Trial Outcomes & Findings for Study Evaluating the Antitumor Activity and Safety of Niraparib as Neoadjuvant Treatment in Participants With Breast Cancer (NCT NCT03329937)

Last Updated: 2025-01-08

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

21 participants

Primary outcome timeframe

At 2 months

Results posted on

2025-01-08

Participant Flow

This was an open-label, single-arm pilot study that evaluated 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.

A total of 21 participants were enrolled in the study.

Participant milestones

Participant milestones
Measure	Niraparib 200 mg Participants received niraparib 200 milligrams (mg) orally once daily in 28-day treatment cycles. After 2 cycles, participants either underwent surgery, received additional cycles of niraparib (maximum of 6 cycles total), or received neoadjuvant chemotherapy, at physician's discretion. A breast magnetic resonance imaging (MRI) was performed at the end of cycle 2 and breast ultrasounds were performed at the end of each cycle, including any additional cycles beyond cycle 2. After completion of all neoadjuvant therapy participants proceeded to surgery, at which time pathological complete response (pCR) was assessed.
Overall Study STARTED	21
Overall Study COMPLETED	21
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Niraparib 200 mg n=21 Participants Participants received niraparib 200 milligrams (mg) orally once daily in 28-day treatment cycles. After 2 cycles, participants either underwent surgery, received additional cycles of niraparib (maximum of 6 cycles total), or received neoadjuvant chemotherapy, at physician's discretion. A breast magnetic resonance imaging (MRI) was performed at the end of cycle 2 and breast ultrasounds were performed at the end of each cycle, including any additional cycles beyond cycle 2. After completion of all neoadjuvant therapy participants proceeded to surgery, at which time pathological complete response (pCR) was assessed.
Age, Continuous	44.1 Years STANDARD_DEVIATION 14.46 • n=5 Participants
Sex: Female, Male Female	21 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race/Ethnicity, Customized Race customized · Asian	1 Participants n=5 Participants
Race/Ethnicity, Customized Race customized · Black or African American	1 Participants n=5 Participants
Race/Ethnicity, Customized Race customized · White	19 Participants n=5 Participants

PRIMARY outcome

Timeframe: At 2 months

Population: Efficacy Evaluable Population. The efficacy evaluable population consisted of all participants who completed 2 cycles of treatment.

Outcome measures

Outcome measures
Measure	Niraparib 200 mg n=21 Participants Participants received niraparib 200 milligrams (mg) orally once daily in 28-day treatment cycles. After 2 cycles, participants either underwent surgery, received additional cycles of niraparib (maximum of 6 cycles total), or received neoadjuvant chemotherapy, at physician's discretion. A breast magnetic resonance imaging (MRI) was performed at the end of cycle 2 and breast ultrasounds were performed at the end of each cycle, including any additional cycles beyond cycle 2. After completion of all neoadjuvant therapy participants proceeded to surgery, at which time pathological complete response (pCR) was assessed.
Percentage of Participants With Tumor Response Measured by Breast MRI	90.5 Percentage of participants Interval 69.6 to 98.8

SECONDARY outcome

Timeframe: Up to 1 year

Population: Efficacy Evaluable Population.

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.

Outcome measures

Outcome measures
Measure	Niraparib 200 mg n=21 Participants Participants received niraparib 200 milligrams (mg) orally once daily in 28-day treatment cycles. After 2 cycles, participants either underwent surgery, received additional cycles of niraparib (maximum of 6 cycles total), or received neoadjuvant chemotherapy, at physician's discretion. A breast magnetic resonance imaging (MRI) was performed at the end of cycle 2 and breast ultrasounds were performed at the end of each cycle, including any additional cycles beyond cycle 2. After completion of all neoadjuvant therapy participants proceeded to surgery, at which time pathological complete response (pCR) was assessed.
Percentage of Participants With Pathological Complete Response (pCR)	38.1 Percentage of participants Interval 18.1 to 61.6

SECONDARY outcome

Timeframe: Up to 6 months

Population: Efficacy Evaluable Population.

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.

Outcome measures

Outcome measures
Measure	Niraparib 200 mg n=21 Participants Participants received niraparib 200 milligrams (mg) orally once daily in 28-day treatment cycles. After 2 cycles, participants either underwent surgery, received additional cycles of niraparib (maximum of 6 cycles total), or received neoadjuvant chemotherapy, at physician's discretion. A breast magnetic resonance imaging (MRI) was performed at the end of cycle 2 and breast ultrasounds were performed at the end of each cycle, including any additional cycles beyond cycle 2. After completion of all neoadjuvant therapy participants proceeded to surgery, at which time pathological complete response (pCR) was assessed.
Percentage of Participants With Tumor Response as Measured by Breast Ultrasound	95.2 Percentage of participants Interval 76.2 to 99.9

SECONDARY outcome

Timeframe: Baseline and up to 6 months

Population: Efficacy Evaluable Population.

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.

Outcome measures

Outcome measures
Measure	Niraparib 200 mg n=21 Participants Participants received niraparib 200 milligrams (mg) orally once daily in 28-day treatment cycles. After 2 cycles, participants either underwent surgery, received additional cycles of niraparib (maximum of 6 cycles total), or received neoadjuvant chemotherapy, at physician's discretion. A breast magnetic resonance imaging (MRI) was performed at the end of cycle 2 and breast ultrasounds were performed at the end of each cycle, including any additional cycles beyond cycle 2. After completion of all neoadjuvant therapy participants proceeded to surgery, at which time pathological complete response (pCR) was assessed.
Percent Change From Baseline in Tumor Volume Measured by Ultrasound	-83.4 Percent change Standard Deviation 20.45

SECONDARY outcome

Timeframe: Baseline and at 2 months

Population: Efficacy Evaluable Population.

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.

Outcome measures

Outcome measures
Measure	Niraparib 200 mg n=21 Participants Participants received niraparib 200 milligrams (mg) orally once daily in 28-day treatment cycles. After 2 cycles, participants either underwent surgery, received additional cycles of niraparib (maximum of 6 cycles total), or received neoadjuvant chemotherapy, at physician's discretion. A breast magnetic resonance imaging (MRI) was performed at the end of cycle 2 and breast ultrasounds were performed at the end of each cycle, including any additional cycles beyond cycle 2. After completion of all neoadjuvant therapy participants proceeded to surgery, at which time pathological complete response (pCR) was assessed.
Percent Change From Baseline in Tumor Volume Measured by MRI	-77.0 Percent change Standard Deviation 25.14

SECONDARY outcome

Timeframe: Up to 1 year

Population: Safety Population. Safety Population comprised of participants who received at least one dose of study medication.

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.

Outcome measures

Outcome measures
Measure	Niraparib 200 mg n=21 Participants Participants received niraparib 200 milligrams (mg) orally once daily in 28-day treatment cycles. After 2 cycles, participants either underwent surgery, received additional cycles of niraparib (maximum of 6 cycles total), or received neoadjuvant chemotherapy, at physician's discretion. A breast magnetic resonance imaging (MRI) was performed at the end of cycle 2 and breast ultrasounds were performed at the end of each cycle, including any additional cycles beyond cycle 2. After completion of all neoadjuvant therapy participants proceeded to surgery, at which time pathological complete response (pCR) was assessed.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Treatment Discontinuations and Dose Reductions Due to Adverse Events (AEs) Any TEAE	21 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Treatment Discontinuations and Dose Reductions Due to Adverse Events (AEs) Any SAE	2 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Treatment Discontinuations and Dose Reductions Due to Adverse Events (AEs) Any TEAEs leading to nirapirib reduction	4 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Treatment Discontinuations and Dose Reductions Due to Adverse Events (AEs) Any TEAEs leading to niraparib discontinuation	0 Participants

Adverse Events

Niraparib 200 mg

Serious events: 2 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Niraparib 200 mg n=21 participants at risk Participants received niraparib 200 milligrams (mg) orally once daily in 28-day treatment cycles. After 2 cycles, participants either underwent surgery, received additional cycles of niraparib (maximum of 6 cycles total), or received neoadjuvant chemotherapy, at physician's discretion. A breast magnetic resonance imaging (MRI) was performed at the end of cycle 2 and breast ultrasounds were performed at the end of each cycle, including any additional cycles beyond cycle 2. After completion of all neoadjuvant therapy participants proceeded to surgery, at which time pathological complete response (pCR) was assessed.
Blood and lymphatic system disorders Thrombocytopenia	4.8% 1/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
Congenital, familial and genetic disorders Ventricular septal defect	4.8% 1/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.

Other adverse events

Other adverse events
Measure	Niraparib 200 mg n=21 participants at risk Participants received niraparib 200 milligrams (mg) orally once daily in 28-day treatment cycles. After 2 cycles, participants either underwent surgery, received additional cycles of niraparib (maximum of 6 cycles total), or received neoadjuvant chemotherapy, at physician's discretion. A breast magnetic resonance imaging (MRI) was performed at the end of cycle 2 and breast ultrasounds were performed at the end of each cycle, including any additional cycles beyond cycle 2. After completion of all neoadjuvant therapy participants proceeded to surgery, at which time pathological complete response (pCR) was assessed.
Gastrointestinal disorders Nausea	76.2% 16/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
Gastrointestinal disorders Constipation	19.0% 4/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
Gastrointestinal disorders Diarrhoea	14.3% 3/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
Gastrointestinal disorders Vomiting	9.5% 2/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
General disorders Fatigue	66.7% 14/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
General disorders Mucosal inflammation	9.5% 2/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
Metabolism and nutrition disorders Decreased appetite	23.8% 5/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
Metabolism and nutrition disorders Hypermagnesaemia	9.5% 2/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
Nervous system disorders Headache	19.0% 4/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
Nervous system disorders Dizziness	9.5% 2/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
Nervous system disorders Dysgeusia	9.5% 2/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
Investigations Neutrophil count decreased	14.3% 3/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
Investigations White blood cell count decreased	14.3% 3/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
Investigations Blood alkaline phosphatase increased	9.5% 2/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
Investigations Platelet count decreased	9.5% 2/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
Psychiatric disorders Insomnia	33.3% 7/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
Psychiatric disorders Anxiety	9.5% 2/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
Blood and lymphatic system disorders Anaemia	23.8% 5/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
Blood and lymphatic system disorders Neutropenia	9.5% 2/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
Blood and lymphatic system disorders Thrombocytopenia	9.5% 2/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
Vascular disorders Hot flush	23.8% 5/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
Infections and infestations Breast cellulitis	9.5% 2/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Arthralgia	9.5% 2/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Bone pain	9.5% 2/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Nasal congestion	14.3% 3/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Cough	9.5% 2/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	9.5% 2/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
Reproductive system and breast disorders Menstruation irregular	9.5% 2/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications	19.0% 4/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders	14.3% 3/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.
Ear and labyrinth disorders Ear and labyrinth disorders	9.5% 2/21 • Up to 1 year TEAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study medication.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER