Study Evaluating the Antitumor Activity and Safety of Niraparib as Neoadjuvant Treatment in Participants With Breast Cancer

December 20, 2024 updated by: Tesaro, Inc.

An Open-Label, Single-arm Pilot Study Evaluating the Antitumor Activity and Safety of Niraparib as Neoadjuvant Treatment in Localized, HER2-negative, BRCA-mutant Breast Cancer Patients

This is an open-label, single-arm pilot study evaluating the antitumor activity and safety of niraparib as neoadjuvant therapy in participants with Human epidermal growth factor receptor 2 (HER2)-negative and breast cancer susceptibility gene mutant (BRCAmut) localized breast cancer (primary tumor >=1 centimeters [cm]). Breast magnetic resonance imaging (MRI), breast ultrasound, and tumor core biopsy will be performed at the screening (Days -28 to -1). Participants will receive niraparib (200 milligrams [mg] orally [PO]) treatment daily for 28 days (Cycle 1) and then will undergo breast ultrasound at the end of Cycle 1 on Day 28. Based on breast ultrasound reports, the participants will either discontinue the study (disease progression) or will continue niraparib treatment (complete response [CR], partial response [PR] or stable disease [SD]) for an additional cycle (Cycle 2). A breast MRI and breast ultrasound will be performed at the end of Cycle 2. Approximately 21 participants will be enrolled in this study and the study duration will be approximately 2 years.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
21

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Fort Myers, Florida, United States, 33908
        • GSK Investigational Site
      • Tampa, Florida, United States, 33612
        • GSK Investigational Site
    • Maryland
      • Baltimore, Maryland, United States, 21231
        • GSK Investigational Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • GSK Investigational Site
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • GSK Investigational Site
    • New York
      • New York, New York, United States, 10029
        • GSK Investigational Site
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • GSK Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Participants age >= 18 years old.
  • Participants with a deleterious or suspected deleterious breast cancer susceptibility gene 1 (BRCA1) or BRCA2 mutation (germline or somatic) may be enrolled into the study based on either local or central laboratory testing of BRCA status.
  • Histologically-confirmed HER2-negative localized breast cancer by core biopsy.
  • Primary operable, non-metastatic invasive carcinoma of the breast, confirmed histologically by core biopsy. Fine-needle aspiration is not sufficient. Incisional biopsy is not allowed. In participants with multifocal and/or multicentric, the largest lesion should be measured. Both unilateral and bilateral breast cancer are allowed.
  • Primary tumor size >=1cm.
  • Measurable disease by breast ultrasound and MRI.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

  • Adequate organ function defined as:

    1. Absolute neutrophil count (ANC) >=1500 per microliters (/μL).
    2. Platelets >=100,000/μL.
    3. Hemoglobin >=9 grams per deciliter (g/dL).
    4. Serum creatinine <=1.5*upper limit of normal (ULN) or calculated creatinine clearance >=50 milliliters per minute (mL/min) using Cockcroft-Gault equation.
    5. Total bilirubin <=1.5*ULN except in participants with Gilbert's syndrome. Participants with Gilbert's syndrome may enroll if direct bilirubin <=1.5*ULN of the direct bilirubin.
    6. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <=2.5*ULN.
  • Participants must have recovered to Grade 1 toxicity from prior cancer therapy (a participant with Grade 2 neuropathy or Grade 2 alopecia is an exception to this criterion and may qualify for this study).
  • Participant able to take oral medications.

  • Participant meets the following criteria:

    1. Female participant (of childbearing potential) is not breastfeeding, has a negative serum pregnancy test within 72 hours prior to taking study drug, and agrees to abstain from activities that could result in pregnancy from Screening through 180 days after the last dose of study drug, or is of non-childbearing potential.
    2. Female participant is of non-childbearing potential (other than medical reasons) as defined:

    i) >=45 years of age and has not had menses for >1 year. ii) Amenorrheic for <2 years without a hysterectomy and oophorectomy and a follicle-stimulating hormone value in the postmenopausal range upon the screening evaluation.

iii) Has undergone post hysterectomy, bilateral oophorectomy, or tubal ligation. Documented hysterectomy, oophorectomy or tubal ligation must be confirmed in the medical records, otherwise the participant must be willing to use 2 adequate barrier methods throughout the study starting from the screening visit through 180 days after the last dose of study drug. Information must be captured appropriately within the site's source documents.

c) Male participant agrees to use an effective method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

  • Able to understand the study procedures and agree to participate in the study by providing written informed consent.

