Back to results

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

Primary Purpose

Breast Cancer

Status

Active

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Rucaparib

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring Breast Cancer, Triple Negative, Breast Tumors, PD-L1, PARP, PARPi, Rucaparib

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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)
Early stage breast cancer (stage I-III) and not be candidate for neoadjuvant chemotherapy
Be informed of the investigational nature of the study and all pertinent aspects of the trial
Have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Have the ability to understand and the willingness to sign a written informed consent document in accordance with institutional and federal guidelines
Be ≥ 21 years of age
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
Have adequate bone marrow function (ANC >1000, Platelets >100,000/ml, Hemoglobin >10gm/dL)
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:

Ongoing or prior treatment with a PARPi for breast cancer or other malignancies
Receiving concurrent anti-neoplastic therapy for their breast cancer or another malignancy
Known documented or suspected hypersensitivity to the components of the study drug or analogs.
Pre-existing gastrointestinal disorders or defects (like duodenal stent etc) that would, in the opinion of the investigator, interfere with absorption of rucaparib

Sites / Locations

University of Arizona Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (rucaparib)

Arm Description

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

Outcomes

Primary Outcome Measures

Measurement of expression of PD-L1 by IHC via core biopsy.

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 change in expression of Ki67 by IHC after treatment with PARPi.

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.

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.

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).

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.

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.

Full Information

NCT ID

NCT03911453

First Posted

April 9, 2019

Last Updated

May 25, 2023

Sponsor

University of Arizona

1. Study Identification

Unique Protocol Identification Number

NCT03911453

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

April 19, 2019 (Actual)

Primary Completion Date

November 30, 2024 (Anticipated)

Study Completion Date

November 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Arizona

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer

Keywords

Breast Cancer, Triple Negative, Breast Tumors, PD-L1, PARP, PARPi, Rucaparib

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment (rucaparib)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Rucaparib

Intervention Description

Primary Outcome Measure Information:

Title

Measurement of expression of PD-L1 by IHC via core biopsy.

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).

Time Frame

Six months

Secondary Outcome Measure Information:

Title

Measure change in expression of Ki67 by IHC after treatment with PARPi.

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).

Time Frame

Six months

Title

Measure and quantify change in number of tumor-infiltrating lymphocytes.

Description

Measure and quantify change in number of tumor-infiltrating lymphocytes via blood testing.

Time Frame

Six months

Title

Measure levels of tumor PARylation in pre- and post-PARPi therapy by IHC.

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.

Time Frame

Six months

Title

Measure change in expression of programmed cell death-1 with ligand (PD-L1) pre- and post-PARPi therapy in circulating tumor cells (CTCs).

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.

Time Frame

Six months

Title

Measure cfDNA mutational expression for homologous recombination deficiency (HRD) and correlate with PD-L1 expression at baseline and change overtime.

Description

Time Frame

Six months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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) Early stage breast cancer (stage I-III) and not be candidate for neoadjuvant chemotherapy Be informed of the investigational nature of the study and all pertinent aspects of the trial Have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 Have the ability to understand and the willingness to sign a written informed consent document in accordance with institutional and federal guidelines Be ≥ 21 years of age 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 Have adequate bone marrow function (ANC >1000, Platelets >100,000/ml, Hemoglobin >10gm/dL) 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: Ongoing or prior treatment with a PARPi for breast cancer or other malignancies Receiving concurrent anti-neoplastic therapy for their breast cancer or another malignancy Known documented or suspected hypersensitivity to the components of the study drug or analogs. Pre-existing gastrointestinal disorders or defects (like duodenal stent etc) that would, in the opinion of the investigator, interfere with absorption of rucaparib

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pavani Chalasani, MD

Organizational Affiliation

University of Arizona

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Arizona Cancer Center

City

Tucson

State/Province

Arizona

ZIP/Postal Code

85724

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

We'll reach out to this number within 24 hrs