Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of Ningetinib (CT053PTSA) in Patients With Advanced Solid Tumors: A Phase I, Single-arm, Single-center, Open-label, Dose-escalation Study
Overview
- Phase
- Phase 1
- Intervention
- CT053PTSA
- Conditions
- Advanced Solid Tumors
- Sponsor
- Sunshine Lake Pharma Co., Ltd.
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Maximum Tolerated Dose (MTD)
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
This is a phase I, single-arm, single-center, open-label, dose-escalation Study evaluating the safety and efficacy of CT053PTSA in patients with Advanced Solid Tumors
Detailed Description
This is a dose-escalation study. The primary purpose is to determine the dose limiting toxicity (DLT), maximum tolerated dose (MTD) and recommend doses and regimen of CT053PTSA for further studies.
Investigators
Eligibility Criteria
Inclusion Criteria
- •A. Subjects with advanced solid tumors confirmed by histologically or cytologically that are refractory to current treatment or for which there is not a current standard of care B. Toxicity recovered to NCI CTCAE v.4.0 Grade ≤1 from previous treatments (chemotherapy, radiotherapy or surgery) C. ECOG performance status (PS) 0 or 1 D. Life expectancy of ≥ 12 weeks E. Adequate organ function
- •Hemoglobin \> 9 g/dL (SI Units: 90 g/L) without transfusion support or growth factors; Platelet count ≥ 100 × 10\^9/L; Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L without growth factor support.
- •AST/SGOT and/or ALT/SGPT≤ 2.5 × upper limit of normal (ULN) or ≤ 5.0× ULN if liver metastases are present; serum bilirubin ≤ 1.5×ULN
- •Serum creatinine ≤ 1.5×ULN
- •Blood potassium≥ 3.0 mmol/L; serum calcium≥2.0 mmol/L
- •Fasting serum triglyceride level≤5.7 mmol/L
- •Asymptomatic abnormal serum amylase≤1.5×ULN
- •Serum lipase≤ ULN
- •INR≤ 1.5×ULN；APTT≤ 1.5×ULN； PT ≤ 1.5×ULN
Exclusion Criteria
- •Chemotherapy, immunotherapy, radiotherapy, or major surgery within 4 weeks prior to study treatment
- •Nitrosourea, anthracyclinea and mitomycin chemotherapy within 6 weeks prior to study treatment
- •Had received live vaccine within 4 weeks prior to study treatment
- •Had received any investigational agent from other clinical study within 4 weeks prior to study treatment or are currently participating in other clinical trials
- •Previous treatment with any other c-MET inhibitor or HGF inhibitor
- •Symptomatic, untreated or unstable central nervous system metastases
- •Spinal cord compression, carcinomatous meningitis or leptomeningeal diseaseonly (patient are only permitted if treated, asymptomatic and stable for at least 4 weeks prior to start of study treatment)
- •Patients with hypertension that can't be well controlled by drugs (systolic blood pressure\> 140 mmHg or diastolic blood pressure\> 90 mmHg)
- •Doppler ultrasound evaluation：Left ventricular ejection fraction \< 50%
- •Grade ≥ 2 of arrhythmia (assessed by NCI CTCAE 4.0), or symptomatic bradycardia, or male with QTCF \> 450 ms or female with QTCF \> 470 ms, or patients with a history of torsion or congenital QT prolonged syndrome long QT syndrome
Arms & Interventions
CT053PTSA (dose escalation)
Patients were treated in 5 dose cohorts of 15 mg, 30 mg, 60 mg, 100 mg, and 150 mg QD capsules. Patients receive treatment with CT053PTSA once on Cycle 0 Day 1 following a 7-day treatment-free withdrawal period to observe the safety and pharmacokinetic of CT053PTSA. After that, Patients receive treatment with CT053PTSA per orally, beginning on Cycle 1 Day 1 for 28 day following a 7-day treatment-free withdrawal period to observe efficacy of CT053PTSA and determine to continue taking medicine or not. Each cycle had 28 days.
Intervention: CT053PTSA
Outcomes
Primary Outcomes
Maximum Tolerated Dose (MTD)
Time Frame: Cycle 0 Day 1 to Cycle 1 Day 28
The maximum tolerated dose (MTD) of the CT053PTSA will be determined according to incidence of dose-limiting toxicity (DLT) assessed by NCI CTCAE v4.0
Secondary Outcomes
- Pharmacokinetics (PK) of CT053PTSA_Tmax(Cycle 0 Day 1 to Cycle 1 Day 28)
- Efficacy of CT053PTSA_ORR(up to approximately 36 months)
- Pharmacokinetics (PK) of CT053PTSA_AUC(Cycle 0 Day 1 to Cycle 1 Day 28)
- Efficacy of CT053PTSA_DCR(up to approximately 36 months)
- Pharmacokinetics (PK) of CT053PTSA_Cmax(Cycle 0 Day 1 to Cycle 1 Day 28)