Clinical trial NCT02940132: A Study of SC10914 in Patients With Advanced Solid Tumors
Official title: Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics/ Pharmacodynamics and Preliminary Efficacy of SC10914 in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: Jiangxi Qingfeng Pharmaceutical Co. Ltd.
Sponsor class: INDUSTRY
First posted: 2016-10-20
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Dose Escalation Study: Maximum-tolerated Dose (MTD) of SC10914
timeFrame: 30 days
measure: Dose Expansion Study: Recommended Phase II Dose(RP2D) of SC10914
timeFrame: 8 weeks
Secondary outcomes:
measure: Number of participants with treatment-related adverse events (AEs) as assessed by NCI-CTCAE v4.03
timeFrame: 8 weeks
measure: Area under the concentration-time curve (AUC)
timeFrame: 4 weeks
measure: Time to reach maximum concentration (Tmax)
timeFrame: 4 weeks
measure: Maximum Concentration (Cmax)
timeFrame: 4 weeks
measure: Trough Concentration (Ctrough)
timeFrame: 4 weeks
measure: Elimination Half-Life (T½)
timeFrame: 4 weeks
measure: Clearance (CL)
timeFrame: 4 weeks
measure: Volume of Distribution (Vd)
timeFrame: 4 weeks
measure: Evaluation of the effects of PARP inhibition of SC10914 by the peripheral blood mononuclear cells（PBMC）
timeFrame: 8 weeks
measure: Evaluation of the antitumor effects of SC10914 as measured by overall response rate (ORR)
timeFrame: 8 weeks
measure: Evaluation of the antitumor effects of SC10914 as measured by disease control rate (DCR)
timeFrame: 8 weeks
measure: Evaluation of the antitumor effects of SC10914 as measured by progression free survival (PFS)
timeFrame: 8 weeks
measure: Evaluation of the antitumor effects of SC10914 as measured by duration of response (DOR)
timeFrame: 8 weeks
measure: Evaluation of the antitumor effects of SC10914 as measured by time to progression (TTP)
timeFrame: 8 weeks
measure: Evaluation of the antitumor effects of SC10914 as measured by overall survival (OS)
timeFrame: Baseline until death
measure: Evaluation of the antitumor effects of SC10914 as measured by tumor markers CA-125 as assessed by Gynecologic Cancer Intergroup(GCIG)
timeFrame: 8 weeks
measure: Evaluation of the antitumor effects of SC10914 as measured by tumor markers PSA as assessed by Prostate-Specific Antigen Working Group(PSAWG)
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Lin Shen
role: PRINCIPAL_INVESTIGATOR
References: