Study of the of the Safety and Tolerability of TT-00434 in Patients With Advanced Solid Tumors
Study Details
Study Description
Brief Summary
This is a phase I study of the safety, tolerability, pharmacokinetics profile, and preliminary efficacy of TT-00434 in patients with advanced solid tumors.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
This is a phase I, First-in-Human (FIH), open-label, dose escalation clinical study in patients who have a histological or cytologically confirmed diagnosis of advanced or recurrent tumors that all standard treatments have been used or are not feasible. It aims to determine the maximum tolerated dose (MTD) and/or the recommended phase 2 dose (RP2D) for study, evaluate the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) characteristics and the preliminary anti-tumor activity of TT-00434, and explore the relationship between the anti-tumor activity of TT-00434 and the tumor FGFR alterations.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dose Escalation This study adopts an accelerated titration design (ATD) and utilizes an accelerated dose escalation phase in order to minimize suboptimal drug exposures, followed by a conventional 3+3 dose escalation phase to achieve MTD. |
Drug: TT-00434
Once daily [QD], 28 days/cycle.
|
Outcome Measures
Primary Outcome Measures
- Dose Limiting Toxicity (DLT) [At the end of Cycle 1 (each cycle is 28 days)]
Safety and tolerability
- Incidence of AEs [up to 30 days from study discontinuation]
Safety and tolerability
Secondary Outcome Measures
- Peak Plasma Concentration (Cmax) [At the end of Cycle 1 (each cycle is 28 days)]
PK evaluation
- Area under the plasma concentration versus time curve (AUC) [At the end of Cycle 1 (each cycle is 28 days)]
PK evaluation
- Time of first Occurance of Cmax（tmax) [At the end of Cycle 1 (each cycle is 28 days)]
PK evaluation
- Serum phosphate levels [up to 30 days from study discontinuation]
PD biomarker
- Objective response rate (ORR) [through study completion, an average of 1 year]
Assess anti-tumor activity
- Disease control rate (DCR) [through study completion, an average of 1 year]
Assess anti-tumor activity
- Progression Free Survival (PFS) [through study completion, an average of 1 year]
Assess anti-tumor activity
- Overall Survival (OS) [through study completion, an average of 1 year]
Assess anti-tumor activity
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age ≥ 20 years.
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Patients must have a histological or cytologically confirmed diagnosis of advanced or recurrent malignant solid tumors.
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Patients have received all currently available standard treatments (unless the therapy is contraindicated, intolerable or unavailable due to any reasons).
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Patients must have measurable or evaluable disease (according to RECIST 1.1)
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Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
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Must agree to take sufficient contraceptive methods to avoid pregnancy during the study and until at least 6 months after ceasing study treatment
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Patients must have fully understood and voluntarily signed informed consent form (ICF) for this study.
Exclusion Criteria:
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Patients who received other investigational products or devices in other clinical trials within 4 weeks before the first dose.
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Patients who received anti-tumor therapy within 4 weeks, or within 5-half-lives (which is longer) before the first dose, including but not limited to chemotherapy, radiotherapy (palliative radiotherapy is completed at least 2 weeks before the first dose can enrol), targeted therapy or immunotherapy.
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Patients who have previous toxicity of anti-tumor therapy that has not recovered to Grade 1. (except for ≤ Grade 2 alopecia, chemotherapy-induced peripheral neurotoxicity, and ototoxicity).
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Patients who have gastrointestinal disorders that will affect oral administration or the Investigator judges that the absorption of TT-00434 will be interfered.
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Patients underwent major surgery (except biopsy) within 4 weeks, or the surgical incision has not completely healed prior to the first dose.
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Patients who have active bacterial or fungal infections (CTCAE, Grade ≥ 2) that required systemic treatment within 2 weeks prior to the first dose.
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Patients who have active HBV infection (HBV DNA copies ≥ ULN) and/or HCV infection (HCV RNA copies ≥ ULN)
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Patients who test positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome.
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Has received a live-virus vaccination within 30 days of planned first dose NOTE: Seasonal flu vaccines are permitted.
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Known or suspected drug hypersensitivity to any ingredients of TT-00434 tablets.
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Female patients in pregnancy or lactation. Male patients or female patients at reproductive ages who are unwilling to receive effective contraceptive measures.
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Patients who are judged by the Investigator to be unsuitable for this study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | National Cheng Kung University Hospital | Tainan | Taiwan | ||
| 2 | Taipei Medical University Hospital | Taipei | Taiwan | ||
| 3 | Tri-Service General Hospital | Taipei | Taiwan |
Sponsors and Collaborators
- TransThera Sciences (Nanjing), Inc.
Investigators
- Principal Investigator: Huey En Tzeng, Taipei Medical University Hospital
- Principal Investigator: Chia Jui Yen, National Cheng-Kung University Hospital
- Principal Investigator: Ching Liang Ho, Tri-Service General Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TT00434CN01