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Trial record 11 of 48 for:    rucaparib

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 : June 6, 2019
Sponsor:
Information provided by (Responsible Party):
University of Arizona

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Rucaparib Early Phase 1

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 19, 2019
Estimated Primary Completion Date : November 30, 2019
Estimated Study Completion Date : May 30, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Rucaparib

Arm Intervention/treatment
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

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).




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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).

  2. 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.

  3. 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.

  4. 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.

  5. 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.



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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

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): NCT03911453


Contacts
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Contact: Amy Selegue, BA, BSN, RN 520.626.0301 aselegue@email.arizona.edu

Locations
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United States, Arizona
University of Arizona Cancer Center Recruiting
Tucson, Arizona, United States, 85724
Contact: Amy Selegue, BA, BSN, RN    520-626-0301    aselegue@email.arizona.edu   
Sponsors and Collaborators
University of Arizona
Investigators
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Principal Investigator: Pavani Chalasani, MD University of Arizona

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Responsible Party: University of Arizona
ClinicalTrials.gov Identifier: NCT03911453     History of Changes
Other Study ID Numbers: 30388
1903397220 ( Other Identifier: University of Arizona Cancer Center )
First Posted: April 11, 2019    Key Record Dates
Last Update Posted: June 6, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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

Keywords provided by University of Arizona:
Breast Cancer
Triple Negative
Breast Tumors
PD-L1
PARP
PARPi
Rucaparib

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Rucaparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents