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

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

Tracking Information

• First Submitted Date: April 9, 2019
• First Posted Date: April 11, 2019
• Last Update Posted Date: February 17, 2021
• Actual Study Start Date: April 19, 2019
• Estimated Primary Completion Date: November 30, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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: Interventional
• Study Phase: Early Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Breast Cancer

Intervention

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

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

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 10, 2019): 16
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 30, 2021
• Estimated Primary Completion Date: November 30, 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03911453
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Responsible Party: University of Arizona
• Study Sponsor: University of Arizona
• Collaborators: Not Provided

Investigators

• Principal Investigator: Pavani Chalasani, MD; University of Arizona

• PRS Account: University of Arizona
• Verification Date: February 2021