Parsaclisib in Newly Diagnosed Stage I-IIIC Triple Negative or HER2+ Breast Cancer (LCCC1820)
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|ClinicalTrials.gov Identifier: NCT04142554|
Recruitment Status : Withdrawn (Funding withdrawn from funding source.)
First Posted : October 29, 2019
Last Update Posted : November 3, 2020
The purpose of this research study is to find the lowest dose of the cancer drug parsaclisib that has an effect on the type of breast cancer a participant has. Researchers are looking at how Parsaclisib affects the immune system. They want to learn whether and how it helps the immune system to find cancer cells to fight them.
Parsaclisib is an oral drug that limits the effects of a protein called phosphatidylinositol 3-kinase δ (PI3K). By limiting P13K, parsaclisib can block certain cells that prevent the immune cells from working. As a result, it may help the body's immune system to fight tumors. Parsaclisib is being studied in several clinical trials to treat different types of cancers. Parsaclisib has not yet been approved by FDA for the treatment of cancer.
Studies have shown that a good way to find out how cancer acts when exposed to anti-cancer drugs is through a pre-operative window study. In this type of study, tissue and blood are collected before treatment. Then subjects receive a study drug for a few weeks before surgery. Blood is drawn during the course of treatment, and leftover tissue is collected during surgery. Comparing the tissue and blood before and after treatment shows the effects the study drug may have had on the tumor.
Research shows that cancers differ when you look at the DNA and RNA (genetic codes) that are inside a cancer cell. DNA and RNA carry genetic information that can determine traits in humans (such as eye color, height, reaction to treatment, etc.), as well as the traits of cancer cells. Depending on the genetic profile (particularly DNA and RNA) of the cancer, it may respond differently to parsaclisib. In this study, the investigators will look at the genetic profile of a participant's tumor by studying tissue and blood samples collected before and after receiving treatment.
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer Breast Neoplasms Triple Negative Breast Cancer HER2-positive Breast Cancer||Drug: Parsaclisib||Phase 1|
Surgery and Treatment:
Subjects must consent to having tissue collected for research purposes during a pre-treatment research biopsy, and scheduled surgery or end of treatment research biopsy prior to study entry. Prior to their scheduled standard of care surgery or research biopsy, subjects (n = 5 per dosing cohort) will be given oral doses of parsaclisib (10, 3.0 or 1.0 mg) once daily over 14 consecutive days. Cohorts will be enrolled sequentially by dose, where the cohort with the highest dose will be enrolled first and then the next cohort with the next highest dose will be enrolled after the enrollment of the prior cohort completes.
At each dose level it will be determined whether either a 50% increase in the intratumoral CD8+ T cells/regulatory T- cell ratio or a 50% decrease in the intratumoral percentage of regulatory T cells is observed in at least 3 subjects out of 5 at that dose level. If this criterion is met, enrollment in the next highest dose level will commence. This procedure will be repeated until either this criterion is met at the lowest dose level, or when the criterion is not satisfied in a particular dose level. In the latter case, the next highest dose level will be chosen as the "minimum effective dose". In the former case, the lowest dose level will be chosen as the minimum effective dose. The doses being administered are lower than the therapeutic dose levels of parsaclisib (i.e., 20 to 30 mg once daily) recommended for subjects with lymphoma. If the criterion is not met in the first (highest) dose level, then the investigators assume the minimum effective dose is the therapeutic dose of parsaclisib (20 mg once daily) and the study will be terminated.
Blood samples will be collected prior to parsaclisib treatment for research purposes. Subjects will undergo their standard of care surgical procedure or research biopsy within 72 hours (preferably within 24 hours) of completing drug treatment. Tissue and blood samples will be collected for correlative studies during surgery or during a research biopsy procedure. Subjects who have at least 7 days of parsaclisib treatment will be considered evaluable and may have tissue collected even if they have not completed the entire 14 day treatment regimen.
Duration of Follow Up:
Subjects will be followed post-operatively as per routine standard of care. Contraceptive use should continue for 93 days after the last dose of study drug administration. Subjects removed from study treatment for unacceptable adverse events will be followed until resolution or stabilization of the adverse event. Monitoring for AEs should continue for at least 30 days after the last dose of parsaclisib is administered. AEs related to therapy will then be followed until resolution to grade ≤1, or until the condition has stabilized with no further change expected.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Window of Opportunity Study of Parsaclisib in Subjects With Newly Diagnosed Stage I-IIIC Triple-Negative or HER2-Positive Breast Cancer|
|Estimated Study Start Date :||June 1, 2020|
|Actual Primary Completion Date :||September 7, 2020|
|Actual Study Completion Date :||September 7, 2020|
Experimental: Single Arm: Parsaclisib ( Dose De-Escalation )
Prior to their scheduled standard of care surgery or research biopsy, subjects (n = 5 per dosing cohort) will be given oral doses of parsaclisib (10, 3.0 or 1.0 mg) once daily over 14 consecutive days.
Parsaclisib tablets (1.0, 2.5 or 5 mg) are administered orally daily for up to 14 days
- Minimum effective dose of parsaclisib [ Time Frame: At time of surgery (2 weeks after start of parsaclisib) ]To determine the minimum dose of parsaclisib, administered once daily for 14 consecutive days, needed in subjects with triple-negative or human epidermal growth factor receptor 2 (HER2) positive breast cancer to result in either a 50% increase in the intratumoral cluster of differentiation 8 (CD8+) Thymus (T) cells/regulatory T cell ratio or a 50% decrease in the percentage of intratumoral regulatory T cells as measured using single cell transcriptomics and/or flow cytometry.
- Minimum dose of parsaclisib needed to decrease peripheral blood regulatory T cells [ Time Frame: At time of surgery (2 weeks after start of parsaclisib) ]To determine the minimum dose of parsaclisib, administered once daily for 14 consecutive days, in subjects with triple-negative or HER2 positive breast cancer resulting in either a 50% increase in the peripheral blood CD8+ T cells/regulatory T-cell ratio or a 50% decrease in the percentage of peripheral blood regulatory T cells as measured using single cell transcriptomics and/or flow cytometry.
- Changes in regulatory T cell signature [ Time Frame: At time of surgery (2 weeks after start of parsaclisib) ]To identify changes in the regulatory T cell signature following treatment with parsaclisib in subjects with triple-negative or HER2-positive breast cancer. A regulatory T-cell gene signature expression score is defined as the average of upper quartile normalized and log2 transformed gene expression values of all genes belonging to that gene signature was calculated for each sample. Gene expression values will be determined via RNA-sequencing. A one-sided paired t-test will be used to test for significant pre-post reductions in signature values in each subject, reflecting a decrease in the abundance of intratumoral regulatory T cells.
- Changes in Ki-67 mRNA expression [ Time Frame: At time of surgery (2 weeks after start of parsaclisib) ]To identify changes in Ki-67 messenger Ribonucleic acid (mRNA) expression following treatment with parsaclisib in subjects with triple-negative or HER2-positive breast cancer. Ki-67 expression pre versus post treatment will be assessed using the average log2 fold change in gene expression between conditions.
- Comparison of reduction in the regulatory T cell signature by dose of parsaclisib [ Time Frame: At time of surgery (2 weeks after start of parsaclisib) ]The reduction in the regulatory T cell signature by dose of parsaclisib (10 mg, 3.0 mg or 1.0 mg) will be measured as Pre and post-treatment levels of regulatory T-cell total abundance (cell count) and relative abundance (percentage of all cells), and change in relative abundance (fold change in % abundance post vs pre-treatment)
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): NCT04142554
|Principal Investigator:||Carey Lisa, MD||UNC Lineberger Comprehensive Cancer Center|