Parsaclisib in Newly Diagnosed Stage I-IIIC Triple Negative or HER2+ Breast Cancer

NCT04142554 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: LCCC1820
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Breast Cancer; Breast Neoplasms; Triple Negative Breast Cancer; HER2-positive Breast Cancer

Keywords

breast; triple negative; HER2-positive; parsaclisib

Outcome Measures

Primary Outcomes (1)

• Minimum effective dose 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.

  At time of surgery (2 weeks after start of parsaclisib)

Secondary Outcomes (4)

• Minimum dose of parsaclisib needed to decrease peripheral blood regulatory T cells

  At time of surgery (2 weeks after start of parsaclisib)

• Changes in regulatory T cell signature

  At time of surgery (2 weeks after start of parsaclisib)

• Changes in Ki-67 mRNA expression

  At time of surgery (2 weeks after start of parsaclisib)

• Comparison of reduction in the regulatory T cell signature by dose of parsaclisib

  At time of surgery (2 weeks after start of parsaclisib)

Study Arms (1)

Single Arm: Parsaclisib ( Dose De-Escalation )

EXPERIMENTAL

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.

Drug: Parsaclisib

Interventions

Parsaclisib DRUG

Parsaclisib tablets (1.0, 2.5 or 5 mg) are administered orally daily for up to 14 days

Single Arm: Parsaclisib ( Dose De-Escalation )

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is able to understand and give written informed consent for removal of at least 2 cores of tissue via a pre-treatment research biopsy. Is able to understand and give written informed consent for either collection of leftover tissue at time of surgery and via an end of treatment (EOT) research biopsy).
• Is ≥ 18 years of age.
• Has histologically confirmed newly diagnosed Stage I-IIIC invasive breast cancer that is triple negative (ER/PR \<1%, HER2 negative) or HER2-positive, and meets the criteria listed below:
• a. HER 2 positive or overexpressed HER2 confirmed by immunohistochemistry (IHC), and florescence in situ hybridization (ISH) according to the 2018 ASCO-CAP guideline: i. IHC score of 3+ without ISH HER2/CEP17 OR ii. ISH HER2/CEP17 amplified with ratio higher than 2.0 OR if reported average HER2 copy number ≥ 6 signals/cell b. Scheduled for lumpectomy, mastectomy or neoadjuvant chemotherapy as first treatment for cancer c. No prior or current therapy for breast cancer d. Amenable to a baseline research breast biopsy e. Amenable to a post-therapy research biopsy (for patients going on to neoadjuvant chemotherapy and not straight to surgery). For patients going directly to surgery, post-therapy biopsy will be obtained at the time of surgery.
• Must have sufficient time to receive at least 7 consecutive days of parsaclisib therapy prior to definitive surgery or initiation of chemotherapy..
• Has an ECOG performance status ≤ 1.
• Is able to swallow and retain oral medication.
• Demonstrates adequate organ function as defined below; all screening labs to be obtained within 72 hr of initiating study treatment.
• Hemoglobin (Hgb) - ≥ 10.0 g/dL
• Absolute Neutrophil Count (ANC) - ≥ 1.5 × 109/L
• Absolute Lymphocyte Count (ALC) - \>500 cells/μL
• Platelets - ≥ 100 × 109/L
• Creatinine - ≤1.5 × ULN OR Calculated creatinine clearance - ≥ 60 mL/min for subject with creatinine levels \> 1.5 × ULN (creatinine should be calculated per institutional standard)
• Bilirubin - ≤ 1.5 × ULN or direct bilirubin ≤ ULN for subject with total bilirubin \>1.5 × ULN
• Aspartate aminotransferase (AST) - ≤ 2.5 × ULN

You may not qualify if:

• Prior history of another known malignancy other than breast cancer within the previous 2 years with the exception of adequately treated basal cell carcinoma or cervical intraepithelial neoplasia, cervical carcinoma in situ or melanoma in situ.
• Is pregnant or lactating.
• Has a concomitant medical condition that precludes adequate study treatment compliance or assessment, such as bleeding disorders or any other medical condition that would increase risks of additional core biopsy for biomarkers.
• Use of any potent CYP3A4 inhibitors or inducers (e.g., grapefruit or grapefruit juice) within 14 days or 5 half-lives (whichever is longer) before the first dose of parsaclisib.
• Has allergy to inactive components of the study medication.
• History of autoimmune disease or irritable bowel syndrome (IBS), or active colitis.
• Inability to take oral medications (e.g., impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of oral medications such as ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
• Is participating in another therapeutic clinical trial or has received another investigational agent within 30 days prior to informed consent.
• Known Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (with the exception of chronic or cleared HBV and HCV infection which is allowed).
• Has acute or currently active/requiring anti-viral therapy, hepatic or biliary disease (with the exception of subjects with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment).
• Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
• Medical history of a disease that requires ongoing steroid therapy for \>14 days.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• Incyte Corporation: collaborator

Related Links

• University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

parsaclisib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Carey Lisa, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2019
• First Posted: October 29, 2019
• Study Start: June 1, 2020
• Primary Completion: September 7, 2020
• Study Completion: September 7, 2020
• Last Updated: November 3, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share