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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 (MINERVA)

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ClinicalTrials.gov Identifier: NCT05362760
Recruitment Status : Recruiting
First Posted : May 5, 2022
Last Update Posted : December 2, 2022
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Prof. W. Janni, University of Ulm

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


Condition or disease Intervention/treatment Phase
Hormone Receptor-positive Metastatic Breast Cancer HER2-negative Metastatic Breast Cancer Drug: Abemaciclib + Aromatase Inhibitor Drug: Abemaciclib + Fulvestrant Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
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
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 27, 2022
Estimated Primary Completion Date : April 2026
Estimated Study Completion Date : April 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Abemaciclib + Aromatase-Inhibitor
The patients will receive Abemaciclib in combination with an Aromatase-Inhibitor (either Anastrozole, Letrozole or exemestane)
Drug: Abemaciclib + Aromatase Inhibitor
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)
Other Name: Verzenios

Experimental: Abemaciclib + Fulvestrant
The patients will receive Abemaciclib in combination Fulvestrant
Drug: Abemaciclib + Fulvestrant
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)
Other Name: Verzenios




Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: 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 ]
    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.


Secondary Outcome Measures :
  1. Adverse Events [ Time Frame: From obtaining informed consent until progressive disease (PD) or up to 30 days after end of trial treatment ]
    Adverse Events assessed by investigator (type, frequency, severity (graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.5.0)), seriousness)

  2. Patient-reported side effects [ Time Frame: From first dose of study medication up to 30 days after end of trial treatment ]
    Additional capture of Patient-Reported side effects on a daily basis via CANKADO PRO-React (patient diary).

  3. Patient-reported global health status [ Time Frame: From first dose of study medication up to 30 days after end of trial treatment ]
    Daily self-assessment of global health status using the visual analogue scale (EQ-VAS, based on the EQ-5D questionnaire) via CANKADO. The EQ-VAS scale ranges from 0 (the worst possible health status to 100 (the best possible health status).

  4. Frequency of hospitalizations [ Time Frame: Time from date of registration for the trial through study completion (4 years after date of First Patient In) ]
    Frequency of hospitalizations during study treatment

  5. Patient reported European Organisation for Research and Treatment of Cancer Quality of Life C30 questionaire (EORTC QLQ-C30) [ Time Frame: At baseline, at 3, 6, 9, 12, 18, 24 months ]
    Patient reported quality of life as assessed with the EORTC QLQ-C30 questionnaire. The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

  6. Patient reported European Organisation for Research and Treatment of Cancer Quality of Life B23 breast cancer module questionaire (EORTC QLQ-BR23) [ Time Frame: At baseline, at 3, 6, 9, 12, 18, 24 months ]
    Patient reported quality of life as assessed with the EORTC QLQ-BR23 questionnaire. The QLQ-B23 breast cancer module incorporates five multi-item scales to assess systemic therapy side effects, arm symptoms, breast symptoms, body image and sexual functioning. In addition, single items assess sexual enjoyment, hair loss and future perspective. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

  7. Clinical benefit rate (CBR) [ Time Frame: Time from date of registration for the trial until 24 weeks of study treatment ]
    CBR defined as percentage of patients with complete response, partial response or stable disease

  8. Overall Survival (OS) [ Time Frame: Time from date of trial registration until date of death due to any cause, assessed up to 48 months ]
    Overall survival (OS) defined as the time from date of trial registration until date of death due to any cause. If a patient is not known to have died, survival is censored at the date of last contact.

  9. Objective Response Rate (ORR) [ Time Frame: Time from date of registration for the trial through study completion (4 years after date of First Patient In) ]
    ORR defined as percentage of patients with complete or partial response as defined by RECIST 1.1

  10. Number of patients with primary progression [ Time Frame: Time from date of registration for the trial until first imaging after 12 weeks ]
    Number of patients with primary progression, defined as number of patients with disease recurrence within 12 weeks after recruitment.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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 locoregionally 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. 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. Previous adjuvant endocrine therapy and (neo)adjuvant chemotherapy is allowed
  13. 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.
  14. 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.
  15. 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.
  16. 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
  17. The patient is able to swallow oral medications
  18. Willingness to use the provided CANKADO digital health application to report side effects and patient reported outcomes
  19. Negative pregnancy test before trial registration for women of child-bearing potential and highly effective contraception if the risk of conception exists

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
  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
  8. Treatment with any other investigational agents within four weeks prior to trial registration
  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
  15. Radiotherapy within the last 14 days prior to registration

Information from the National Library of Medicine

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): NCT05362760


Contacts
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Contact: Natalie Uhl +49 731 500 58652 natalie.uhl@uniklinik-ulm.de

Locations
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Sponsors and Collaborators
Prof. W. Janni
Eli Lilly and Company
Investigators
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Principal Investigator: Brigitte Rack, Prof. Dr. Department of Gynecology and Obstetrics, University Hospital Ulm, Germany
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Responsible Party: Prof. W. Janni, Director of the Department of Obstetrics and Gynecology, University of Ulm
ClinicalTrials.gov Identifier: NCT05362760    
Other Study ID Numbers: MINERVA
2021-000287-30 ( EudraCT Number )
First Posted: May 5, 2022    Key Record Dates
Last Update Posted: December 2, 2022
Last Verified: December 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Prof. W. Janni, University of Ulm:
hormone receptor-positive
HER2-negative
locally advanced/metastatic breast cancer
abemaciclib
endocrine therapy
phase IV
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Fulvestrant
Aromatase Inhibitors
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action