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

Ovarian Cancer Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03551171
• Other study ID #: ZL-2306-002
• Status: Completed
• Phase: Phase 1
• Start date: December 19, 2017
• Est. completion date: July 10, 2018

Study information

• Verified date: May 2018
• Source: Zai Lab (Shanghai) Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: July 10, 2018
• Est. primary completion date: May 3, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neoplasms, Glandular and Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

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.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing
China	Hunan Cancer Hospital	Changsha	Hunan
China	The West China Second UniversityHospital of Sichuan University	Chengdu	Sichuan
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	Haerbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	Fudan University Shanghai Cnacer Center	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Zai Lab (Shanghai) Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum plasma drug concentration (Cmax)		From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Primary	Time to reach Cmax (Tmax)		From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Primary	Terminal rate constant (?z)		From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Primary	Elimination half-life (t1/2)		From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Primary	Area under the plasma concentration-time curve from time zero to 24hrs (AUC (0-24))		From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Primary	Area under the plasma concentration-time curve from time zero to time of last measurable concentration (AUC(0-t)) and from zero to infinity (AUC0-8)		From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Primary	Apparent total body clearance of the drug from plasma (CL/F)		From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Primary	Apparent volume of distribution (Vd/f)		From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Primary	Mean residence time (MRT)		From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Primary	Degree of fluctuation (DF)		From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Primary	Maximum plasma drug concentration at steady-state (Css max)		From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Primary	Time to reach Css max (Tss max)		From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Primary	Minimum plasma drug concentration at steady-state (Css min)		From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Primary	Area under the plasma concentration-time curve from time zero to the end of drug administration (AUCss)		From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Primary	Steady-state apparent total body clearance of drug from plasma (Clss/F)		From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Primary	Accumulation ratio following multiple drug administration (RAC)		From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Primary	The plasma drug concentration before drug administration		From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Secondary	Number of participants with adverse events as assessed by CTCAE v4.0		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)