Advanced Solid Tumor
Conditions
Brief summary
This is a open-label, dose escalation, accelerated titration combined 3+3 design, phase I study, to evaluate the safety and tolerability, and to determine the RP2D of TR64 when administered qd in patients with advanced solid tumors. Up to 6 cohorts of 1-6 or 3-6 patients each will be treated in the study.
Detailed description
Patients will receive study treatment until criteria for study termination are met. A Safety Follow-up Visit will be conducted 28 days (±7 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 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 RECIST 1.1 criteria, assessed by the investigator.
Interventions
DRUGTR64
TR64 tablets 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.
Sponsors
Tarapeutics Science Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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. * 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. * Measurable disease with at least one lesion amenable to response assessment per RECIST 1.1. * Eastern cooperative oncology group performance status (ECOG) ≤2 at screening. * Life expectancy of at least 3 months. * Acceptable organ function: Absolute neutrophil count(ANC)≥1.5×109/L; Platelet count(PLT)≥90×109/L; Hemoglobin(Hb)≥90 g/L; Total bilirubin(TBIL)≤1.5×Upper limit of normal value(ULN); Alanine aminotransferase(ALT)≤2.5×ULN; Aspartate aminotransferase(AST)≤2.5×ULN; Creatinine clearance ≥50ml/min. * Fertile male and female must agree to use medically approved contraceptives during the study and within 90 days after the last dose of the study.
Exclusion criteria
* Known or suspected allergies to any of the investigational drug composition. * Medical history and surgical history excluded according to the protocol. * Any previous medical treatment history exclude from the protocol. * Abnormal laboratory results exclude from the protocol. * pregnant and lactating women (currently breast-feeding or less than six months after delivery although not breast-feeding). * Subjects may not be able to complete the study duo to poor compliance or other reasons, or unsuitable for the study by the investigator's judgment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose limited toxicities | within 28 days after the first dose | Incidence of dose limited toxicities |
| Adverse Events and Serious Adverse Events | From the first dose to within 28 days after the last dose | Frequency, duration and severity of Adverse Events and Serious Adverse Events evaluated by NCI CTCAE v5.0 |
| Recommended phaseII dose | Throughout the study for approximately 2 years | Evaluated by safety review committee |
| Maximum tolerated dose | Throughout the study for approximately 2 years | Evaluated by safety review committee |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CL/F | within 35 days after the first dose | Characterize the pharmacokinetic profile of TR64 |
| Vz/F | within 35 days after the first dose | Characterize the pharmacokinetic profile of TR64 |
| Terminal half-life (T1/2) | within 35 days after the first dose | Characterize the pharmacokinetic profile of TR64 |
| Tmax | within 35 days after the first dose | Characterize the pharmacokinetic profile of TR64 |
| AUClast | within 35 days after the first dose | Characterize the pharmacokinetic profile of TR64 |
| AUCinf | within 35 days after the first dose | Characterize the pharmacokinetic profile of TR64 |
| Cmax | within 35 days after the first dose | Characterize the pharmacokinetic profile of TR64 |
Other
| Measure | Time frame | Description |
|---|---|---|
| ORR | Throughout the study for approximately 2 years | Efficacy-Overall Response Rate |
| CBR | Throughout the study for approximately 2 years | Efficacy-Clinical Benefit Rate |
| DOR | Throughout the study for approximately 2 years | Efficacy-Duration of Response |
| PFS | Throughout the study for approximately 2 years | Efficacy-Progression Free Survival |
Countries
China
Contacts
Primary ContactYang Shu, MD. BS.
Outcome results
None listed