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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03497429
• Date of registration: 05/04/2018
• Prospective Registration: Yes
• Primary sponsor: Takeda
• Public title: A Study of Niraparib as Single Agent in Patients With Advanced Solid Tumors
• Scientific title: A Phase 1, Open-label Study of Niraparib as Single Agent in Patients With Advanced Solid Tumors
• Date of first enrolment: April 5, 2018
• Target sample size: 9
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03497429
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Sequential Assignment. Primary purpose: Other. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Japan

Contacts

• Name: Study Director
• Affiliation: Takeda

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Japanese male or female participants aged 20 years or older on the day of signing
informed consent.

2. Participants must have a cytologically- or histologically-confirmed metastatic or
locally advanced solid tumor and have failed or progressed after standard therapy, or
for which standard therapy does not exist in the opinion of the investigator.

3. Participants must have Performance Status of =<1 on the Eastern Cooperative Oncology
Group (ECOG) Performance Status Scale.

4. Participants must have adequate organ function as indicated by the following
laboratory values:

1. Hematology

- Absolute neutrophil count: >=1500/µL

- Platelet count: >=100,000/µL

- Hemoglobin: >=9 g/dL

2. Kidney

- Serum creatinine: =<1.5 × institutional upper limit of normal (ULN), OR
creatinine clearance of >=50 mL/min (as calculated using the Cockcroft Gault
equation or measured using 24-hour urine creatinine clearance) for participants
with creatinine levels >=1.5 × institutional ULN.

3. Liver

- Total bilirubin in serum: =<1.5 × ULN (except in patients with Gilbert's
syndrome). Patients with Gilbert's syndrome may be enrolled if the
participant's direct bilirubin is =<1.5 ×ULN of the direct bilirubin.

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT): =<2.5 ×
ULN OR =<5 × ULN if participants have liver metastases.

4. Coagulation (does not pertain to participants receiving anticoagulants)

- Prothrombin time (PT): =<1.2 × ULN

- Activated partial thromboplastin time (aPTT): =<1.2 × ULN

5. Female participants who:

- Are postmenopausal for at least 1 year before the screening visit, OR

- Are surgically sterile, OR

- If they are of childbearing potential, agree to practice one highly effective
method of contraception and one additional effective (barrier) method at the same
time, from the time of signing the informed consent through 180 days after the
last dose of study drug, OR

- Agree to practice true abstinence, when this is in line with the preferred and
usual lifestyle of the participant. (Periodic abstinence [eg, calendar,
ovulation, symptothermal, postovulation methods], condoms only, withdrawal,
spermicides only, and lactational amenorrhea are not acceptable methods of
contraception. Female and male condoms should not be used together.)

Male participants, even if surgically sterilized (ie, vasectomy), who:

- Agree to practice effective barrier contraception during the entire study
treatment period and through 120 days after the last dose of study drug. If the
female partner of a male participant is of child bearing potential, it should
also be advised to use a highly effective method of contraception, OR

- Agree to practice true abstinence, when this is in line with the preferred and
usual lifestyle of the participant. (Periodic abstinence [eg, calendar,
ovulation, symptothermal, postovulation methods for the female partner], condoms
only, withdrawal, spermicides only, and lactational amenorrhea are not acceptable
methods of contraception. Female and male condoms should not be used together.)

6. Voluntary written consent must be given before performance of any study related
procedure not part of standard medical care, with the understanding that consent may
be withdrawn by the patient at any time without prejudice to future medical care.

Exclusion Criteria:

1. Participant who have received chemotherapy, radiotherapy, hormonal or biological
therapy within 14 days (within 28 days for anticancer monoclonal antibody, within 42
days for nitrosoureas or mitomycin C) prior to Cycle 1 Day 1. If the participant has
residual toxicity from prior chemotherapy treatment, such toxicity must be = (NOTE: patients with Grade 2 alopecia may qualify for this study). If bevacizumab had
been used in the past, all bevacizumab-related toxicities must have resolved. Patients
with prostate cancer may have been treated with luteinizing hormone-releasing hormone
(LH-RH) analogs.

2. Participants who received a known or putative poly (ADP-ribose) polymerase (PARP)
inhibitor or other drugs that may inhibit the PARP, either as part of a clinical trial
or as standard of care.

3. Participants who initiated bisphosphonate therapy or are adjusting bisphosphonate
dose/regimen within 30 days prior to Cycle 1 Day 1. Participants on a stable
bisphosphonate regimen are eligible and may continue the treatment.

4. Treatment with any investigational products within 28 days or 5 half-lives (whichever
was longer) before Cycle 1 Day 1.

5. Participants who have symptomatic ascites or a symptomatic pleural effusion. A
participant who is treated and clinically stable for these conditions is eligible.

6. Patients with a known primary central nervous system (CNS) tumor.

7. Patients with known CNS metastases and/or carcinomatous meningitis are excluded.
However, patients with CNS metastases who have completed a course of therapy would be
eligible for the study provided they are clinically stable for 30 days prior to Cycle
1 Day 1 defined as: (1) no evidence of new or enlarging CNS metastases, (2) off
steroids, or (3) on a stable dose and administration of steroids.

8. Participants who have a hypersensitivity to the components of the study drugs or their
analogs.

9. Participants who are considered to be at high medical risk due to a serious,
uncontrolled disease, non-malignant systemic disease or active, uncontrolled
infection. Examples include, but are not limited to, uncontrolled ventricular
arrhythmia, recent (within 90 days prior to Cycle 1 Day 1) myocardial infarction,
uncontrolled major seizure disorder, unstable spinal cord compression, superior vena
cava syndrome, uncontrolled hypertension, or any psychiatric disorder that prohibits
obtaining informed consent.

10. Participants who have a history or current evidence of any condition, therapy, or lab
abnormality that might confound the results of the study, interfere with the patient's
participation throughout the study period, or study participation is not in the best
interest of the participant.

11. Known gastrointestinal (GI) disease or GI surgery that could inter


Age minimum: 20 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Advanced Solid Tumors

Intervention(s)

Drug: Niraparib

Primary Outcome(s)

Number of Participants with TEAEs leading to Treatment Discontinuation [Time Frame: Up to 28 days after the last dose (Approximately 13 months)]

Number of Participants with Treatment-Emergent Adverse Events (TEAEs) [Time Frame: Up to 28 days after the last dose (Approximately 13 months)]

Number of Participants with a Dose Limiting Toxicity (DLT) during Cycle 1 [Time Frame: Up to pre-dose of Cycle 2 Day 1 (Day 22)]

Number of Participants with Serious TEAEs [Time Frame: Up to 28 days after the last dose (Approximately 13 months)]

Number of Participants with Grade 3 or Higher TEAEs [Time Frame: Up to 28 days after the last dose (Approximately 13 months)]

Secondary Outcome(s)

AUC24:Area under the Plasma Concentration-Time Curve from Time 0 to Time 24 for Niraparib [Time Frame: Day 1 pre-dose and at multiple time points after first dose (up to Day 22)]

Tmax: Time to Reach the Maximum Plasma Concentration for Niraparib [Time Frame: Day 1 pre-dose and at multiple time points after first dose (up to Day 22)]

Cmax: Maximum Observed Plasma Concentration for Niraparib [Time Frame: Day 1 pre-dose and at multiple time points after first dose (up to Day 22)]

Secondary ID(s)

JapicCTI-183911

Niraparib-1001

U1111-1209-0340

Source(s) of Monetary Support

Please refer to primary and secondary sponsors