Description:
This is a single arm window of opportunity trial conducted in patients with early stage
triple negative breast tumors to evaluate if treatment with a Poly(ADP-ribose) polymerase
(PARP) inhibitor will increase expression of programmed cell death-1 with ligand (PD-L1) in
triple negative breast tumors.
Title
- Brief Title: Window of Opportunity Trial, PARP Inhibitor Rucaparib Affect on PD-L1 Expression in Triple Negative Breast Tumors
- Official Title: Window of Opportunity Trial to Evaluate Change in PD-L1 Expression in Triple Negative Breast Tumors in Response to the PARP Inhibitor Rucaparib
Clinical Trial IDs
- ORG STUDY ID:
30388
- SECONDARY ID:
1903397220
- NCT ID:
NCT03911453
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Rucaparib | | Treatment (rucaparib) |
Purpose
This is a single arm window of opportunity trial conducted in patients with early stage
triple negative breast tumors to evaluate if treatment with a Poly(ADP-ribose) polymerase
(PARP) inhibitor will increase expression of programmed cell death-1 with ligand (PD-L1) in
triple negative breast tumors.
Detailed Description
This is a single arm window of opportunity trial conducted in patients with early stage
triple negative breast tumors. Patients who are planning to undergo surgery as part of their
initial treatment will be eligible for this study. They will be treated with single agent
rucaparib for 3 weeks and then proceed to surgery. Core-biopsies obtained at the time of
diagnosis and tumor from the surgical resection will be assessed for change in expression of
PD-L1 by Immunohistochemical assay (IHC).
Trial Arms
Name | Type | Description | Interventions |
---|
Treatment (rucaparib) | Experimental | Patients will be treated with single agent rucaparib for 3wks and then proceed to surgery. Core-biopsies (at the time of diagnosis) and tumor from the surgical resection will be assessed for change in expression of programmed cell death-1 with ligand (PD-L1) by immunohistochemistry (IHC)
. Starting Dose 600 mg twice daily Dose Level -1 500 mg twice daily Dose Level -2 400 mg twice daily Dose Level -3 300 mg twice daily | |
Eligibility Criteria
Inclusion Criteria:
1. Have histologically documented triple negative breast cancer (TNBC) (defined as ER
expression ≤10% by IHC, progesterone receptor (PR) expression≤10% by IHC and HER2 0 or
1+ by IHC or Fluorescence in situ hybridization (FISH) ratio <2 or human epidermal
growth factor receptor 2 (HER2) gene copy number of <6)
2. Early stage breast cancer (stage I-III) and not be candidate for neoadjuvant
chemotherapy
3. Be informed of the investigational nature of the study and all pertinent aspects of
the trial
4. Have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
5. Have the ability to understand and the willingness to sign a written informed consent
document in accordance with institutional and federal guidelines
6. Be ≥ 21 years of age
7. Have serum creatinine < 1.5 x institutional upper limit of normal (IULN) or a
calculated creatinine clearance ≥ 30ml/min (calculated by Cockcroft Gault equation),
bilirubin ≤ 2.0, and an serum glutamic oxaloacetic transaminase (SGOT)/s erum glutamic
pyruvic transaminase (SGPT)/alkaline phosphatase ≤ 2.0 x IULN
8. Have adequate bone marrow function (ANC >1000, Platelets >100,000/ml, Hemoglobin
>10gm/dL)
9. Women of childbearing potential or male patients of reproductive potential with female
partners of childbearing potential must not consider getting pregnant and must avoid
pregnancy during the study and for at least 6 months after the last dose of rucaparib.
Female and male patients of reproductive potential must practice highly effective
methods of contraception with their partners, if of reproductive potential, during
treatment and for 6 months following last dose of rucaparib
Exclusion Criteria:
1. Ongoing or prior treatment with a PARPi for breast cancer or other malignancies
2. Receiving concurrent anti-neoplastic therapy for their breast cancer or another
malignancy
3. Known documented or suspected hypersensitivity to the components of the study drug or
analogs.
4. Pre-existing gastrointestinal disorders or defects (like duodenal stent etc) that
would, in the opinion of the investigator, interfere with absorption of rucaparib
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 21 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Measurement of expression of PD-L1 by IHC via core biopsy. |
Time Frame: | Six months |
Safety Issue: | |
Description: | To evaluate change in expression of programmed cell death-1 with ligand (PD-L1) by Immunohistochemistry (IHC) of tissue sample via core biopsy after treatment with single agent PARPi (rucaparib). |
Secondary Outcome Measures
Measure: | Measure change in expression of Ki67 by IHC after treatment with PARPi. |
Time Frame: | Six months |
Safety Issue: | |
Description: | Measure change in expression of Ki67 by immunohistochemistry of tissue sample via core biopsy after treatment with single agent Poly(ADP-ribose) polymerase inhibitor (PARPi) (rucaparib). |
Measure: | Measure and quantify change in number of tumor-infiltrating lymphocytes. |
Time Frame: | Six months |
Safety Issue: | |
Description: | Measure and quantify change in number of tumor-infiltrating lymphocytes via blood testing. |
Measure: | Measure levels of tumor PARylation in pre- and post-PARPi therapy by IHC. |
Time Frame: | Six months |
Safety Issue: | |
Description: | Measure levels of tumor PARylation (the addition of poly-ADP-ribose polymers) in pre- and post-PARPi therapy by immunohistochemistry of tissue sample via core biopsy. |
Measure: | Measure change in expression of programmed cell death-1 with ligand (PD-L1) pre- and post-PARPi therapy in circulating tumor cells (CTCs). |
Time Frame: | Six months |
Safety Issue: | |
Description: | Measure change in expression of programmed cell death-1 with ligand (PD-L1) pre- and post-PARPi therapy in circulating tumor cells (CTCs) via blood/plasma collection. |
Measure: | Measure cfDNA mutational expression for homologous recombination deficiency (HRD) and correlate with PD-L1 expression at baseline and change overtime. |
Time Frame: | Six months |
Safety Issue: | |
Description: | Measure circulating free DNA (cfDNA) mutational expression for homologous recombination deficiency (HRD) and correlate with PD-L1 expression at baseline and change overtime via blood/plasma collection. |
Details
Phase: | Early Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | University of Arizona |
Trial Keywords
- Breast Cancer
- Triple Negative
- Breast Tumors
- PD-L1
- PARP
- PARPi
- Rucaparib
Last Updated
February 17, 2021