Clinical Trials /

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

NCT03911453

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

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

  • Breast Cancer

Interventions

DrugSynonymsArms
RucaparibTreatment (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

NameTypeDescriptionInterventions
Treatment (rucaparib)ExperimentalPatients 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
  • Rucaparib

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

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