Phase IV Study of Abemaciclib and Endocrine Therapy in Hormone Receptor-Positive, HER2-Negative Advanced or Metastatic Breast Cancer with Digital Side Effect Management
- Trial ID
- 2024-511209-49-00
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this trial is to estimate **progression-free survival** (PFS) in patients with hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer. PFS is defined as the time from trial registration until disease progression or death from any cause, as per RECIST guideline version 1.1. This estimation will be conducted separately for two cohorts: patients who have not received prior endocrine treatment or progressed more than 12 months after adjuvant endocrine treatment, and those who progressed during or shortly after adjuvant endocrine treatment. This objective is clinically relevant as it provides insights into the efficacy of the combination of Abemaciclib and endocrine therapy in delaying disease progression.
Secondary objectives include: - Assessing the safety and tolerability of **Abemaciclib** through adverse events until disease progression or 30 days post-treatment. - Capturing patient-reported side effects daily via CANKADO PRO-React alongside regular adverse event documentation. - Evaluating laboratory findings. - Monitoring the frequency and duration of hospitalizations until disease progression. - Capturing patient-reported outcomes at baseline and specified timepoints. - Evaluating the efficacy of Abemaciclib in terms of clinical benefit rate, overall survival, objective response rate, time to response, and the number of patients with primary progression. - Assessing the response of known CNS metastases.
Participants
The clinical trial involves a total of **15 participants** who are exclusively **female** and aged **18 years or older**. The study population consists of patients diagnosed with **hormone receptor-positive HER2-negative locally advanced or metastatic breast cancer**. Participants were selected based on specific inclusion criteria, including the requirement for stable central nervous system metastases if present, and the ability to swallow oral medications. The trial does not include male subjects. Participants are required to have adequate bone marrow and organ function and must be willing to use the CANKADO digital health application to report side effects and patient-reported outcomes, although this is not mandatory. The trial population is characterized by a history of either no prior endocrine treatment or progression after adjuvant endocrine treatment, with or without prior adjuvant chemotherapy. Lifestyle considerations such as diet and physical activity are not specified. The trial does not include individuals who have received prior therapy for metastatic disease, except for a limited duration of first-line endocrine therapy. The study focuses on a vulnerable population, emphasizing the need for reliable participants who are available for the trial's duration and willing to follow trial procedures.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of a combination therapy involving **abemaciclib** and endocrine therapy in patients with hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer. This trial is structured as a randomized, double-blind, controlled study, ensuring that neither the participants nor the investigators are aware of the treatment assignments, thereby minimizing bias. The trial is expected to span a duration of approximately seven years, with an estimated end date in May 2029.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on specific inclusion criteria, such as stable CNS metastases and adequate bone marrow function. Following successful screening, participants will be randomized into one of two cohorts based on their prior endocrine treatment history. The trial will include regular follow-up visits to monitor progression-free survival (PFS), the primary endpoint, as well as secondary endpoints like overall survival (OS) and objective response rate (ORR). The end-of-study visit will occur at the conclusion of the treatment period or upon early termination.
The expected length of participant involvement is up to 36 months, corresponding to the maximum treatment period. Conditions that may lead to early termination from the study include disease progression, unacceptable toxicity, or withdrawal of consent. Participants are required to adhere to trial procedures, including the use of the CANKADO digital health application for reporting side effects, although its use is not mandatory for study participation. The trial aims to provide valuable insights into the management of side effects and the overall clinical benefit of the treatment regimen.
Treatment
The clinical trial involves the administration of several treatments, including both experimental and non-experimental medications. The experimental medication **Abemaciclib** is provided in the form of film-coated tablets, marketed under the name Verzenios. Each tablet contains 150 mg of the active substance, Abemaciclib, which is a chemical compound. The maximum daily dose is 300 mg, administered orally, with a maximum total dose of 150 mg per administration. The treatment period extends up to 36 months. Abemaciclib is classified under the ATC code L01EF03 and is used in combination with endocrine therapy for hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer.
Another experimental medication used in the trial is **Exemestane**, an aromatase inhibitor. Exemestane is administered orally in a pharmaceutical form identified as PHF00009MIG. The maximum daily dose is 25 mg, with the same amount as the maximum total dose per administration. The treatment duration is also up to 36 months. Exemestane is classified under the ATC code L02BG06.
The trial also includes the use of **Anastrozole**, another aromatase inhibitor, provided in a pharmaceutical form identified as PHF00082MIG. Anastrozole is administered orally with a maximum daily and total dose of 1 mg. The treatment period is up to 36 months, and it is classified under the ATC code L02BG03.
**Fulvestrant**, an antiestrogenic agent, is included as a non-experimental treatment. It is administered via intramuscular injection in a pharmaceutical form identified as PHF00231MIG. The maximum daily and total dose is 500 mg, with a treatment period extending up to 36 months. Fulvestrant is classified under the ATC code L02BA03.
Lastly, **Letrozole**, another aromatase inhibitor, is administered orally in a pharmaceutical form identified as PHF00082MIG. The maximum daily and total dose is 2.5 mg, with a treatment period of up to 36 months. Letrozole is classified under the ATC code L02BG04.
Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed treatment regimens. The trial aims to evaluate the efficacy and safety of these treatments in the specified patient population.
Efficacy
The efficacy of the clinical trial will be assessed primarily through the measurement of **progression-free survival (PFS)**. PFS is defined as the time from the date of trial registration until the occurrence of progressive disease or death from any cause, as determined by the investigator using the RECIST guideline version 1.1. If a patient has not experienced an event, PFS will be censored at the date of the last adequate tumor assessment. This primary endpoint will be calculated separately for two cohorts: patients with advanced/metastatic hormone receptor-positive HER2-negative breast cancer who either had no prior endocrine treatment or progressed more than 12 months after adjuvant endocrine treatment, and those who progressed while receiving adjuvant endocrine treatment or less than 12 months after its completion.
Secondary endpoints include **Overall Survival (OS)**, **Objective Response Rate (ORR)**, and **Clinical Benefit Rate (CBR)**. These parameters will provide additional insights into the efficacy of the treatment regimen. The trial will utilize the CANKADO digital health application to report side effects and patient-reported outcomes, although its use is not mandatory for participation. The trial is designed to ensure that all patients have adequate bone marrow and organ function, and are able to swallow oral medications. The trial will continue until the estimated end date of May 31, 2029, with efficacy assessments conducted at specified intervals throughout the study duration.
Inclusion and Exclusion Criteria
Inclusion 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 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
- 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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Not Recruiting | 06 May 2022 | 285 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Verzenios 150 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL USE | 300 | 36 | PRD6701108 |
FULVESTRANT | Other | PHF00231MIG | INTRAMUSCULAR INJECTION | 500 | 36 | SCP15544179 |
Verzenios 150 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL USE | 300 | 36 | PRD6834878 |
Verzenios 150 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL USE | 300 | 36 | PRD6715676 |
ANASTROZOLE | Other | PHF00082MIG | ORAL USE | 1 | 36 | SCP136961 |
Verzenios 150 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL USE | 300 | 36 | PRD6705392 |
Verzenios 150 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL USE | 300 | 36 | PRD6705387 |
LETROZOLE | Other | PHF00082MIG | ORAL USE | 2.5 | 36 | SCP1154118 |
Verzenios 150 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL USE | 300 | 36 | PRD6701111 |
EXEMESTANE | Other | PHF00009MIG | ORAL USE | 25 | 36 | SCP136386 |