TR128 in Patients With Advanced Solid Tumors
Study Details
Study Description
Brief Summary
This is a open-label, 3+3 design, dose escalation and expansion, phase I study, to evaluate the safety and tolerability, and to determine the RP2D of TR128 when administered qd in patients with advanced solid tumors. Up to 5 cohorts of 3-6 patients each will be treated in dose escalation phase of the study. One cycle is 28 days. Dose expansion phase to further evaluate the safety, tolerability and preliminary anti-tumor activity of TR128 at the RP2D.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
This phase I study of TR128 will investigate the tolerability, safety, pharmacokinetics (PK) and preliminary efficacy of TR128, and will define the maximum tolerated dose (MTD) of TR128 using 3+3 design. A dose expansion phase will identify the recommended phase 2 dose. In this clinical study, TR128 is given orally daily. A treatment cycle is defined as 28 days. Patients will receive study treatment until criteria for study termination are met. A safety follow-up visit will be conducted 28 days after the last dose of study treatment. Patients who discontinue study treatment for reasons other disease progression will have post-treatment follow-up for disease assessment until start of new anticancer treatment, patient withdraws consent, is lost to follow-up, death, or until the sponsor stops the study, whichever comes first.
Adverse events (AEs) will be assessed using the NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0.
Tumor response will be assessed by computed tomography (CT) and /or magnetic resonance imaging (MRI) scan using RECIST1.1 criteria, assessed by the investigator.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: TR128
|
Drug: TR128
TR128 will be given daily for 28 days in 28-day cycles until there appears evidence of progressive disease, intolerable toxicity, or the subject discontinues from the study treatment for other reasons. Starting dose is 100mg, with escalation to 500mg.
|
Outcome Measures
Primary Outcome Measures
- Adverse Events and Serious Adverse Events [from the first dose to within 30 days after the last dose]
Frequency, duration, and severity of Adverse Events and Serious Adverse Events evaluated by NCI CTCAE v5.0
- Dose limited toxicities [within 28 days after the first dose]
Incidence of dose limited toxicities
- Maximum tolerated dose [Throughout the study for approximately 2 years]
Evaluated by safety review committee
- Recommended phase II dose [Throughout the study for approximately 2 years]
Evaluated by safety review committee
Secondary Outcome Measures
- AUClast [within 31 days after the first dose]
Characterize the pharmacokinetic profile of TR128
- AUCinf [whithin 31 days after the first dose]
Characterize the pharmacokinetic profile of TR128
- Cmax [whithin 31 days after the first dose]
Characterize the pharmacokinetic profile of TR128
- Tmax [within 31 days after the first dose]
Characterize the pharmacokinetic profile of TR128
- CL/F [whithin 31 days after the first dose]
Characterize the pharmacokinetic profile of TR128
- Vz/F [within 31 days after the first dose]
characterize the pharmacokinetic profile of TR128
- Terminal half-life (T1/2) [whithin 31 days after the first dose]
Characterize the pharmacokinetic profile of TR128
- ORR [throughout the study for approximately 2 years]
Efficacy-overall response rate
- PFS [throughout the study for approximately 2 years]
Efficacy-progression free survival
- DOR [throughout the study for approximately 2 years]
Efficacy-duration of response
- DCR [throughtout the study for approximately 2 years]
Efficacy-disease control rate
Eligibility Criteria
Criteria
Inclusion Criteria:
-
fully understand the procedures of the clinical study and participate voluntarily with signed and dated written informed consent form, comply with the requirements of the study protocol.
-
males and/or females at least 18 years old when signing the informed consent form.
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histologically or cytologically confirmed patients with advanced malignant solid tumors, eligible patients must have failed standard treatment, no standard treatment, or not suitable for standard treatment at this stage as determined by the investigator.
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measurable disease with at least one leasion amenable to response assessment per RECIST 1.1.
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eastern cooperative oncology group performance status (ECOG) ≤1 at screening.
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life expectancy of at least 3 months.
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acceptable organ function: Absolute neutrophil count(ANC)≥1.5×109/L; Platelet count(PLT)≥90×109/L; Hemoglobin(Hb)≥90 g/L; INR or PT≤1.5×Upper limit of normal value (ULN), APTT≤1.5×ULN ; Total bilirubin(TBIL)≤1.5×Upper limit of normal value(ULN) (≤3× ULN if there is liver involvement); Alanine aminotransferase(ALT)≤2.5×ULN and aspartate aminotransferase(AST)≤2.5×ULN (≤ 5 × ULN if there is liver involvement); Cr ≤1.5×ULN or CCr ≥50 ml/min (calculated by Cockcroft-Gault formula).
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fertile male and female must agree to use medically approved contraceptives during the study and within 6 months after the last dose of the study.
Exclusion Criteria:
-
medical history and surgical history excluded according to the protocol.
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any previous medical treatment history exclude from the protocol.
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abnormal laboratory results exclude from the protocol.
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pregnant and lactating women (currently breast-feeding or less than six months after delivery although not breast-feeding).
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unsuitable for the study by the investigator's judgment.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Tarapeutics Science Inc.
Investigators
- Principal Investigator: Lin Shen, MD, PhD, Peking University Cancer Hospital & Institute
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TR128-CN-PI-01