A Study of SC10914 in Patients With Advanced Solid Tumors
- Registration Number
- NCT02940132
- Lead Sponsor
- Jiangxi Qingfeng Pharmaceutical Co. Ltd.
- Brief Summary
SC10914 is a potent selective PARP-1 and PARP-2 inhibitor. This study aims to determine the safety , tolerability , pharmacokinetic/pharmacodynamics profile of increasing doses of SC10914 when administered orally to patients with advanced solid tumors. Furthermore, the safety and efficacy of SC10914 in patients with advanced solid tumors and negative expression of ATM or BRCA1 or BRCA2 mutation will be evaluated in expanded cohorts to establish the Recommended Phase 2 Dose(RP2D).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 72
- Signed written informed consent
- Aged 18-70 years
- Dose escalation study: Subjects diagnosed with advanced solid malignancies who are refractory to standard therapies or for which no standard therapy exists/Dose Expansion study: Subjects diagnosed with advanced solid malignancies who are refractory to standard therapies or for which no standard therapy exists and negative expression of ATM or BRCA1 or BRCA2 mutation
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- Have measurable lesion exists(RECIST 1.1)
- Life expectancy≥3 months
- Have adequate bone marrow, hepatic and renal functions
- Allergic constitution or hypersensitivity to investigational drugs or relevant drug
- Patients who received any previous treatment with a PARP inhibitor
- Patients accepted anti-cancer therapy including chemotherapy, radiotherapy, endocrinotherapy, immunotherapy, Chinese herbal treatment or other investigational drugs within 4 weeks prior to trial entry (or a longer period depending on the defined characteristics of the drugs used eg,. 6 weeks for mitomycin C or nitrosourea)
- With serious pre-existing medical conditions, such as significant cardiovascular disease and psychogenic disorders
- With family history of long QT syndrome or QTc ≥ 450 ms
- With persistent CTCAE ≧grade 2 toxicities (excluding alopecia) caused by prior medication
- With symptomatic brain metastases
- Pregnancy or lactation
- With Hepatitis B or C or human immunodeficiency virus infections
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description SC10914 SC10914 SC10914 Dose Escalation： Dose Level 1：30mg(QD) Dose Level 2：60mg(QD) Dose Level 3：120mg(QD) Dose Level 4：200mg(QD) Dose Level 5：100mg(BID) Dose Level 6：300mg(QD) Dose Level 7：150mg(BID) Dose Level 8：400mg(QD) Dose Level 9：200mg(BID) Dose Expansion： Receiving SC10914 in one of three dosage regimens(low, middle or high dose-level and QD or BID) based on the assessment of dose escalation study.
- Primary Outcome Measures
Name Time Method Dose Escalation Study: Maximum-tolerated Dose (MTD) of SC10914 30 days In dose escalation study, SC10914 will be administered to patients with advanced solid tumors. MTD is defined as the maximum dose level at which no more than one subject out of three experiences has a dose-limiting toxicity (DLT) within 30 days after accepting SC10914.
Dose Expansion Study: Recommended Phase II Dose(RP2D) of SC10914 8 weeks In dose expansion study,SC10914 will be administered to patients with advanced solid tumors and negative expression of ATM or BRCA1 or BRCA2 mutation.RP2D will be defined based on all available safety, pharmacokinetics(PK), pharmacodynamics(PD), and efficacy data collected after the start of SC10914 treatment.
- Secondary Outcome Measures
Name Time Method Evaluation of the antitumor effects of SC10914 as measured by disease control rate (DCR) 8 weeks Number of participants with treatment-related adverse events (AEs) as assessed by NCI-CTCAE v4.03 8 weeks Area under the concentration-time curve (AUC) 4 weeks Time to reach maximum concentration (Tmax) 4 weeks Maximum Concentration (Cmax) 4 weeks Trough Concentration (Ctrough) 4 weeks Elimination Half-Life (T½) 4 weeks Clearance (CL) 4 weeks Volume of Distribution (Vd) 4 weeks Evaluation of the effects of PARP inhibition of SC10914 by the peripheral blood mononuclear cells（PBMC） 8 weeks Evaluation of the antitumor effects of SC10914 as measured by overall response rate (ORR) 8 weeks Evaluation of the antitumor effects of SC10914 as measured by progression free survival (PFS) 8 weeks Evaluation of the antitumor effects of SC10914 as measured by duration of response (DOR) 8 weeks Evaluation of the antitumor effects of SC10914 as measured by time to progression (TTP) 8 weeks Evaluation of the antitumor effects of SC10914 as measured by overall survival (OS) Baseline until death Evaluation of the antitumor effects of SC10914 as measured by tumor markers CA-125 as assessed by Gynecologic Cancer Intergroup(GCIG) 8 weeks Evaluation of the antitumor effects of SC10914 as measured by tumor markers PSA as assessed by Prostate-Specific Antigen Working Group(PSAWG) 8 weeks
Trial Locations
- Locations (1)
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China