Ignite Creation Date:
2024-05-06 @ 3:35 PM
Last Modification Date:
2024-10-26 @ 1:52 PM
Study NCT ID:
NCT04681768
Status:
RECRUITING
Last Update Posted:
2023-11-29
First Post:
2020-12-18
Brief Title:
Abemaciclib in Combination With Endocrine Therapy as First Line Therapy in Metastatic Breast Cancer Patients
Sponsor:
Technical University of Munich
Organization:
Technical University of Munich
Study Overview
Official Title:
Abemaciclib in Combination With Endocrine Therapy as First Line Therapy in Metastatic Breast Cancer Patients With Symp-tomatic Visceral Metastases or High Tumor Burden
Status:
RECRUITING
Status Verified Date:
2023-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Abemacare
Brief Summary:
Breast cancer is one of the most common cancers in women 20-30 of all breast cancer patients are faced with advanced disease comprising both locally advanced breast cancer LABC and metastatic breast cancer MBC 80 of MBC cases are diagnosed as hormone receptor HR positive disease The main systemic treatment options for these women include endocrine therapy ET The need of over-coming de novo or acquired resistance to ET in metastatic breast cancer has led to the integration of CDK46 inhibitors into combined ET of MBC Abemaciclib represents a selective and potent small molecule inhibitor of CDK46 which has been granted approval by the European Medical Association EMA In two phase III trials Abemaciclib has been shown to double treatment efficacy in terms of PFS prolongation to improve ORR and to prolong overall survival At the same time it has been shown that side effects of the drug are well manageable and QoL of patients under Abemaciclib is maintained
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 CDK46-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 ERposHER2neg breast cancer patients with symptomatic visceral metastases or high tumor burden
LDH-levels above 400 Ul 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
LDH-levels above 400 Ul 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None