A Phase I Study of Fluzoparib in Patient With Advanced Solid Malignancies

A Phase I, Open-label, Dose Escalation Study to Assess the Safety and Tolerability of Fluzoparib Following Single and Multiple Oral Doses in Patients With Advanced Solid Malignancies

Fluzoparib is an oral potent, selective PARP-1 and PARP-2 inhibitor. The objective of this study will be to investigate the safety and tolerability of Fluzoparib Capsule when given orally to Chinese patients with advanced solid malignancies. In addition, the pharmacokinetic profile, MTD (if possible) and efficacy of Fluzoparib will be investigated.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Malignancies
• Intervention / Treatment: Drug: Fluzoparib

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital
    • Beijing, Beijing, China, 100039
      • No.307 Hospital, Academy of Military Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ECOG performance status of 0 to 1.
• Life expectancy of more than 12 weeks.
• At least one measurable lesion exists.(RECIST 1.1).
• Subjects diagnosed with advanced solid malignancies who are refractory to standard therapies or for which no standard therapy exists.
• Subjects who have overall good overall general condition.
• Signed informed consent.

Exclusion Criteria:

• Subjects who received any previous treatment with a PARP inhibitor.
• Less than 4 weeks from the last clinical trial.
• Less than 4 weeks from the last radiotherapy, chemotherapy, surgery, hermone treatment and target therapy.
• Subjects that are unable to swallow, or dysfunction of gastrointestinal absorption.
• Subjects with symptomatic uncontrolled brain metastases.
• Subjects with uncontrolled hypokalemia and hypomagnesemia before study entry.
• Subjects with a known hypersensitivity to Fluzoparib or any of the excipients of the product.
• Ongoing infection (determined by investigator).
• History of immunodeficiency, including HIV-positive, suffering from other acquired, congenital immunodeficiency disease, or history of organ transplantation.
• Subjects who can not interrupt the using of the drugs that may cause QT prolongation during study.
• Subjects had any heart disease, including: (1) angina; (2) requiring medication or clinically significant arrhythmia; (3) myocardial infarction; (4) heart failure; (5) Any heart diseases judged by investigator as unsuitable to participate in the trial.
• Female patients who are pregnancy, lactation or women who are of childbearing potential tested positive in baseline pregnancy test.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Fluzoparib; Each subject will receive a single dose of fluzoparib on day 1, and then subject will receive fluzoparib twice daily for 28 days during cycle 1.	Drug: Fluzoparib; Fluzoparib either at 10,20,40,80,120mg ....., capsule oral.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The maximum-tolerated dose (MTD) will be defined as the maximum dose level at which no more than one subject out of three experiences has a dose-limiting toxicity (DLT) upon completing one treatment cycle.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of pharmacokinetic parameter of Fluzoparib: Cmax		4 weeks
Evaluation of pharmacokinetic parameter of Fluzoparib: Tmax		4 weeks
Evaluation of pharmacokinetic parameter of Fluzoparib: t1/2		4 weeks
Evaluation of pharmacokinetic parameter of Fluzoparib: AUC		4 weeks
Preliminary antitumor activity for the regimen, objective response rate(ORR)	To evaluate ORR 8 weeks after the initiation of Fluzoparib	8 weeks
Number of participants with adverse events.	Number of Participants with treatment related Adverse Events as Assessed by CTCAE v4.0	8 weeks

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Collaborators: 307 Hospital of PLA; Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (ACTUAL): June 1, 2018
• Study Completion (ACTUAL): June 1, 2018

Study Registration Dates

• First Submitted: October 8, 2015
• First Submitted That Met QC Criteria: October 14, 2015
• First Posted (ESTIMATE): October 15, 2015

Study Record Updates

• Last Update Posted (ACTUAL): June 17, 2019
• Last Update Submitted That Met QC Criteria: June 13, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Advanced Solid Malignancies; Ovarian Cancer; PARP; Fluzoparib; BRCA
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: HR-FZPL-I-AST-TOL/PK