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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Advanced Solid Malignancies

Intervention / Treatment
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* Drug: Fluzoparib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluzoparib<br>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<br>* Fluzoparib either at 10,20,40,80,120mg ....., capsule oral.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PARP, Advanced Solid Malignancies, Fluzoparib, Ovarian Cancer, BRCA