NCT03497429

A Study of Niraparib as Single Agent in Participants With Advanced Solid Tumors

Completed Phase 1 Results posted Last updated 9 November 2021

What this trial tests

Phase 1 trial testing Niraparib in Advanced Solid Tumors in 9 participants. Completed in 10 February 2020.

Timeline

5 April 2018

Primary endpoint
10 February 2020

10 February 2020

Quick facts

Lead sponsor	Takeda
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	sequential
Masking	none
Primary purpose	other
Enrollment	9
Start date	5 April 2018
Primary completion	10 February 2020
Estimated completion	10 February 2020
Sites	1 location across Japan

Drugs / interventions tested

• Niraparib (niraparib) — full drug profile →

Conditions studied

• Advanced Solid Tumors — all drugs for Advanced Solid Tumors →

Sponsor

Takeda — full company profile →

Who can join

20 and older, any sex, with Advanced Solid Tumors. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Dose Limiting Toxicities (DLTs) Primary · Baseline up to Day 21 in Cycle 1 (Cycle length=21 days)

DLT was evaluated as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), v4.03 and defined as any of the following events occurring during Cycle 1 that were considered by investigator to be related with niraparib: Any Grade 5 or 4 hematologic toxicity, except Grade 4 neutropenia less than (\<) 7 days; Grade 3 or 4 neutropenia with fever greater than (\>) 38.5 degree Celsius and/or infection requiring antibiotic/anti-fungal treatment; Any Grade 3, 4,or 5 non-hematologic toxicity except: Grade 3 nausea, vomiting, diarrhea/dehydration occurring in setting of

Group	Value	95% CI
Cohort 1: Niraparib 200 mg	0
Cohort 2: Niraparib 300 mg	1

Number of Participants With Treatment-emergent Adverse Events (TEAEs) Primary · From the first dose of the study drug up to 28 days after the last dose of the study drug (up to Cycle 22 Day 49) (Cycle length =21 days)

Group	Value	95% CI
Cohort 1: Niraparib 200 mg	3
Cohort 2: Niraparib 300 mg	6

Number of Participants With Grade 3 or Higher TEAEs Primary · From the first dose of the study drug up to 28 days after the last dose of the study drug (up to Cycle 22 Day 49) (Cycle length =21 days)

TEAEs were graded as per the NCI-CTCAE version 4.03. As per the NCI-CTCAE, Grade 1 (mild, asymptomatic or mild symptoms); Grade 2 (moderate, minimal, local or noninvasive intervention indicated); Grade 3 (severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated); Grade 4 (life-threatening consequences, urgent intervention indicated); Grade 5 (death related to adverse event \[AE\]).

Group	Value	95% CI
Cohort 1: Niraparib 200 mg	1
Cohort 2: Niraparib 300 mg	6

Number of Participants With Serious TEAEs Primary · From the first dose of the study drug up to 28 days after the last dose of the study drug (up to Cycle 22 Day 49) (Cycle length =21 days)

Group	Value	95% CI
Cohort 1: Niraparib 200 mg	0
Cohort 2: Niraparib 300 mg	1

Number of Participants Who Discontinued Study Drug Due to TEAEs Primary · From the first dose of the study drug up to 28 days after the last dose of the study drug (up to Cycle 22 Day 49) (Cycle length =21 days)

Group	Value	95% CI
Cohort 1: Niraparib 200 mg	0
Cohort 2: Niraparib 300 mg	2

Cmax: Maximum Observed Plasma Concentration for Niraparib Secondary · Cycle 1 Days 1 and 21: pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length =21 days)

Cycle 1 Day 1

Group	Value	95% CI
Cohort 1: Niraparib 200 mg	442.9	± 195.09
Cohort 2: Niraparib 300 mg	529.6	± 149.22

Cycle 1 Day 21

Group	Value	95% CI
Cohort 1: Niraparib 200 mg	729.2	± 387.50
Cohort 2: Niraparib 300 mg	1167	± 194.94

Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Niraparib Secondary · Cycle 1 Days 1 and 21: pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length =21 days)

Cycle 1 Day 1

Group	Value	95% CI
Cohort 1: Niraparib 200 mg	4.000	1.52 – 4.07
Cohort 2: Niraparib 300 mg	4.035	2.05 – 10.2

Cycle 1 Day 21

Group	Value	95% CI
Cohort 1: Niraparib 200 mg	3.950	3.83 – 4.03
Cohort 2: Niraparib 300 mg	2.890	2.88 – 6.00

AUC24：Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours for Niraparib Secondary · Cycle 1 Days 1 and 21: pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length =21 days)

Cycle 1 Day 1

Group	Value	95% CI
Cohort 1: Niraparib 200 mg	4931	± 2905.0
Cohort 2: Niraparib 300 mg	6270	± 2631.2

Cycle 1 Day 21

Group	Value	95% CI
Cohort 1: Niraparib 200 mg	13040	± 6493.3
Cohort 2: Niraparib 300 mg	19540	± 3117.2

Adverse events — posted to ClinicalTrials.gov

Time frame: Treatment-emergent adverse events were adverse events that started from the first dose of the study drug up to 28 days after the last dose of the study drug (up to Cycle 22 Day 49) (Cycle length =21 days). Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1: Niraparib 200 mg

Serious: 0/3 (0%)

Deaths: 0/3

Cohort 2: Niraparib 300 mg

Serious: 1/6 (17%)

Deaths: 0/6

Serious adverse events (1 terms)

Reaction	System	Cohort 1: Niraparib 200 mg	Cohort 2: Niraparib 300 mg
Pyelonephritis	Infections and infestations	—	—

Other adverse events (46 terms — click to expand)

Reaction	System	Cohort 1: Niraparib 200 mg	Cohort 2: Niraparib 300 mg
Platelet count decreased	Investigations	—	—
Aspartate aminotransferase increased	Investigations	—	—
Nausea	Gastrointestinal disorders	—	—
Blood alkaline phosphatase increased	Investigations	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Alanine aminotransferase increased	Investigations	—	—
Gamma-glutamyltransferase increased	Investigations	—	—
Vomiting	Gastrointestinal disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Fatigue	General disorders	—	—
Malaise	General disorders	—	—
Chest pain	General disorders	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Hypertension	Vascular disorders	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—
Leukopenia	Blood and lymphatic system disorders	—	—
Neutropenia	Blood and lymphatic system disorders	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—
Stomatitis	Gastrointestinal disorders	—	—
Oedema peripheral	General disorders	—	—
Pyrexia	General disorders	—	—
Pharyngitis	Infections and infestations	—	—
Fall	Injury, poisoning and procedural complications	—	—
Skin wound	Injury, poisoning and procedural complications	—	—
Blood creatinine increased	Investigations	—	—
White blood cell count decreased	Investigations	—	—
Electrocardiogram QT prolonged	Investigations	—	—
Neutrophil count decreased	Investigations	—	—
Weight decreased	Investigations	—	—
Diabetes mellitus	Metabolism and nutrition disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Dizziness	Nervous system disorders	—	—
Hallucination	Psychiatric disorders	—	—
Proteinuria	Renal and urinary disorders	—	—
Dysphonia	Respiratory, thoracic and mediastinal disorders	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—

Most-reported serious reactions: Pyelonephritis.

Data from ClinicalTrials.gov NCT03497429 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of Niraparib in Japanese participants with advanced solid tumors.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. DNA Repair Pathways in Cancer Therapy and Resistance.
   Li LY, Guan YD, Chen XS, Yang JM, et al · · 2020 · cited 254× · PMID 33628188 · DOI 10.3389/fphar.2020.629266
2. The Prognostic and Therapeutic Potential of DNA Damage Repair Pathway Alterations and Homologous Recombination Deficiency in Lung Cancer.
   Khaddour K, Felipe Fernandez M, Khabibov M, Garifullin A, et al · · 2022 · cited 7× · PMID 36358724 · DOI 10.3390/cancers14215305