Patients with… · Phase IV (2024-511209-49-00)

Start 26 Apr 2022 · Status Ongoing, recruitment ended · 1 EU/EEA countries · 55 sites

Overview

Sponsor-declared trial summary

Phase Therapeutic use (Phase IV)

Status Ongoing, recruitment ended

Participants planned 300

Countries 1

Sites 55

Patients with hormone receptor positive HER2 negative locally advanced or metastatic breast cancer

Key facts

Sponsor: Universitaetsklinikum Ulm AöR
Participant type: Patients
Age range: 18-64 years, 65+ years
Gender: Female
Therapeutic area: Diseases [C] - Neoplasms [C04]
Trial duration: 26 Apr 2022 → ongoing
Decision date (initial): 2024-08-30
Transition trial: Yes
Low-intervention: No
Rare-disease indication: No
Vulnerable population: Yes

External identifiers

EU CT number: 2024-511209-49-00
EudraCT number: 2021-000287-30
ClinicalTrials.gov: NCT05362760

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The primary objective of this trial is:
• Estimation of PFS, defined as the time from date of registration for the trial 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.
• PFS will be calculated separately for the following two cohorts:
Cohort 1: Patients with advanced/metastatic hormone receptor positive HER2 negative breast cancer who either had received no prior endocrine treatment or had progressed more than 12 months after the end of adjuvant endocrine treatment (with or without prior adjuvant chemotherapy)
Cohort 2: Patients with advanced/metastatic hormone receptor positive HER2 negative breast cancer who had progressed while receiving adjuvant endocrine treatment or less than 12 months after the end of adjuvant endocrine treatment (with or without prior adjuvant chemotherapy)

Secondary objectives 7

Safety and tolerability of Abemaciclib: Adverse Events assessed by investigator until PD or up to 30 days after end of trial treatment
Additional capture of Patient-Reported side effects on a daily basis via CANKADO PRO-React next to regular AE documentation and triggering of symptom self-reporting by significant changes in the EQ-VAS.
Evaluation of lab findings
Frequency and duration of hospitalizations until occurrence of disease progression
Patient reported outcome captured by app (or paper) at baseline and prespecified timepoints.
Efficacy of Abemaciclib: Clinical benefit rate, Overall survival, Objective response rate, Time to response, Number of patients with primary progression
Response of known CNS metastases

Conditions and MedDRA coding

Patients with hormone receptor positive HER2 negative locally advanced or metastatic breast cancer

Study design 1 period

#	Title	Allocation	Blinding	Roles blinded	Arms
1	Recruitment period This is a multinational “first line” phase IV trial to evaluate the safety, efficacy, QoL of treatment with Abemaciclib plus Aromatase Inhibitor (AI) or Fulvestrant. This trial is designed as an open-label, single-arm, phase IV trial.	Not Applicable	None		Single-arm with 2 cohorts: Cohort 1: (max 200 pts) it is assumed that the PFS is in a range similar to that reported in the MONARCH 3 trial for first line patients treated with Abemaciclib and a non-steroidal Aromatase Inhibitor (n = 328, median PFS = 28.2 months, 95% confidence interval 23.5 - tbd). As the upper limit of the 95% confidence interval is not available, the width of the 95% confidence interval is estimated as 11.5 months. Cohort 2: (max. 100 pts) it is assumed that the PFS is in a range similar to that reported in the MONARCH 2 trial for patients treated with Abemaciclib and Fulvestrant (n = 446, median PFS = 16.4 months, 95% confidence interval 14.4 – 19.3 months, width of the 95% confidence interval = 4.9 months). * Cohort limitation is lifted, if the recruitment ratio between Cohort 1 and Cohort 2 deviates strongly from the expected 2:1 ratio.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 20

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 HR+, HER2- breast cancer. The primary tumor has been confirmed as HER2-negative and hormone receptor positive breast cancer by histopathology, immunohistochemistry (IHC) or in-situ hybridization (ISH) according to local testing. If HER2 status of metastatic lesion is known this has to be HER2 negative.
To fulfill the requirement for HR+ disease, a breast cancer must express, by immunohistochemistry (IHC), at least one of the hormone receptors (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 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 ECOG scale
If 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 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, progestogen-only hormonal contraception associated with inhibition of ovulation , 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).
Patients who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 7-14 days (at discretion of the investigator) is required between end of radiotherapy and registration.
One of the following as defined by the RECIST v1. 1: a. 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. However, prior CT obtained as part of routine clinical case within 12 weeks prior to trial registration is also acceptable. b. 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.
The patient has adequate bone marrow and organ function evidenced within 14 days before trial registration for all of specific criteria (please refer to protocol)..
The patient is able to swallow oral medications.
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.
Negative pregnancy test before trial registration for women of childbearing 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.

Exclusion criteria 16

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 CDK 4/6 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 trial registration, except for first-line endocrine therapy in metastatic or locally advanced disease for max 3 months.
Radiotherapy within the last 7-14 days prior to registration
Patient has had major surgery within 14 days prior to trial registration.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

The primary endpoint of this trial is progression-free survival (PFS). PFS time is measured from trial registration until the date of investigator-determined objective progression as defined by RECIST v1.1, or death from any cause. Patients who have neither progressed nor died will be censored at the day of their last radiographic tumor assessment, if available, or date of trial registration if no post-initiation (that is, post-baseline) radiographic assessment is available.

Secondary endpoints 3

Overall Survival (OS)
Objective Response Rate (ORR)
Clinical Benefit Rate (CBR)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Organisation	City, country	Duties
Alcedis GmbH ORG-100012815	Giessen, Germany	On site monitoring, Code 12, Code 5, Data management, E-data capture
CANKADO GmbH ORL-000009374	München, Germany	Other, E-data capture

Country	MS status	Planned subjects	Sites
Germany	Ongoing, recruitment ended	285	55
Rest of world Switzerland	—	15	—

Type	Title	Version
Protocol (for publication)	D1_Minerva_trial protocol_clean_signed_redacted	3.1
Recruitment arrangements (for publication)	K1_MINERVA_recruitment arrangement	2.0
Subject information and informed consent form (for publication)	L1_Minerva_PatInfEwe_clean_redacted	3.1
Subject information and informed consent form (for publication)	L2_Minerva_Uebereignungsvertrag_Koerpermaterialien_V2_0_15-06-2023_redacted	2.0
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC Verzenios Filmtabletten	2
Synopsis of the protocol (for publication)	D1_MINERVA_Synopsis_V01_Lay Language_red	1

#	Type	Code	Submitted	Reference MS	Conclusion	Decision date
1	INITIAL	IN	2024-07-29	Germany	Acceptable 2024-08-26	2024-08-30
2	SUBSTANTIAL MODIFICATION	SM-1	2025-04-14	Germany	Acceptable 2025-06-05	2025-06-12
3	SUBSTANTIAL MODIFICATION	SM-2	2025-10-27	Germany	Acceptable	2025-11-11

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

Overview

Key facts

External identifiers

Trial design

Main objective

Secondary objectives 7

Conditions and MedDRA coding

Study design 1 period

Eligibility criteria

Inclusion criteria 20

Exclusion criteria 16

Endpoints

Primary endpoints 1

Secondary endpoints 3

Investigational products

Test 28

Auxiliary 4

Sponsors and contacts

Universitaetsklinikum Ulm AöR

Scientific contact point

Public contact point

Third parties 2

Locations

By country

Investigational sites

Country notifications

Results and documents

Documents 6 files

Application history

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