Exclusion Criteria:

  • Prior anti-cancer therapies for current malignancy.
  • Known evidence of distant metastasis. Staging studies are not required. The decision to pursue staging studies is at the discretion of the treating clinician, based on the participant's clinical and pathological findings consistent with standard guidelines.
  • Known hypersensitivity to the components of niraparib components or their formulation excipients.
  • Major surgery within 3 weeks of starting the study or participant has not recovered from any effects of any major surgery.
  • Poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, uncontrolled hypertension, active uncontrolled coagulopathy, bleeding disorder, or any psychiatric disorder that prohibits obtaining informed consent.
  • History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study drug, or is not in the best interest of the participant to participate.
  • Participant is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study drug or within the 180-day period after the last dose of study drug.
  • Immunocompromised participants.
  • Known active hepatic disease (Hepatitis B or C).
  • Prior treatment with a known PARP inhibitor.
  • Other active malignancy that warrants systemic therapy.
  • Known history of myelodysplastic syndromes (MDS) or Acute myeloid leukemia (AML).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Participants with HER2-negative and BRCAmut breast cancer
Participants with HER2-negative and BRCAmut localized breast cancer (primary tumor >=1 cm) will receive niraparib (200 mg PO).
Drug: Niraparib
Niraparib is a potent, orally active, highly selective poly adenosine diphosphate ([ADP]-ribose) polymerase 1 (PARP1) and PARP2 inhibitor. It will be supplied as 100 mg capsules and will be administered at starting dose of 200 mg PO daily throughout 28 days for 2 cycles (each cycle is 28 days), with the potential for an additional 4 cycles (maximum total of 6 cycles) at the assigned dose and schedule.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Tumor Response Measured by Breast MRI
Time Frame: At 2 months
Tumor response measured by breast MRI is defined as >=30 percent (%) reduction of tumor volume from Baseline based on primary lesion after niraparib treatment without any new lesion development. Tumor volume was calculated as (length × width × height × pi [π])/6. Responses were assessed as Clinical complete response (CR): A complete disappearance of all tumor signs in the breast as assessed by imaging test. Clinical partial response (PR): A reduction in the tumor volume of the primary tumor size by >=30% assessed by palpation or imaging test. Clinical stable disease (SD): No significant change in tumor volume during treatment. Clinical progressive disease (cPD): The development of new, previously undetected lesions, or an estimated increase in the size of the primary lesion by greater than 20%. Percentage of participants with tumor response and its 95 percent confidence interval (CI) has been presented. The 95% CI was the binomial exact CI based on Clopper-Pearson method.
At 2 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Pathological Complete Response (pCR)
Time Frame: Up to 1 year
pCR is defined as ypT0/Tis ypN0 by receipt of pre-operative chemotherapy (Yes versus No). Following neoadjuvant therapy, pathological staging is recorded using the 'yp' designation. ypT0/Tis ypN0 is the absence of invasive cancer in the breast and axillary nodes. pCR is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0/Tis ypN0 in the current American Joint Committee on Cancer [AJCC] staging system). Percentage of participants with pCR rate its 95 percent CI has been presented. CI was based on binomial exact CI.
Up to 1 year
Percentage of Participants With Tumor Response as Measured by Breast Ultrasound
Time Frame: Up to 6 months
Tumor response rate was based on the change in tumor volume as measured by breast ultrasound; a response was considered >=30 percent reduction of tumor volume from Baseline without any new lesion development. Tumor volume was calculated as (length × width × height × π)/6. Percentage of participants with tumor response and its 95 percent CI has been presented. CI was based on binomial exact CI.
Up to 6 months
Percent Change From Baseline in Tumor Volume Measured by Ultrasound
Time Frame: Baseline and up to 6 months
Percentage change in tumor volume from Baseline was measured using ultrasound. Baseline was defined as the most recent measurement prior to the first administration of niraparib. Tumor volume was calculated as (length × width × height × π)/6. The percentage reduction in tumor volume was set as 99% if the tumor becomes too small to measure at the post-baseline visit. Percent change from Baseline was defined as greatest change in volume, derived from all available cycles of niraparib (range from cycle 2 to 6) and multiplied by 100.
Baseline and up to 6 months
Percent Change From Baseline in Tumor Volume Measured by MRI
Time Frame: Baseline and at 2 months
Percentage change in tumor volume from Baseline after 2 months of niraparib treatment was measured using MRI. Baseline was defined as the most recent measurement prior to the first administration of niraparib. Tumor volume was calculated as (length × width × height × π)/6. The percentage reduction in tumor volume was set as 99% if the tumor becomes too small to measure at the post-baseline visit. Percent change from Baseline was defined as value of post Baseline minus Baseline value and multiplied by 100.
Baseline and at 2 months
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Treatment Discontinuations and Dose Reductions Due to Adverse Events (AEs)
Time Frame: Up to 1 year
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or an important medical event. A TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment.
Up to 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Tesaro, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: GSK Clinical Trials, GlaxoSmithKline

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 12, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 2, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 31, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 20, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 30, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 6, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 20, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 213355
  • 3000-01-005 (Other Identifier: Tesaro)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

GSK will assess requests from qualified researchers for anonymized individual patient-level data (IPD) and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About_GSK_Patient_Level_Data_Sharing_Final_13July2023.pdf

IPD Sharing Time Frame

Anonymized IPD is made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.

IPD Sharing Access Criteria

Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Neoplasms, Breast

Clinical Trials on Niraparib

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings