Ignite Creation Date:
2024-05-06 @ 10:33 AM
Last Modification Date:
2024-10-26 @ 12:31 PM
Study NCT ID:
NCT03281902
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2023-12-13
First Post:
2017-09-07
Brief Title:
Genetic Analysis in Blood and Tumor Samples From Patients With Advanced or Metastatic Estrogen Receptor Positive and HER2 Negative Breast Cancer Receiving Palbociclib and Endocrine Therapy
Sponsor:
Mayo Clinic
Organization:
Mayo Clinic
Study Overview
Official Title:
Prospective Study to Evaluate the Role of Tumor Sequencing in Women Receiving Palbociclib for Advanced Hormone Receptor HR-Positive Breast Cancer PROMISE
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2023-12
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:
None
Brief Summary:
This research trial studies genetic profiles in blood and tumor samples from patients with estrogen receptor positive and HER2 negative breast cancer that has spread to other places in the body who are receiving palbociclib and endocrine therapy Examining the genetic changes associated with the cancer and comparing the genetic material from the cancer tissue with the genetic material found in the blood may help doctors to develop customized treatment for breast cancer
Detailed Description:
PRIMARY OBJECTIVES
I To identify novel genomic variants and pathways associated with baseline as well as the change in serum thymidine kinase TK1 levels measured pre-registration after two cycles and at disease progression among women with advanced hormone receptor HR positive breast cancer treated with palbociclib and endocrine therapy ET
SECONDARY OBJECTIVES
I To generate patient derived xenograft PDXs and organoids from tumor biopsies obtained at pre-registration at 2 months and at disease progression to test novel endocrine therapy combinations PDX Aim II To test whether PDX engraftment is associated with progression free survival PDX Aim Sequencing Aims III to describe changes in the genomic landscape of HR-positive HER2-negative advanced breast cancer by comparing sequencing data deoxyribonucleic acid DNA and ribonucleic acid RNA from preregistration archival breast primary tumors when available with tumor biopsies obtained preregistration after two months on study and at disease progression on palbociclib and ET
IV To evaluate whether genomic variants and pathways measured using DNA and RNA sequencing at pre-registration and after two months of treatment are associated with 1 PFS 2 baseline and changes in serum TK1 Sequencing Aim V To tabulate the number of patients who have targetable mutations found in the preregistration tumor biopsy and to record their subsequent treatment regimen following progression on palbociclib and ET Sequencing Aim VI To compare and contrast the actionable genomic alterations found in cfDNA or CTC derived DNA that are not found in tumor tissue Sequencing Aim VII To assess whether genetic alterations known to be associated with endocrine monotherapy resistance are seen in circulating tumor- DNA ctDNA and circulating tumor cell CTC derived DNA Sequencing Aim VIIITo determine whether use of a 3D micro cancer model combined with sequencing data from tumor biopsies ctDNA and PDXs collected at the time of disease progression can be used to personalize future treatment options for PROMISE participants Sequencing Aim IX To compare the changes in Ki67 levels by immunohistochemistry IHC and serum TK1 levels after 2 months of treatment Proliferative biomarker aim X To assess whether the change in Ki67 and serum TK1 levels after 2 months of treatment with palbociclib and ET is associated with progression free survival PFS outcomes Proliferative biomarker aim XI To assess whether high baseline serum TK1 levels 200 DuL are associated with PFS outcomes Proliferative biomarker aim XII To assess whether an increase in TK1 between 2 months and 12 months is associated with PFS Proliferative biomarker aim XIII To assess the change in EMT marker expression eg Vimentin SLUG and E-cadherin and serum TK1 after two months of treatment with palbociclib and ET EMT aim XIV To determine the association between the expression of EMT markers and Ki67 levels after two months of treatment with palbociclib and ET EMT aim XV To determine the association between the expression of EMT markers after two months of treatment with palbociclib and ET and PFS outcomes EMT aim XVI To assess whether there is a change in the level of tumor infiltrating lymphocytes TILs observed in archival tumor at pre-registration at 2 months and at disease progression on palbociclib and ET Immune aim XVII To assess the change in TILs including CD8 PD-L1 and FOXP3 after 2 months of treatment with palbociclib and ET Immune aim XVIII To assess the association between TILs and serum TK1 levels at preregistration at 2 months and at disease progression on palbociclib and ET Immune aim XIX To characterize and evaluate changes in the immune landscape of HR HER2 -MBC using serial biopsies obtained pre-registration at 2 months and at disease progression as well as archived primary tumor when available using digital spatial profiling DSP NanoString GeoMx platform Immune aim XX To assess by use of mass cytometry CyTOF whether i peripheral blood immune markers obtained pretreatment are associated with either TK1 or PFS and ii whether the changes in peripheral blood immune markers after 2 cycles of treatment are associated with changes in serum TK1 levels Immune aim XXI To discover putative mechanistic connections underlying bacteria-drug interactions in all patients Microbiome aim XXII To identify the biomolecular features within the gut stool microbiome and its association with the pharmacokinetics and pharmacodynamics of letrozole and palbociclib Microbiome aim XXIII To discover novel predictive biomarkers of resistance to CDK46i and ET andor to find biomarkers that add additional predictive power to other promising biomarkers such as TK1 by performing the following Metabolic proteomic and lipidomic aim XXIV A metabolomics analysis 5000 metabolites sampled through untargeted mass spectrometry at Metabolon of paired serum samples obtained pre-registration and after 2 months on palbociclib and ET
XXIVa An Olink-based cytokines panel Explore panel of 1536 proteins of paired serum samples obtained pre-registration and after 2 months on palbociclib and ET
XXIVb A lipidomics analysis platform TBC of paired serum samples obtained pre-registration and after 2 months on palbociclib and ET
XXV To correlate the changes in the metabolites cytokines and lipids to the preregistration genomic tumor characteristics serial Ki67 levels and PFS outcomes Metabolic proteomic and lipidomic aim XXVI To assess the change in serum TK1 levels after 2 months and at disease progression on palbociclib and ET and its association with the preregistration CD44highCD24lowERlow cancer stem cell-like phenotype including the following total and phosphorylated AURKA breast cancer stemness biomarkers CD44 CD24 ALDH1 EMT transcription factors SMAD5 SOX2 cyclin E cyclin A and phosphorylated Retinoblastoma Rb Other aim XXVII To examine shifts in the populations of epithelial like CTCs and stem cell like CTCs during the course of endocrine therapy with palbociclib Other aim XXVIII To assess CTC expression of ER HER2 and other markers of endocrine resistance Other aim
OUTLINE
Patents undergo collection of blood and stool samples at baseline 7 days after letrozole monotherapy treatment and at completion of each cycle urine samples at baseline and completion of each cycle and saliva samples at baseline Patients also undergo collection of blood and urine samples at disease progression Biopsy samples are analyzed for genetic profile via genome sequencing and ribonucleic acid RNA sequencing Biopsy samples are also used for the generation of xenograft mice model
After completion of study patients are followed up every 6 months for 7 years
I To identify novel genomic variants and pathways associated with baseline as well as the change in serum thymidine kinase TK1 levels measured pre-registration after two cycles and at disease progression among women with advanced hormone receptor HR positive breast cancer treated with palbociclib and endocrine therapy ET
SECONDARY OBJECTIVES
I To generate patient derived xenograft PDXs and organoids from tumor biopsies obtained at pre-registration at 2 months and at disease progression to test novel endocrine therapy combinations PDX Aim II To test whether PDX engraftment is associated with progression free survival PDX Aim Sequencing Aims III to describe changes in the genomic landscape of HR-positive HER2-negative advanced breast cancer by comparing sequencing data deoxyribonucleic acid DNA and ribonucleic acid RNA from preregistration archival breast primary tumors when available with tumor biopsies obtained preregistration after two months on study and at disease progression on palbociclib and ET
IV To evaluate whether genomic variants and pathways measured using DNA and RNA sequencing at pre-registration and after two months of treatment are associated with 1 PFS 2 baseline and changes in serum TK1 Sequencing Aim V To tabulate the number of patients who have targetable mutations found in the preregistration tumor biopsy and to record their subsequent treatment regimen following progression on palbociclib and ET Sequencing Aim VI To compare and contrast the actionable genomic alterations found in cfDNA or CTC derived DNA that are not found in tumor tissue Sequencing Aim VII To assess whether genetic alterations known to be associated with endocrine monotherapy resistance are seen in circulating tumor- DNA ctDNA and circulating tumor cell CTC derived DNA Sequencing Aim VIIITo determine whether use of a 3D micro cancer model combined with sequencing data from tumor biopsies ctDNA and PDXs collected at the time of disease progression can be used to personalize future treatment options for PROMISE participants Sequencing Aim IX To compare the changes in Ki67 levels by immunohistochemistry IHC and serum TK1 levels after 2 months of treatment Proliferative biomarker aim X To assess whether the change in Ki67 and serum TK1 levels after 2 months of treatment with palbociclib and ET is associated with progression free survival PFS outcomes Proliferative biomarker aim XI To assess whether high baseline serum TK1 levels 200 DuL are associated with PFS outcomes Proliferative biomarker aim XII To assess whether an increase in TK1 between 2 months and 12 months is associated with PFS Proliferative biomarker aim XIII To assess the change in EMT marker expression eg Vimentin SLUG and E-cadherin and serum TK1 after two months of treatment with palbociclib and ET EMT aim XIV To determine the association between the expression of EMT markers and Ki67 levels after two months of treatment with palbociclib and ET EMT aim XV To determine the association between the expression of EMT markers after two months of treatment with palbociclib and ET and PFS outcomes EMT aim XVI To assess whether there is a change in the level of tumor infiltrating lymphocytes TILs observed in archival tumor at pre-registration at 2 months and at disease progression on palbociclib and ET Immune aim XVII To assess the change in TILs including CD8 PD-L1 and FOXP3 after 2 months of treatment with palbociclib and ET Immune aim XVIII To assess the association between TILs and serum TK1 levels at preregistration at 2 months and at disease progression on palbociclib and ET Immune aim XIX To characterize and evaluate changes in the immune landscape of HR HER2 -MBC using serial biopsies obtained pre-registration at 2 months and at disease progression as well as archived primary tumor when available using digital spatial profiling DSP NanoString GeoMx platform Immune aim XX To assess by use of mass cytometry CyTOF whether i peripheral blood immune markers obtained pretreatment are associated with either TK1 or PFS and ii whether the changes in peripheral blood immune markers after 2 cycles of treatment are associated with changes in serum TK1 levels Immune aim XXI To discover putative mechanistic connections underlying bacteria-drug interactions in all patients Microbiome aim XXII To identify the biomolecular features within the gut stool microbiome and its association with the pharmacokinetics and pharmacodynamics of letrozole and palbociclib Microbiome aim XXIII To discover novel predictive biomarkers of resistance to CDK46i and ET andor to find biomarkers that add additional predictive power to other promising biomarkers such as TK1 by performing the following Metabolic proteomic and lipidomic aim XXIV A metabolomics analysis 5000 metabolites sampled through untargeted mass spectrometry at Metabolon of paired serum samples obtained pre-registration and after 2 months on palbociclib and ET
XXIVa An Olink-based cytokines panel Explore panel of 1536 proteins of paired serum samples obtained pre-registration and after 2 months on palbociclib and ET
XXIVb A lipidomics analysis platform TBC of paired serum samples obtained pre-registration and after 2 months on palbociclib and ET
XXV To correlate the changes in the metabolites cytokines and lipids to the preregistration genomic tumor characteristics serial Ki67 levels and PFS outcomes Metabolic proteomic and lipidomic aim XXVI To assess the change in serum TK1 levels after 2 months and at disease progression on palbociclib and ET and its association with the preregistration CD44highCD24lowERlow cancer stem cell-like phenotype including the following total and phosphorylated AURKA breast cancer stemness biomarkers CD44 CD24 ALDH1 EMT transcription factors SMAD5 SOX2 cyclin E cyclin A and phosphorylated Retinoblastoma Rb Other aim XXVII To examine shifts in the populations of epithelial like CTCs and stem cell like CTCs during the course of endocrine therapy with palbociclib Other aim XXVIII To assess CTC expression of ER HER2 and other markers of endocrine resistance Other aim
OUTLINE
Patents undergo collection of blood and stool samples at baseline 7 days after letrozole monotherapy treatment and at completion of each cycle urine samples at baseline and completion of each cycle and saliva samples at baseline Patients also undergo collection of blood and urine samples at disease progression Biopsy samples are analyzed for genetic profile via genome sequencing and ribonucleic acid RNA sequencing Biopsy samples are also used for the generation of xenograft mice model
After completion of study patients are followed up every 6 months for 7 years
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2017-01479 | REGISTRY | None | None |
| MC1634 | OTHER | None | None |
| P30CA015083 | NIH | None | None |
| P50CA168504 | NIH | None | None |
| 17-002697 | OTHER | Mayo Clinic Institutional Review Board | httpsreporternihgovquickSearchP50CA168504 |