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
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|ClinicalTrials.gov Identifier: NCT03281902|
Recruitment Status : Active, not recruiting
First Posted : September 13, 2017
Last Update Posted : June 18, 2021
|Condition or disease||Intervention/treatment|
|Advanced Breast Carcinoma Locally Advanced Breast Carcinoma Metastatic Breast Carcinoma Recurrent Breast Carcinoma Stage III Breast Cancer AJCC v7 Stage IIIA Breast Cancer AJCC v7 Stage IIIB Breast Cancer AJCC v7 Stage IIIC Breast Cancer AJCC v7 Stage IV Breast Cancer AJCC v6 and v7||Procedure: Biopsy Procedure: Biospecimen Collection Other: Laboratory Biomarker Analysis|
|Study Type :||Observational|
|Actual Enrollment :||68 participants|
|Official Title:||Prospective Study to Evaluate the Role of Tumor Sequencing in Women Receiving Palbociclib for Advanced Hormone Receptor (HR)-Positive, Breast Cancer (PROMISE)|
|Actual Study Start Date :||November 13, 2017|
|Estimated Primary Completion Date :||March 28, 2022|
|Estimated Study Completion Date :||December 13, 2022|
Ancillary-Correlative (genetic profile analysis)
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 RNA sequencing. Biopsy samples are also used for the generation of xenograft mice model.
Undergo tumor biopsy
Procedure: Biospecimen Collection
Undergo collection of blood, urine, stool, and saliva
Other: Laboratory Biomarker Analysis
- Bioinformatics analysis [ Time Frame: Up to 3 years ]Next-generation sequencing data will be used to identify variants associated with the progression free survival. Pathology analysis will also be performed.
- Ki67 and TK1 changes [ Time Frame: after 2 months of treatment ]Spearman rank correlation coefficients will be used to assess the relationship between tumor ki67 levels and serum TK1 levels prior to the start of treatment and after 2 months of treatment with palbocic.
- Changes in EMT markers (including Vimentin, SLUG and E-cadherin) and tumor infiltrating lymphocytes (TILs) (including CD8, PD-L1, and FOXP3) [ Time Frame: after 2 months of treatment ]Wilcoxon signed rank tests will be used to assess the fold changes in EMT and TILs after 2 cycles of treatment. Benjamini-Hochberg procedure will be used to control false postive rate.
- Changes in serum TK1 levels [ Time Frame: After 2 months of treatment ]Wilcoxon rank sum tests will be used to assess whether a given element of the CD44high/CD24/low/estrogen receptor (ER) low cancer stem cell-like phenotype differ between those whose TK1 levels fell below 200 after 2 cycles of treatment and those whose TK1 levels remained above 200 after 2 cycles of treatment.
- Change in phenotype of Ki67 and serum TK1 levels [ Time Frame: After 2 months of treatment ]The parameter estimates from fitting a univariate Cox model to these data will be used to obtain an estimate of the hazard ratio and its corresponding 95% confidence interval.
- Differences between those with and without a blood draw taken [ Time Frame: After 2 months of treatment ]A Wilcoxon rank sum test will be used to assess whether baseline TK1 levels differ among those who discontinue treatment prior to the 2 month blood draw and those who do not.
Biospecimen Retention: Samples With DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03281902
|United States, Arizona|
|Mayo Clinic in Arizona|
|Scottsdale, Arizona, United States, 85259|
|United States, Florida|
|Mayo Clinic in Florida|
|Jacksonville, Florida, United States, 32224-9980|
|United States, Minnesota|
|Mayo Clinic in Rochester|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Ciara C O'Sullivan||Mayo Clinic in Rochester|