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Window of Opportunity Trial, PARP Inhibitor Rucaparib Affect on PD-L1 Expression in Triple Negative Breast Tumors

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ClinicalTrials.gov Identifier: NCT03911453
Recruitment Status : Recruiting
First Posted : April 11, 2019
Last Update Posted : February 17, 2021
Sponsor:
Information provided by (Responsible Party):
University of Arizona

Tracking Information
First Submitted Date  ICMJE April 9, 2019
First Posted Date  ICMJE April 11, 2019
Last Update Posted Date February 17, 2021
Actual Study Start Date  ICMJE April 19, 2019
Estimated Primary Completion Date November 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 10, 2019)
Measurement of expression of PD-L1 by IHC via core biopsy. [ Time Frame: Six months ]
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).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 10, 2019)
  • Measure change in expression of Ki67 by IHC after treatment with PARPi. [ Time Frame: Six months ]
    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 and quantify change in number of tumor-infiltrating lymphocytes. [ Time Frame: Six months ]
    Measure and quantify change in number of tumor-infiltrating lymphocytes via blood testing.
  • Measure levels of tumor PARylation in pre- and post-PARPi therapy by IHC. [ Time Frame: Six months ]
    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 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 ]
    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 cfDNA mutational expression for homologous recombination deficiency (HRD) and correlate with PD-L1 expression at baseline and change overtime. [ Time Frame: Six months ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Window of Opportunity Trial, PARP Inhibitor Rucaparib Affect on PD-L1 Expression in Triple Negative Breast Tumors
Official Title  ICMJE Window of Opportunity Trial to Evaluate Change in PD-L1 Expression in Triple Negative Breast Tumors in Response to the PARP Inhibitor Rucaparib
Brief Summary 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).
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE Drug: Rucaparib
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 PD-L1 by Immunohistochemical assay (IHC).
Study Arms  ICMJE Experimental: Treatment (rucaparib)

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

Intervention: Drug: Rucaparib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 10, 2019)
16
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 30, 2021
Estimated Primary Completion Date November 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Amy Selegue, BA, BSN, RN 520.626.0301 aselegue@email.arizona.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03911453
Other Study ID Numbers  ICMJE 30388
1903397220 ( Other Identifier: University of Arizona Cancer Center )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Arizona
Study Sponsor  ICMJE University of Arizona
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Pavani Chalasani, MD University of Arizona
PRS Account University of Arizona
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP