The Clinical Trial to Evaluate the Pharmacokinetics, Safety and Tolerability of ZL-2306 (Niraparib) in Patients With Ovarian Cancer

• ClinicalTrials.gov Identifier: NCT03551171
• Recruitment Status: Completed
• First Posted: June 11, 2018
• Last Update Posted: January 24, 2019
• Sponsor: Zai Lab (Shanghai) Co., Ltd.
• Information provided by (Responsible Party): Zai Lab (Hong Kong), Ltd. ( Zai Lab (Shanghai) Co., Ltd. )

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.

Condition or disease	Intervention/treatment	Phase
Ovarian Cancer	Drug: ZL-2306 (niraparib)	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 42 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: December 19, 2017
• Actual Primary Completion Date: May 3, 2018
• Actual Study Completion Date: July 10, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: ZL-2306 (niraparib); Subjects will be randomised into 100mg, 200mg, 300mg dose group at the first day of the first cycle.	Drug: ZL-2306 (niraparib); 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.

Outcome Measures

Primary Outcome Measures :

1. Maximum plasma drug concentration (Cmax) [ Time Frame: From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days) ]
2. Time to reach Cmax (Tmax) [ Time Frame: From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days) ]
3. Terminal rate constant (λz) [ Time Frame: From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days) ]
4. Elimination half-life (t1/2) [ Time Frame: From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days) ]
5. 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) ]
6. 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) ]
7. 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) ]
8. Apparent volume of distribution (Vd/f) [ Time Frame: From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days) ]
9. Mean residence time (MRT) [ Time Frame: From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days) ]
10. Degree of fluctuation (DF) [ Time Frame: From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days) ]
11. 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) ]
12. Time to reach Css max (Tss max) [ Time Frame: From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days) ]
13. 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) ]
14. 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) ]
15. 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) ]
16. Accumulation ratio following multiple drug administration (RAC) [ Time Frame: From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days) ]
17. 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 Measures :

1. 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) ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Signed informed consent .
2. Female, age ≥ 18 years.
3. Histologically confirmed diagnosis of FIGO stage III or IV ovarian cancer, fallopian tube cancer, or primary peritoneal cancer.
4. 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.
5. ECOG 0-1.
6. Has good organ function, including:
7. 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.
8. Is able to adhere to the protocol.
9. 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:

1. 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).
2. Has symptomatic uncontrolled brain or leptomeningeal metastasis.
3. Major surgery or chemotherapy within 3 weeks of starting the study or patient has not recovered from any effects of the surgery.
4. Receive palliative radiotherapy encompassing > 20% of the bone marrow within 1 week of entering the study.
5. 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.
6. Has a history or current diagnosis of myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML).
7. Has other serious or uncontrolled disease
8. 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.
9. Pregnant, breastfeeding or expecting to conceive children during the study treatment period.
10. Corrected QT (QTc) interval > 470 msec.
11. Use proton pump inhibitors, antacids or histamine 2 (H2) blockers within 48hrs prior to the first drug administration for PK measurement.

Contacts and Locations

Locations

China, Beijing

Beijing Cancer Hospital

Beijing, Beijing, China, 100000

China, Guangdong

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China, 510000

China, Heilongjiang

Haerbin Medical University Cancer Hospital

Harbin, Heilongjiang, China, 150000

China, Hunan

Hunan Cancer Hospital

Changsha, Hunan, China, 410013

China, Shanghai

Fudan University Shanghai Cnacer Center

Shanghai, Shanghai, China, 200000

China, Sichuan

The West China Second UniversityHospital of Sichuan University

Chengdu, Sichuan, China, 610000

Sponsors and Collaborators

Zai Lab (Shanghai) Co., Ltd.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Zai Lab (Shanghai) Co., Ltd.
• ClinicalTrials.gov Identifier: NCT03551171
• Other Study ID Numbers: ZL-2306-002
• First Posted: June 11, 2018
• Last Update Posted: January 24, 2019
• Last Verified: May 2018

• 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

Keywords provided by Zai Lab (Hong Kong), Ltd. ( Zai Lab (Shanghai) Co., Ltd. ):

PARP inhibitor; BRCA mutation

Additional relevant MeSH terms:

Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Endocrine System Diseases; Gonadal Disorders; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Niraparib; Poly(ADP-ribose) Polymerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents