Ignite Creation Date:
2024-05-06 @ 10:59 AM
Last Modification Date:
2024-10-26 @ 12:38 PM
Study NCT ID:
NCT03401359
Status:
UNKNOWN
Last Update Posted:
2018-01-17
First Post:
2017-12-11
Brief Title:
The Resistance and Immune Response to Palbociclib in Breast Cancer
Sponsor:
Samsung Medical Center
Organization:
Samsung Medical Center
Study Overview
Official Title:
Prospective Longitudinal Biomarker Study of Acquired Resistance and Immune Response to Palbociclib in Breast Cancer
Status:
UNKNOWN
Status Verified Date:
2018-01
Last Known Status:
RECRUITING
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:
None
Brief Summary:
The investigators propose to conduct a biomarker and molecular profiling study in longitudinally paired tumor biopsies and serum from patients with Hormone Receptor positive HR metastatic Breast Cancer BC treated with Palbociclib in combination with endocrine therapies
Detailed Description:
The investigators propose to conduct a biomarker and molecular profiling study in longitudinally paired tumor biopsies and serum from patients with Hormone Receptor positive HR metastatic Breast Cancer BC treated with PalbociclibPalbo in combination with endocrine therapies
The investigators plan to obtain tumor biopsy and blood samples taken at both pre-treatment and post-progression from 40 patients who develop acquired resistance to Palbo endocrine combination treatment All assays will be conducted in parallel on both pre and post-treatment samples to identify differences that may account for acquired resistance Cyclin E1 and E2 levels will be assessed by IHC on tumor biopsies Neuregulin-1 levels will be assessed by ELISA assay on serum Tumor biopsies will be further profiled using whole-exome sequencing WES and whole-transcriptome sequencing RNA-Seq Matched blood samples will be subject to WES to facilitate somatic mutation detection Paired tumor biopsies will undergo immunohistochemistry IHC analysis of TIL markers to assess Palbo-induced changes Finally we will apply the in-house circulating tumor DNA ctDNA assay which employs a custom-designed panel for studying Palbo acquired resistance towards the analysis of 40 pairs of plasma samples The custom ctDNA panel will be extended to include additional mutations identified from this study that confer acquired resistance
To further evaluate the effects of Palbo treatment on intratumoral TILs the investigators plan to acquire paired tumor biopsy and matched blood samples at baseline and two time points 6 weeks 12 weeks during the course of Palbo treatment from 20 patients And they will select metastatic BC patients who exhibit stable diseases SD in response to Palbo for tumor biopsies prior to knowledge of whether post-progression biopsy would be available Tumor biopsies will be subject to WES RNA-Seq and IHC analyses Further the investigators plan to quantify the abundance of immune cell sub-populations in the matched blood samples using flow cytometry FACS to assess Palbo treatment effects on systematic immunity
While on-treatment samples can be collected after 6 weeks and 12 weeks of initiating Palbo treatment it takes about 18 months on average for initially treated patients with late stage HR breast cancers to develop acquired resistance Only an estimated 40 of relapsed cases will have successful biopsies due to a lack of consent or difficult-to-operate biopsies such as bone-only metastases Hence the investigators plan to bank pre-treatment biopsies and blood samples from about 100 patients by Q2 2018 in order to collect 40 post-progression biopsies as matched pairs within the 2-year time frame FFPE slides will be made from all tumor biopsies including the 100 cases at baseline and subject to HE staining The investigators will detect and quantify TILs through machine learning and digital imaging analysis of the HE data
The investigators plan to obtain tumor biopsy and blood samples taken at both pre-treatment and post-progression from 40 patients who develop acquired resistance to Palbo endocrine combination treatment All assays will be conducted in parallel on both pre and post-treatment samples to identify differences that may account for acquired resistance Cyclin E1 and E2 levels will be assessed by IHC on tumor biopsies Neuregulin-1 levels will be assessed by ELISA assay on serum Tumor biopsies will be further profiled using whole-exome sequencing WES and whole-transcriptome sequencing RNA-Seq Matched blood samples will be subject to WES to facilitate somatic mutation detection Paired tumor biopsies will undergo immunohistochemistry IHC analysis of TIL markers to assess Palbo-induced changes Finally we will apply the in-house circulating tumor DNA ctDNA assay which employs a custom-designed panel for studying Palbo acquired resistance towards the analysis of 40 pairs of plasma samples The custom ctDNA panel will be extended to include additional mutations identified from this study that confer acquired resistance
To further evaluate the effects of Palbo treatment on intratumoral TILs the investigators plan to acquire paired tumor biopsy and matched blood samples at baseline and two time points 6 weeks 12 weeks during the course of Palbo treatment from 20 patients And they will select metastatic BC patients who exhibit stable diseases SD in response to Palbo for tumor biopsies prior to knowledge of whether post-progression biopsy would be available Tumor biopsies will be subject to WES RNA-Seq and IHC analyses Further the investigators plan to quantify the abundance of immune cell sub-populations in the matched blood samples using flow cytometry FACS to assess Palbo treatment effects on systematic immunity
While on-treatment samples can be collected after 6 weeks and 12 weeks of initiating Palbo treatment it takes about 18 months on average for initially treated patients with late stage HR breast cancers to develop acquired resistance Only an estimated 40 of relapsed cases will have successful biopsies due to a lack of consent or difficult-to-operate biopsies such as bone-only metastases Hence the investigators plan to bank pre-treatment biopsies and blood samples from about 100 patients by Q2 2018 in order to collect 40 post-progression biopsies as matched pairs within the 2-year time frame FFPE slides will be made from all tumor biopsies including the 100 cases at baseline and subject to HE staining The investigators will detect and quantify TILs through machine learning and digital imaging analysis of the HE data
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?:
False
Is an FDA AA801 Violation?:
None