Back to resultsThe Clinical Trial to Evaluate the Pharmacokinetics, Safety and Tolerability of ZL-2306 (Niraparib) in Patients With Ovarian Cancer
Primary Purpose
Ovarian Cancer
Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
ZL-2306 (niraparib)
Sponsored by
About this trial
This is an interventional treatment trial for Ovarian Cancer focused on measuring PARP inhibitor, BRCA mutation
Eligibility Criteria
Inclusion Criteria:
- Signed informed consent .
- Female, age ≥ 18 years.
- Histologically confirmed diagnosis of FIGO stage III or IV ovarian cancer, fallopian tube cancer, or primary peritoneal cancer.
- Has received no further than second-line platinum-based chemotherapy, and has clinical complete response (CR) or partial response (PR) at least following 4 courses of the last platinum-based chemotherapy.
- ECOG 0-1.
- Has good organ function, including:
- Patient of childbearing potential, has a negative pregnancy test when enrolled and promises to use an adequate method of contraception or abstain from activities that could result in pregnancy from enrolment to the end of study and during the 3 months after the last dose of the study treatment, or be of non-childbearing potential, can be enrolled in the study.
- Is able to adhere to the protocol.
- Has recovered from previous chemotherapy induced toxic side effects to ≤ grade 1 CTCAE or basal level, apart from ≤ grade 2 CTCAE peripheral neuropathy or hair loss symptoms at steady state.
Exclusion Criteria:
- Has a known hypersensitivity to the active or inactive ingredients of ZL-2306 (niraparib) or compound which has similar chemical structure to ZL-2306 (niraparib).
- Has symptomatic uncontrolled brain or leptomeningeal metastasis.
- Major surgery or chemotherapy within 3 weeks of starting the study or patient has not recovered from any effects of the surgery.
- Receive palliative radiotherapy encompassing > 20% of the bone marrow within 1 week of entering the study.
- Be diagnosed any invasive cancer other than ovarian cancer (apart from cured basal cell carcinoma and squamous cell carcinoma) within 2 years prior to study enrolment.
- Has a history or current diagnosis of myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML).
- Has other serious or uncontrolled disease
- Has any disease, treatment and laboratory abnormality that may interfere the study results and affect the fully attendance of study. Or the patient is considered to be not suitable for the study by the investigator. Cannot receive platelet or red blood cell transfusion within 4 weeks of study drug administration.
- Pregnant, breastfeeding or expecting to conceive children during the study treatment period.
- Corrected QT (QTc) interval > 470 msec.
- Use proton pump inhibitors, antacids or histamine 2 (H2) blockers within 48hrs prior to the first drug administration for PK measurement.
Sites / Locations
- Beijing Cancer Hospital
- Sun Yat-sen University Cancer Center
- Haerbin Medical University Cancer Hospital
- Hunan Cancer Hospital
- Fudan University Shanghai Cnacer Center
- The West China Second UniversityHospital of Sichuan University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ZL-2306 (niraparib)
Arm Description
Subjects will be randomised into 100mg, 200mg, 300mg dose group at the first day of the first cycle.
Outcomes
Primary Outcome Measures
Maximum plasma drug concentration (Cmax)
Time to reach Cmax (Tmax)
Terminal rate constant (λz)
Elimination half-life (t1/2)
Area under the plasma concentration-time curve from time zero to 24hrs (AUC (0-24))
Area under the plasma concentration-time curve from time zero to time of last measurable concentration (AUC(0-t)) and from zero to infinity (AUC0-∞)
Apparent total body clearance of the drug from plasma (CL/F)
Apparent volume of distribution (Vd/f)
Mean residence time (MRT)
Degree of fluctuation (DF)
Maximum plasma drug concentration at steady-state (Css max)
Time to reach Css max (Tss max)
Minimum plasma drug concentration at steady-state (Css min)
Area under the plasma concentration-time curve from time zero to the end of drug administration (AUCss)
Steady-state apparent total body clearance of drug from plasma (Clss/F)
Accumulation ratio following multiple drug administration (RAC)
The plasma drug concentration before drug administration
Secondary Outcome Measures
Number of participants with adverse events as assessed by CTCAE v4.0
Full Information
NCT ID
NCT03551171
First Posted
April 20, 2018
Last Updated
January 22, 2019
Sponsor
Zai Lab (Shanghai) Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT03551171
Brief Title
The Clinical Trial to Evaluate the Pharmacokinetics, Safety and Tolerability of ZL-2306 (Niraparib) in Patients With Ovarian Cancer
Official Title
An Open-Label,Single-Arm,Phase I Clinical Trial to Evaluate the Pharmacokinetics,Safety and Tolerability of ZL-2306 (Niraparib) in Patients With Ovarian Cancer,Fallopian Tube Cancer and Primary Peritoneal Cancer (Collectively Termed as Ovarian Cancer)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
December 19, 2017 (Actual)
Primary Completion Date
May 3, 2018 (Actual)
Study Completion Date
July 10, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Zai Lab (Shanghai) Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
5. Study Description
Brief Summary
Niraparib is a potent and highly selective PARP-1/-2 inhibitor. The primary objective of this trial is to evaluate the pharmacokinetic (PK) properties of ZL-2306 (niraparib) and its metabolite M1 in patients from Mainland China with ovarian cancer, following a single and multiple oral administration of the study drug at the indicated dose (300mg, 200mg or 100mg), once a day.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer
Keywords
PARP inhibitor, BRCA mutation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
42 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ZL-2306 (niraparib)
Arm Type
Experimental
Arm Description
Subjects will be randomised into 100mg, 200mg, 300mg dose group at the first day of the first cycle.
Intervention Type
Drug
Intervention Name(s)
ZL-2306 (niraparib)
Intervention Description
About 30 subjects will be enrolled to the study, and randomised into 300mg, 200mg and 100mg dose groups (about 10 subjects per group).
All subjects will be randomised into indicated dose group (300mg, 200mg or 100mg) at the first day of the first cycle. A single administration of ZL-2306 (niraparib) will be given to the subjects at indicated dose.
Primary Outcome Measure Information:
Title
Maximum plasma drug concentration (Cmax)
Time Frame
From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Title
Time to reach Cmax (Tmax)
Time Frame
From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Title
Terminal rate constant (λz)
Time Frame
From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Title
Elimination half-life (t1/2)
Time Frame
From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Title
Area under the plasma concentration-time curve from time zero to 24hrs (AUC (0-24))
Time Frame
From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Title
Area under the plasma concentration-time curve from time zero to time of last measurable concentration (AUC(0-t)) and from zero to infinity (AUC0-∞)
Time Frame
From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Title
Apparent total body clearance of the drug from plasma (CL/F)
Time Frame
From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Title
Apparent volume of distribution (Vd/f)
Time Frame
From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Title
Mean residence time (MRT)
Time Frame
From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Title
Degree of fluctuation (DF)
Time Frame
From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Title
Maximum plasma drug concentration at steady-state (Css max)
Time Frame
From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Title
Time to reach Css max (Tss max)
Time Frame
From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Title
Minimum plasma drug concentration at steady-state (Css min)
Time Frame
From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Title
Area under the plasma concentration-time curve from time zero to the end of drug administration (AUCss)
Time Frame
From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Title
Steady-state apparent total body clearance of drug from plasma (Clss/F)
Time Frame
From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Title
Accumulation ratio following multiple drug administration (RAC)
Time Frame
From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Title
The plasma drug concentration before drug administration
Time Frame
From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Secondary Outcome Measure Information:
Title
Number of participants with adverse events as assessed by CTCAE v4.0
Time Frame
From the signing of ICF till the end of this study (30 days after the last administration of the study drug or the date to close the clinical trial database, whichever is earlier)
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed informed consent .
Female, age ≥ 18 years.
Histologically confirmed diagnosis of FIGO stage III or IV ovarian cancer, fallopian tube cancer, or primary peritoneal cancer.
Has received no further than second-line platinum-based chemotherapy, and has clinical complete response (CR) or partial response (PR) at least following 4 courses of the last platinum-based chemotherapy.
ECOG 0-1.
Has good organ function, including:
Patient of childbearing potential, has a negative pregnancy test when enrolled and promises to use an adequate method of contraception or abstain from activities that could result in pregnancy from enrolment to the end of study and during the 3 months after the last dose of the study treatment, or be of non-childbearing potential, can be enrolled in the study.
Is able to adhere to the protocol.
Has recovered from previous chemotherapy induced toxic side effects to ≤ grade 1 CTCAE or basal level, apart from ≤ grade 2 CTCAE peripheral neuropathy or hair loss symptoms at steady state.
Exclusion Criteria:
Has a known hypersensitivity to the active or inactive ingredients of ZL-2306 (niraparib) or compound which has similar chemical structure to ZL-2306 (niraparib).
Has symptomatic uncontrolled brain or leptomeningeal metastasis.
Major surgery or chemotherapy within 3 weeks of starting the study or patient has not recovered from any effects of the surgery.
Receive palliative radiotherapy encompassing > 20% of the bone marrow within 1 week of entering the study.
Be diagnosed any invasive cancer other than ovarian cancer (apart from cured basal cell carcinoma and squamous cell carcinoma) within 2 years prior to study enrolment.
Has a history or current diagnosis of myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML).
Has other serious or uncontrolled disease
Has any disease, treatment and laboratory abnormality that may interfere the study results and affect the fully attendance of study. Or the patient is considered to be not suitable for the study by the investigator. Cannot receive platelet or red blood cell transfusion within 4 weeks of study drug administration.
Pregnant, breastfeeding or expecting to conceive children during the study treatment period.
Corrected QT (QTc) interval > 470 msec.
Use proton pump inhibitors, antacids or histamine 2 (H2) blockers within 48hrs prior to the first drug administration for PK measurement.
Facility Information:
Facility Name
Beijing Cancer Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100000
Country
China
Facility Name
Sun Yat-sen University Cancer Center
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510000
Country
China
Facility Name
Haerbin Medical University Cancer Hospital
City
Harbin
State/Province
Heilongjiang
ZIP/Postal Code
150000
Country
China
Facility Name
Hunan Cancer Hospital
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410013
Country
China
Facility Name
Fudan University Shanghai Cnacer Center
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200000
Country
China
Facility Name
The West China Second UniversityHospital of Sichuan University
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610000
Country
China
12. IPD Sharing Statement
Citations:
PubMed Identifier
31439812
Citation
Zhang J, Zheng H, Gao Y, Lou G, Yin R, Ji D, Li W, Wang W, Xia B, Wang D, Hou J, Yan J, Hei Y, Zhang ZY, Milton A, Wu X. Phase I Pharmacokinetic Study of Niraparib in Chinese Patients with Epithelial Ovarian Cancer. Oncologist. 2020 Jan;25(1):19-e10. doi: 10.1634/theoncologist.2019-0565. Epub 2019 Aug 22.
Results Reference
derived
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The Clinical Trial to Evaluate the Pharmacokinetics, Safety and Tolerability of ZL-2306 (Niraparib) in Patients With Ovarian Cancer
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