Gilbert's syndrome max. 2 x ULN), Serum Creatinine ≤ 2.0 mg/dl or 177µmol/L, Coagulation: International Normalized Ratio (INR) ≤ 1,5
18. The patient is able to swallow oral medications
19. Willingness to use the provided CANKADO digital health application to report side effects and patient reported outcomes (The use of the CANKADO app is not mandatory for study participation, but is strongly recommended)
20. Negative pregnancy test before trial registration for women of child-bearing potential and highly effective contraception if the risk of conception exists and a negative serum pregnancy test within 7 days after the first dose of trial treatment. Pregnancy tests should be performed in premenopausal patients according to local standard

Exclusion Criteria:

Patients will be included in the trial only if they meet none of the following criteria:

1. Visceral crisis or life expectancy \< 6 months
2. History of hypersensitivity reactions attributed to Abemaciclib or to other components of drug formulation
3. 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)
4. Patient not eligible for endocrine based therapy
5. 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
6. 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).
7. 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.)
8. 8. Treatment with any other investigational agents within four weeks or 5 half-lives prior to trial registration, whichever is longer
9. 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.
10. Females who are pregnant or lactating
11. Legal incapacity or limited legal capacity
12. 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.
13. 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.
14. 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)
15. Radiotherapy within the last 14 days prior to registration
16. Patient has had major surgery within 14 days prior to trial registration.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 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:
measure: Adverse Events
timeFrame: From obtaining informed consent until progressive disease (PD) or up to 30 days after end of trial treatment
measure: Patient-reported side effects
timeFrame: From first dose of study medication up to 30 days after end of trial treatment
measure: Patient-reported global health status
timeFrame: From first dose of study medication up to 30 days after end of trial treatment
measure: Frequency of hospitalizations
timeFrame: Time from date of registration for the trial through study completion (4 years after date of First Patient In)
measure: Patient reported European Organisation for Research and Treatment of Cancer Quality of Life C30 questionaire (EORTC QLQ-C30)
timeFrame: At baseline, at 3, 6, 9, 12, 18, 24 months
measure: Patient reported European Organisation for Research and Treatment of Cancer Quality of Life B23 breast cancer module questionaire (EORTC QLQ-BR23)
timeFrame: At baseline, at 3, 6, 9, 12, 18, 24 months
measure: Clinical benefit rate (CBR)
timeFrame: Time from date of registration for the trial until 24 weeks of study treatment
measure: Overall Survival (OS)
timeFrame: Time from date of trial registration until date of death due to any cause, assessed up to 48 months
measure: Objective Response Rate (ORR)
timeFrame: Time from date of registration for the trial through study completion (4 years after date of First Patient In)
measure: Number of patients with primary progression
timeFrame: Time from date of registration for the trial until first imaging after 12 weeks
Other outcomes:
Locations:
city: Aalen
country: Germany
facility: Kliniken Ostalb gkAöR
city: Amberg
country: Germany
facility: Klinikum St. Marien Kommunalunternehmen - AöR Der Stadt Amberg
city: Aschaffenburg
country: Germany
facility: Klinikum Aschaffenburg-Alzenau gGmbH
city: Augsburg
country: Germany
facility: Gemeinschaftspraxis Dr. Heinrich / Dr. Bangerter
city: Augsburg
country: Germany
facility: Universitätsklinikum Augsburg A.d.ö.R
city: Berlin
country: Germany
facility: MediOnko-Institut GbR
city: Biberach
country: Germany
facility: Hämatologikum Biberach
city: Bonn
country: Germany
facility: Gynäkologisches Zentrum Bonn - Friedensplatz
city: Braunschweig
country: Germany
facility: Studien GbR Braunschweig
city: Bremen
country: Germany
facility: Hämato-Onkologische Praxis im Medicum
city: Donauwörth
country: Germany
facility: Onkologisches Zentrum Donauwörth
city: Dresden
country: Germany
facility: Gemeinschaftspraxis
city: Dresden
country: Germany
facility: Onkozentrum Dresden
city: Düsseldorf
country: Germany
facility: MVZ Medical Center Düsseldorf GmbH
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf
city: Ehingen
country: Germany
facility: Internistische Praxis Ehingen
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
city: Eschweiler
country: Germany
facility: St. Antonius-Hospital
city: Frankfurt
country: Germany
facility: Centrum für Hämatologie und Onkologie Bethanien
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
city: Freudenstadt
country: Germany
facility: Krankenhäuser Landkreis Freudenstadt gGmbH
city: Friedrichshafen
country: Germany
facility: Internistische Gemeinschaftspraxis
city: Garmisch-Partenkirchen
country: Germany
facility: Klinikum Garmisch-Partenkirchen GmbH
city: Gelnhausen
country: Germany
facility: Main-Kinzig-Kliniken gGmbH Gelnhausen
city: Halle
country: Germany
facility: Gemeinschaftspraxis und Tagesklinik Halle
city: Hamburg
country: Germany
facility: Albertinen-Krankenhaus
city: Hameln
country: Germany
facility: Sana Klinikum Hameln-Pyrmont
city: Hildesheim
country: Germany
facility: Frauenärzte am Bahnhofsplatz
city: Karlsruhe
country: Germany
facility: ViDia Christliche Kliniken Karlsruhe
city: Kassel
country: Germany
facility: Klinikum Kassel GmbH
city: Kempten
country: Germany
facility: Klinikverbund Kempten-Oberallgäu gGmbH
city: Konstanz
country: Germany
facility: Klinikum Konstanz
city: Krefeld
country: Germany
facility: ZAGO- Zentrum für ambulante gynäkologische Onkologie
city: Köln
country: Germany
facility: St. Elisabeth-Krankenhaus GmbH
city: Limburg
country: Germany
facility: Krankenhausgesellschaft St. Vincenz mbH
city: Mutlangen
country: Germany
facility: Kliniken Ostalb gkAöR, Stauferklinikum Schwäbisch Gmünd
city: Mönchengladbach
country: Germany
facility: Praxis für gynäkologische Onkologie / Prof. Dr. med. Ulrike Nitz / Raquel von Schumann
city: München
country: Germany
facility: LMU - Klinikum der Universität München
city: München
country: Germany
facility: München Klinik gGmbH Harlaching
city: Neuss
country: Germany
facility: TZN-Tumorzentrum Niederrhein GmbH
city: Nürnberg
country: Germany
facility: Klinikum Nürnberg Nord
city: Nürtingen
country: Germany
facility: medius KLINIK NÜRTINGEN
city: Plauen
country: Germany
facility: Praxis Dr. Guth
city: Potsdam
country: Germany
facility: Klinikum Ernst von Bergmann gGmbH
city: Rheine
country: Germany
facility: Klinikum Rheine
city: Rüsselsheim
country: Germany
facility: GPR Gesundheits- und Pflegezentrum Rüsselsheim gGmbH
city: Schwäbisch Hall
country: Germany
facility: Diakoneo Diak-Klinikum Schwäbisch Hall gGmbH
city: Stolberg
country: Germany
facility: Clinical Research Stolberg GmbH
city: Stralsund
country: Germany
facility: Gynäkologie Kompetenzzentrum Stralsund
city: Tübingen
country: Germany
facility: Universitätsfrauenklinik Tübingen
city: Ulm
country: Germany
facility: University Hospital Ulm Gynecology/Obstetrics
city: Wiesbaden
country: Germany
facility: St. Josefs-Hospital
city: Brig
country: Switzerland
facility: Spital Wallis
city: Saint Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
Study officials:
affiliation: Department of Gynecology and Obstetrics, University Hospital Ulm, Germany
name: Brigitte Rack, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: