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JOURNAL ONKOLOGIE – STUDIE
Abemacare

Abemaciclib in Combination With Endocrine Therapy as First Line Therapy in Metastatic Breast Cancer Patients With Symp-tomatic Visceral Metastases or High Tumor Burden

Rekrutierend

NCT-Nummer:
NCT04681768

Studienbeginn:
Dezember 2020

Letztes Update:
11.01.2021

Wirkstoff:
Abemaciclib

Indikation (Clinical Trials):
Breast Neoplasms

Geschlecht:
Frauen

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Technische Universität München

Collaborator:
Eli Lilly and Company

Studienleiter

Johannes Ettl, MD
Study Chair
Klinikum rechts der Isar der TU München, Klinik und Poliklinik für Frauenheilkunde

Kontakt

Studienlocations
(1 von 1)

Klinikum rechts der Isar der TU München, Klinik und Poliklinik für Frauenheilkunde
81675 Munich
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Johannes Ettl, MD
E-Mail: johannes.ettl@tum.de
» Ansprechpartner anzeigen

Studien-Informationen

Detailed Description:

Against the above discussed background there is a clear rationale to further collect real

world data confirming that the use of endocrine based therapy in metastatic breast cancer is

beneficial for the patient cohort with symptomatic visceral metastases and high tumor burden.

Data recently presented, showed that Abemaciclib in combination with Letrozole leads to

substantial reduction in tumor size after only two cycles of therapy. Since Abemaciclib is

the only CDK4/6-inhibitor that can be given "steady state" without a "one-week-off"-period

and since there has been beginning evidence that Abemaciclib is penetrating the blood brain

barrier in patients with brain metastases, it seems reasonable to choose Abemaciclib in

combination with endocrine therapy for an observational study whose objective will be to

collect efficacy data within clinical routine on Abemaciclib in combination with endocrine

therapy within a cohort of ERpos/HER2neg breast cancer patients with symptomatic visceral

metastases or high tumor burden.

LDH-levels above 400 U/l as well as abnormal levels of breast cancer specific tumor markers

CA 15-3 and CEA have been proven to correlate with disease extent in metastatic breast cancer

and thus can be used to identify metastatic breast cancer patients with high tumor burden.

Recently it could be shown that circulating tumor DNA (ctDNA) bares greater correlation with

changes in tumor burden than CA 15-3 and can provide the earliest measure of treatment

response in women with metastatic breast cancer. This warrants further research to evaluate

ctDNA as a tool for measuring early tumor response in MBC patients.

Translational research part:

In the era of personalized cancer therapy, testing for genetic alterations has become an

essential tool in clinical practice. It allows clinicians to identify patients who are most

likely to benefit from molecularly targeted treatments. Currently, evaluation of response to

targeted drugs is largely based on imaging (CT or MRT), an approach unable to reveal

mechanistic details on individual treatment effects. Sequential biopsies of tumors and their

molecular analysis could yield additional information, but repetitive sampling of tissue that

is representative and adequate in quantity and quality is rarely feasible, especially in the

metastatic disease setting.

Liquid biopsies (LBs) represent a minimally-invasive alternative of great potential in this

setting. Although recent technical advances allow very sensitive detection of LB-based tumor

biomarkers, only few LB assays have yet entered into clinical routine.

Blood plasma samples from patients treated with Abemaciclib will be analyzed to identify

predictive cell-free (cf) DNA-based biomarkers as indicators for treatment efficacy and early

detection of resistance. To this end, cfDNA will be screened for mutations using a targeted

next-generation sequencing panel (AVENIO ctDNA Expanded Kit, Roche). This panel is covering a

total of 192 kb and consists of 77 genes, including those currently in the US National

Comprehensive Cancer Network guidelines as well as emerging biomarkers currently being

investigated in clinical trials.

For each plasma sample, concentration of cfDNA as well as presence and allelic frequencies of

tumor mutations will be measured. Additionally, associations with progression-free survival

and overall survival will be evaluated using Cox regression models. Clinical variables will

be used as covariates in multivariable regression models to evaluate the independence of the

LB-based biomarkers.

As a result, the investigators hope to identify minimally invasive LB-based biomarkers for

serial monitoring of metastatic breast cancer patients. These biomarkers could add to the

prediction of therapy response as well as the early detection of therapy resistance towards

endocrine therapy and Abemaciclib.

Ein-/Ausschlusskriterien

Inclusion Criteria:

1. Age ≥18 years

2. Female patients who will start endocrine therapy (aromatase inhibitor or Fulvestrant)

in combination with Abemaciclib as first line treatment for metastatic breast cancer

within clinical routine

3. Signed informed consent

4. Life expectancy greater or equal to 12 weeks

5. Histologically proven diagnosed estrogen receptor positive, HER2 negative metastatic

breast cancer not amenable to curative treatment

6. Radiographic evidence of measurable or evaluable visceral disease

7. Visceral involvement must fulfil one of the following criteria:

1. Presence of any clinical sign or symptom from visceral disease (at least one of

the following: pleural effusion, ascites, abdominal pain from liver or peritoneal

metastases, dyspnea from pleural effusion or lymphangiosis of the lung, elevated

liver enzymes (> 2x ULN), elevated bil-irubin)

2. Signs of high tumor burden (at least one of the following: LDH >399 U/l with K in

normal range, abnormal (> 2x ULN) CEA or CA15-3 level, radiographic signs of

lymphangiosis of the lung, cytologically proven bone marrow infiltration)

Exclusion Criteria:

1. Contraindications for treatment with Abemaciclib, aromatase inhibitor or Fulvestrant

according to current SmPC

2. Prior first line therapy (endocrine or chemotherapy) for metastatic breast cancer

3. Prior treatment with any CDK4/6 inhibitor (or participation in any CDK4/6 inhibitor

clinical trial for which treatment assignment is still blinded)

4. Bone-only disease

5. Participation in clinical trials using an IMP within the last four weeks prior to

inclusion (ICF)

6. Treatment with a drug that has not received regulatory approval for any indication

within 28 days of initiation of study treatment for a non-myelosuppressive or

myelosuppressive agent, respectively

7. Patients who are pregnant or breast-feeding

Studien-Rationale

Primary outcome:

1. objective response rate (ORR) while being on study treatment using RECIST V1.1. (Time Frame - Maximum time frame will be 48 months):
Aim of this observational study is to collect efficacy data within clinical routine on Abemaciclib in combi-nation with endocrine therapy in estrogen receptor (ER) positive, HER2 negative metastatic breast cancer patients with symptomatic visceral disease or disease with high tumor burden.



Secondary outcome:

1. ORR at first, second and third time point of tumor evaluation (Time Frame - Maximum time frame will be 48 months):
ORR at first, second and third time point of tumor evaluation (according to clinical routine every 8 weeks) defined as the proportion of patients with having partial or complete response at first, second and third time point of tumor evaluation after initiation of study treatment using RECIST V1.1.

2. Disease control rate (DCR= CR+PR+SD) at first, second and third time point of tumor evaluation (Time Frame - Maximum time frame will be 48 months):
Disease control rate (DCR= CR+PR+SD) at first, second and third time point of tumor evaluation after initiation of study treatment (according to clinical routine every 8 weeks)

3. Duration of response (DoR) (Time Frame - Maximum time frame will be 48 months):
Duration of response (DoR), defined as the time from first documentation of OR to first documentation of PD according to RECISTV1.1 or death of any cause

4. Clinical response rate (CRR) at 4, 8, 16 and 24 weeks after initiation of study treatment (Time Frame - zp to 24 weeks):
Clinical response rate (CRR) at 4, 8, 16 and 24 weeks after initiation of study treatment defined as the proportion of patients assessed by the investigator as having at least one sign or symptom of clinical response.

5. Clinical benefit rate (CBR) (Time Frame - Maximum time frame will be 48 months):
Clinical benefit rate (CBR), defined as the percentage of patients with CR, PR or SD for at least 24 weeks [Time frame: initiation of study treatment to PD or death of any cause

6. Time to initial response (TTR) (Time Frame - Maximum time frame will be 48 months):
Time to initial response (TTR), defined as the time from initiation of study treatment to first documentation of objective response

7. Progression-free survival (PFS) (Time Frame - Maximum time frame will be 48 months):
Progression-free survival (PFS), defined as the time from initiation of study treatment until objective tumor progression or death, whichever occurs first

8. Time to treatment failure (TTF) (Time Frame - Maximum time frame will be 48 months):
Time to treatment failure (TTF), defined as the time from initiation of study treatment to discon-tinuation of treatment for any reason, including disease progression, treatment toxicity, and death

9. Change in tumor size (Time Frame - Maximum time frame will be 48 months):
Change in tumor size, defined as change of largest tumor-diameter on baseline tumor evaluation during the course of study treatment

10. Frequency of AE/SAE during study (Time Frame - Maximum time frame will be 48 months):
occurenec of AE/SAE during study

11. Patient reported outcomes (PRO) (Time Frame - Maximum time frame will be 48 months):
Patient reported outcomes (PRO): change from baseline to end of study in symptom burden and quality of life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Minimum score =0 Maximum score = 100. Higher score would mean a better outcome

Geprüfte Regime

  • Abemaciclib:
    Abemaciclib tablets 150 mg, 100 mg, 50 mg as clinical routine: 150 mg twice daily per os, in-label administration in combination with endocrine therapy (aromatase inhibitor or Fulvestrant)

Quelle: ClinicalTrials.gov


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