Clinical trial NCT04830501: Study of the of the Safety and Tolerability of TT-00434 in Patients With Advanced Solid Tumors
Official title: A Phase I Study of the Safety, Tolerability, Pharmacokinetics Profile, and Preliminary Efficacy of TT-00434 in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: TransThera Sciences (Nanjing), Inc.
Sponsor class: INDUSTRY
First posted: 2021-04-05
Enrollment: 11
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 20 years.
* Patients must have a histological or cytologically confirmed diagnosis of advanced or recurrent malignant solid tumors.
* Patients have received all currently available standard treatments (unless the therapy is contraindicated, intolerable or unavailable due to any reasons).
* Patients must have measurable or evaluable disease (according to RECIST 1.1)
* Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
* Must agree to take sufficient contraceptive methods to avoid pregnancy during the study and until at least 6 months after ceasing study treatment
* Patients must have fully understood and voluntarily signed informed consent form (ICF) for this study.

Exclusion Criteria:

* Patients who received other investigational products or devices in other clinical trials within 4 weeks before the first dose.
* 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.
* 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).
* Patients who have gastrointestinal disorders that will affect oral administration or the Investigator judges that the absorption of TT-00434 will be interfered.
* Patients underwent major surgery (except biopsy) within 4 weeks, or the surgical incision has not completely healed prior to the first dose.
* Patients who have active bacterial or fungal infections (CTCAE, Grade ≥ 2) that required systemic treatment within 2 weeks prior to the first dose.
* Patients who have active HBV infection (HBV DNA copies ≥ ULN) and/or HCV infection (HCV RNA copies ≥ ULN)
* Patients who test positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome.
* Has received a live-virus vaccination within 30 days of planned first dose NOTE: Seasonal flu vaccines are permitted.
* Known or suspected drug hypersensitivity to any ingredients of TT-00434 tablets.
* Female patients in pregnancy or lactation. Male patients or female patients at reproductive ages who are unwilling to receive effective contraceptive measures.
* Patients who are judged by the Investigator to be unsuitable for this study.

Primary outcomes:
measure: Dose Limiting Toxicity (DLT)
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Incidence of AEs
timeFrame: up to 30 days from study discontinuation
Secondary outcomes:
measure: Peak Plasma Concentration (Cmax)
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Time of first Occurance of Cmax（tmax)
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Serum phosphate levels
timeFrame: up to 30 days from study discontinuation
measure: Objective response rate (ORR)
timeFrame: through study completion, an average of 1 year
measure: Disease control rate (DCR)
timeFrame: through study completion, an average of 1 year
measure: Progression Free Survival (PFS)
timeFrame: through study completion, an average of 1 year
measure: Overall Survival (OS)
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: Taipei Medical University Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
Study officials:
affiliation: Taipei Medical University Hospital
name: Huey En Tzeng
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cheng-Kung University Hospital
name: Chia Jui Yen
role: PRINCIPAL_INVESTIGATOR
affiliation: Tri-Service General Hospital
name: Ching Liang Ho
role: PRINCIPAL_INVESTIGATOR
affiliation: Taipei Medical University Hospital
name: Ming Che Liu
role: PRINCIPAL_INVESTIGATOR
References: