Niraparib in Combination With Trastuzumab in Metastatic HER2+ Breast Cancer

NCT03368729 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: F2017000 (UAB 17112)
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 7

Brief Summary

The human epidermal growth factor receptor 2 (HER2) regulates cell growth and survival. Approximately 15-20% of all breast cancers are HER2-positive, which are an aggressive and fast-growing subtype of breast cancer. This study will evaluate a new treatment using a potent Poly polymerase (PARP) inhibitor known as Niraparib. Niraparib will be combined with trastuzumab, a HER2-targeted agent, to evaluate the safety and tolerability in patients with metastatic HER2 positive breast cancer. It is anticipated that the combination of drugs will improve survival and have few side effects.

Conditions

Metastatic Breast Cancer; HER2 Positive Breast Carcinoma

Keywords

metastatic breast cancer; HER2 positive; Poly (ADP-Ribose) polymerase (PARP); Niraparib; Trastuzumab

Outcome Measures

Primary Outcomes (2)

• Phase 1: Dose-limiting toxicity (DLT)

  A DLT is defined as hematological events \> or equal to grade 3 leukopenia, anemia, and thrombocytopenia and also non-hematological events \> or equal to grade 3 fatigue, nausea, constipation, vomiting, or diarrhea.

  Baseline to 6 weeks

• Phase 2: Objective Response Rate

  Response and progression of disease will be evaluated using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Committee.

  Baseline up to 100 weeks

Secondary Outcomes (3)

• Number of adverse events

  Baseline up to 100 weeks

• Progression-free survival

  Baseline to the date of first documented progression to date of death from any cause, whichever comes first, assessed up to 100 months

• Phase 1: Niraparib levels

  Baseline to 25 days

Study Arms (3)

Phase 1: Niraparib 200 mg + Trastuzumab 6 mg/kg

EXPERIMENTAL

In phase 1 patients in this first arm will receive 200 mg Niraparib in combination with 6 mg/kg Trastuzumab given IV every 3 weeks.

Drug: Niraparib; Drug: Trastuzumab

Phase 1: Niraparib 100 mg + Trastuzumab 6 mg/kg

EXPERIMENTAL

In phase 1 patients in this second arm will receive Niraparib 100 mg in combination with 6 mg/kg Trastuzumab given IV every 3 weeks.

Drug: Niraparib; Drug: Trastuzumab

Phase 2: Niraparib 200 mg or 100 mg + Trastuzumab 6 mg/kg

EXPERIMENTAL

The dosage of Niraparib in phase 2 will be determined by the response of patients in Phase 1. A dosage of Niraparib 200 mg will be given along with Trastuzumab 6 mg/kg IV unless a dose limiting toxicity occurs in Phase 1. If so, Niraparib 100 mg will be given with Trastuzumab 6 mg/kg (instead of Niraparib 200 mg).

Drug: Niraparib; Drug: Trastuzumab

Interventions

Niraparib DRUG

Niraparib is an oral PARP-1 and -2 inhibitor with high potency.

Also known as: formerly MK-4827

Phase 1: Niraparib 100 mg + Trastuzumab 6 mg/kg; Phase 1: Niraparib 200 mg + Trastuzumab 6 mg/kg; Phase 2: Niraparib 200 mg or 100 mg + Trastuzumab 6 mg/kg

Trastuzumab DRUG

Trastuzumab is a commercially available agent administered by intravenous infusion. A loading dose of 8 mg/kg will be given as the first dose followed with all subsequent doses of 6 mg/kg every 3 weeks.

Phase 1: Niraparib 100 mg + Trastuzumab 6 mg/kg; Phase 1: Niraparib 200 mg + Trastuzumab 6 mg/kg; Phase 2: Niraparib 200 mg or 100 mg + Trastuzumab 6 mg/kg

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: This study is for women only.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women age ≥ 18 years
• Eastern Cooperative Oncology Group performance status 0-2 (Karnofsky \>60%).
• Patients with metastatic breast cancer.
• HER2 (human epidermal growth factor receptor 2)-positive breast cancer prospectively determined on the primary tumor by a local pathology laboratory and defined as: Immunohistochemistry (IHC) score of 3+ and/or positive by ISH (defined by In Situ Hybridization ratio of ≥ 2.0 for the number of HER2 gene copies to the number of chromosome 17 copies). Both IHC and ISH assays will be performed; however, only one positive result is required for eligibility.
• Estrogen/progesterone receptor positive OR negative disease allowed.
• Patients must have measurable disease per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• Patients that have failed at least one anti-HER2 therapy in the metastatic setting.
• Patients must have normal organ and marrow function as defined below:
• absolute neutrophil count ≥1,500/mL
• platelets ≥100,000/mL
• total bilirubin ≤ institutional upper limit of normal (ULN)
• aspartate aminotransferase (AST)/alanine aminotransferase (ALT) 5 ≤ X institutional ULN
• creatinine ≤ institutional ULN OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
• Baseline left ventricular ejection fraction (LVEF) ≥ 50% measured by echocardiogram (preferred) or multigated acquisition (MUGA) scans.
• Willing and able to comply with the requirements of the protocol.

You may not qualify if:

• Metastatic breast cancer patients who are HER2 positive and have NOT progressed on at least one prior HER2-targeted therapies for metastatic disease
• Patients who have not recovered from CTCAE, v. 4.03 grade 2 or higher toxicities of prior therapy to the point that they would be appropriate for re-dosing will be ineligible for study treatment. Subjects receiving weekly therapy must have a washout period from prior chemotherapy of as least one week. Washout period for chemotherapy administered every 2, 3, or 4 weeks will be 2, 3, and 4 weeks respectively, provided subject has recovered from toxicities of prior therapy such that retreatment is appropriate.
• Patients must be at least two weeks from prior RT
• Patients must have a one-week washout period from prior hormonal therapy (e.g. testosterone, estrogen, progestin, gonadotropin-releasing hormone antagonist).
• Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Note: Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging \[using the identical imaging modality for each assessment, either MRI or CT scan\] for at least 4 weeks prior to the first dose of study treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and have not been using steroids for at least 7 days prior to study treatment. Carcinomatous meningitis precludes a patient from study participation regardless of clinical stability.
• No concurrent anti-cancer treatment of any type
• Patients with known germline BRCA 1 or BRCA 2 mutations
• Patient has undergone prior treatment with a known poly(ADP-ribose) polymerase (PARP) inhibitor.
• Prior treatment of a total doxorubicin \>360 mg/m2 (or equivalent)
• Patient has known active hepatitis B (eg, hepatitis B surface antigen \[HBsAg\] reactive) or hepatitis C (eg, hepatitis C virus ribonucleic acid \[HCV RNA\] \[qualitative\] is detected).
• Patient has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
• Chronic immunosuppressive therapies including systemic corticosteroids or concurrent short-term use of immunosuppressive therapies is not allowed. Short- term corticosteroid use must be discontinued at least 2 weeks prior to study treatment.
• Patients with known grade 2 or greater allergic reactions attributed to compounds of similar chemical or biological composition to niraparib are ineligible for study enrollment.
• Patients with known grade 2 or greater allergic reactions attributed to compounds of similar chemical or biological composition to herceptin are ineligible for study enrollment.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Translational Breast Cancer Research Consortium: collaborator
• Tesaro, Inc.: collaborator
• Susan G. Komen Breast Cancer Foundation: collaborator
• Breast Cancer Research Foundation of Alabama: collaborator
• The V Foundation: collaborator

Study Sites (7)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Montefiore

The Bronx, New York, 10461, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Washington-

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

niraparib; Trastuzumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Erica Stringer-Reasor, M.D.

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: There are two phases to this study. Phase 1 will enroll 6-12 patients and Phase 2 will enroll up to 40. Trastuzumab will be given intravenously at 6 mg/kg on Day 1 for each 21 day cycle in both phases. Niraparib will be given by mouth every day at a dosage of 200 mg for phase 1 participants and 200 mg (or 100 mg) for phase 2 participants. Tumor measurement and response will be monitored by MRI or CT scans after cycles 3 and 6 and then every 12 weeks for up to 2 years or until disease progression. Blood and tissue samples will be collected for pharmacokinetics, biomarkers, and laboratory evaluations.

Study Record Dates

• First Submitted: November 27, 2017
• First Posted: December 11, 2017
• Study Start: September 6, 2019
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: January 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)