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

NCT03329937 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 2133553000-01-005
• Study Type: interventional
• Target: 21
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Neoplasms, Breast

Keywords

Niraparib; Human epidermal growth factor receptor; Breast cancer; Breast ultrasound; Magnetic resonance imaging

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Tumor Response Measured by Breast MRI

  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 Outcomes (5)

• Percentage of Participants With Pathological Complete Response (pCR)

  Up to 1 year

• Percentage of Participants With Tumor Response as Measured by Breast Ultrasound

  Up to 6 months

• Percent Change From Baseline in Tumor Volume Measured by Ultrasound

  Baseline and up to 6 months

• Percent Change From Baseline in Tumor Volume Measured by MRI

  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)

  Up to 1 year

Study Arms (1)

Participants with HER2-negative and BRCAmut breast cancer

EXPERIMENTAL

Participants with HER2-negative and BRCAmut localized breast cancer (primary tumor \>=1 cm) will receive niraparib (200 mg PO).

Drug: Niraparib

Interventions

Niraparib DRUG

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.

Participants with HER2-negative and BRCAmut breast cancer

Eligibility Criteria

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

You may qualify if:

• 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:
• Absolute neutrophil count (ANC) \>=1500 per microliters (/μL).
• Platelets \>=100,000/μL.
• Hemoglobin \>=9 grams per deciliter (g/dL).
• Serum creatinine \<=1.5\*upper limit of normal (ULN) or calculated creatinine clearance \>=50 milliliters per minute (mL/min) using Cockcroft-Gault equation.
• 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.
• 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).

You may not qualify if:

• 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).

Sponsors & Collaborators

• Tesaro, Inc.: lead

Related Publications (1)

• Spring LM, Han H, Liu MC, Hamilton E, Irie H, Santa-Maria CA, Reeves J, Pan P, Shan M, Tang Y, Graham JR, Hazard S, Ellisen LW, Isakoff SJ. Neoadjuvant study of niraparib in patients with HER2-negative, BRCA-mutated, resectable breast cancer. Nat Cancer. 2022 Aug;3(8):927-931. doi: 10.1038/s43018-022-00400-2. Epub 2022 Jul 4.

  PMID: 35788722 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

niraparib

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: October 20, 2017
• First Posted: November 6, 2017
• Study Start: April 12, 2018
• Primary Completion: January 2, 2020
• Study Completion: March 31, 2020
• Last Updated: January 8, 2025
• Results First Posted: January 12, 2021

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.