A Phase I Study of Niraparib Administered Concurrently With Postoperative RT in Triple Negative Breast Cancer Patients

NCT03945721 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 19-055
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

Brief Summary

This research study involves Niraparib as a possible treatment for triple negative breast cancer.

Conditions

Triple Negative Breast Cancer; Residual Disease

Keywords

Breast Cancer; Triple Negative; Locally Advanced

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose

  The proportion of subjects tolerating each maximum dose level. The trial will be monitored using a 3+3 dose escalation method.

  10 weeks

Secondary Outcomes (4)

• Locoregional Relapse

  2 years

• Distant Relapse

  2 years

• Treatment related adverse events

  2 Years

• Breast cosmesis

  2 years

Study Arms (1)

Niraparib

EXPERIMENTAL

* Niraparib will be administered orally on a daily basis * Radiation Therapy will be administered concurrently with Niraparib

Drug: Niraparib; Radiation: Radiation Therapy

Interventions

Niraparib DRUG

Niraparib is a type of drug called a "PARP inhibitor", which blocks DNA (the genetic material of cells) damage from being repaired or may prevent damage from occurring in the first place. In cancer treatment, inhibiting PARP may help kill cancer cells by not allowing the cancer cells to repair its DNA damage or prevent DNA damage from occurring.

Niraparib

Radiation Therapy RADIATION

radiation therapy

Niraparib

Eligibility Criteria

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

You may qualify if:

• Males or Females, ≥ 18 years of age.
• Non-metastatic, histologically or cytologically-confirmed TNBC (defined as ER \<1%, PR \<1%, her-2-neu 0-1+ by IHC or FISH-negative or as per MD discretion).
• Definitive surgical treatment with breast-conserving surgery or mastectomy and axillary lymph node evaluation.
• Plans for receipt of postoperative radiation therapy to the breast/chest wall +/- regional nodes
• Residual invasive disease after NAC (any size), or at least 1.0 cm in patients who do not receive NAC and undergo surgery first.
• ECOG Performance status ≤ 1.
• Willingness to discontinue any cytotoxic chemotherapeutic agents, immunotherapy and biologic therapy at least 2 weeks prior to the start of RT.
• Adequate organ function (assessed within 30 days prior to initiation of protocol treatment, unless otherwise indicated) as follows:
• Hematology
• Absolute Neutrophil Count (ANC) ≥1500/mm3
• Platelet Count ≥100,000/mm3
• Hemoglobin ≥9.0 g/dL
• Renal Function
• Creatinine Serum ≤ 1.5 mg/dL or
• Creatinine Clearance ≥ 45 mL/mina

You may not qualify if:

• Gross residual tumor or positive margins after surgery that is un-excised (excluding positive margins at the chest wall or skin where no additional breast tissue can be removed).
• pT1aN0 or pT1bN0 (primary tumor size \<1.0 cm) triple negative breast cancer patients who do undergo neoadjuvant chemotherapy and receive surgery followed by +/- adjuvant chemotherapy.
• Receipt of PARP inhibitor at any time prior to study enrollment.
• Pregnant or expecting to conceive within the projected duration of the trial, starting with screening visit through 180 days after the last dose of trial treatment.
• Prior history of radiation therapy to the ipsilateral breast and/or regional nodes is not allowed (prior RT to other sites that was completed ≥ 1 week prior to Day 1 of protocol therapy, or if prior RT encompassed \>20% of the bone marrow it was completed ≥ 2 weeks prior to Day 1 of protocol therapy, is permitted).
• Major surgery ≤ 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to niraparib, or its components or excipients.
• Concomitant anti-neoplastic treatment is not allowed during protocol treatment and should be completed at least 2 weeks prior to commencement of protocol treatment, with resolution of associated acute toxicities. Bisphosphonates are permitted without restriction even during protocol treatment.
• Significant comorbidity: Patients with clinically significant and uncontrolled major disease or disorder that could exacerbate potential toxicities, confound safety assessments, require excluded therapy for management, or limit study compliance.
• Treatment with investigational therapy within ≤ 4 weeks, or within a time interval less than at least five half-lives of the investigational agent, whichever is shorter, prior to initiating protocol therapy. Patients may not be simultaneously enrolled in any interventional clinical trial.
• Unresolved toxicity from other agents. Patients with unresolved CTCAE v5 Grade 2 or greater toxicity, with the exception of alopecia and anemia, from prior administration of another investigational drug and/or anti-cancer treatment are not eligible.
• Known grade 3 or 4 anemia, neutropenia, or thrombocytopenia that persisted \> 4 weeks and was related to the most recent chemotherapy treatment.
• Participant must not have received a transfusion (platelets or red blood cells) ≤ 4 weeks prior to initiating protocol therapy.
• Participant must not have received colony-stimulating factors (e.g. granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 4 weeks prior to initiating protocol therapy.
• Prior malignancy within 5 years of study enrollment.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Tesaro, Inc.: collaborator

Study Sites (2)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute/Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Neoplasm, Residual; Breast Neoplasms

Interventions

niraparib; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Alice Ho, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 29, 2019
• First Posted: May 10, 2019
• Study Start: July 11, 2019
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028
• Last Updated: September 29, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: BCH - Contact the Technology \& Innovation Development Office at www.childrensinnovations.org or email TIDO@childrens.harvard.edu BIDMC - Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu BWH - Contact the Partners Innovations team at http://www.partners.org/innovation DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu MGH - Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (2)