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

NCT03911453 | Completed Early Phase 1 DMC FDA Drug

• 2 other identifiers: 303881903397220
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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).

  Six months

Secondary Outcomes (5)

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

  Six months

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

  Six months

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

  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).

  Six months

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

  Six months

Study Arms (1)

Treatment (rucaparib)

EXPERIMENTAL

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

Interventions

Rucaparib DRUG

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).

Treatment (rucaparib)

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Arizona: lead

Study Sites (1)

University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

rucaparib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Pavani Chalasani, MD

  University of Arizona

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2019
• First Posted: April 11, 2019
• Study Start: April 19, 2019
• Primary Completion: July 16, 2021
• Study Completion: July 16, 2021
• Last Updated: October 3, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)