Advanced Solid Tumors
Conditions
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.
Interventions
DRUGCT053PTSA
CT053PTSA will be administered daily in fasting state
Sponsors
Sunshine Lake Pharma Co., Ltd.
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
\- 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 1. 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. 2. 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 3. Serum creatinine ≤ 1.5×ULN 4. Blood potassium≥ 3.0 mmol/L; serum calcium≥2.0 mmol/L 5. Fasting serum triglyceride level≤5.7 mmol/L 6. Asymptomatic abnormal serum amylase≤1.5×ULN 7. Serum lipase≤ ULN 8. INR≤ 1.5×ULN；APTT≤ 1.5×ULN； PT ≤ 1.5×ULN
Exclusion criteria
1. Chemotherapy, immunotherapy, radiotherapy, or major surgery within 4 weeks prior to study treatment 2. Nitrosourea, anthracyclinea and mitomycin chemotherapy within 6 weeks prior to study treatment 3. Had received live vaccine within 4 weeks prior to study treatment 4. Had received any investigational agent from other clinical study within 4 weeks prior to study treatment or are currently participating in other clinical trials 5. Previous treatment with any other c-MET inhibitor or HGF inhibitor 6. Symptomatic, untreated or unstable central nervous system metastases 7. 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) 8. Patients with hypertension that can't be well controlled by drugs (systolic blood pressure\> 140 mmHg or diastolic blood pressure\> 90 mmHg) 9. Doppler ultrasound evaluation：Left ventricular ejection fraction \< 50% 10. 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 11. Certain factors that would preclude adequate absorption of CT053PTSA (eg. unable to swallow, chronic diarrhea, intestinal obstruction) 12. Significant hemoptysis within 2 months prior to enrollment, or a daily hemoptysis volume is 2.5 ml or above 13. Patients with evidence of bleeding tendency, including the following cases: gastrointestinal bleeding, hemorrhagic gastric ulcer, fecal occult blood ++ and above; or melena or hematemesis within 2 months; or visceral bleeding that may occur considered by investigator 14. History of immunodeficiency, or other acquired or congenital immunodeficiency, or history of organ transplantation 15. Any disease of the following bellowed within 12 months prior to administration: Myocardial infarction, severe angina, or unstable angina, coronary or peripheral artery bypass graft, congestive heart failure, or cerebrovascular events (including transient ischemic attack) 16. Pulmonary embolism within 6 months prior to administration 17. Active infection of hepatitis B, hepatitis C, or infection of HIV 18. Undergone a bone marrow or solid organ transplant. 19. Patients with severe retinopathy or exfoliation in the investigator's judgment 20. Patients need to be supplemented with stem cells before receiving large dose chemotherapy (except for myeloma or lymphoma) 21. History of thyroid dysfunction, and the thyroid function cannot be maintained at the normal range with drugs. 22. Anticoagulants, vitamin K antagonists, other anti-tumor drugs and drugs that prolong the QT interval are not allowed. 23. Serious electrolyte imbalance in the investigator's judgment 24. Pregnant or lactating woman 25. Any other reason the investigator considers the patient is not suitable to participate in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) | 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
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK) of CT053PTSA_Cmax | Cycle 0 Day 1 to Cycle 1 Day 28 | To evaluate the Pharmacokinetics (PK) of CT053PTSA with Maximum observed plasma concentration (Cmax) |
| Pharmacokinetics (PK) of CT053PTSA_Tmax | Cycle 0 Day 1 to Cycle 1 Day 28 | To evaluate the Pharmacokinetics (PK) of CT053PTSA with Time of maximum observed plasma concentration (Tmax). |
| Pharmacokinetics (PK) of CT053PTSA_AUC | Cycle 0 Day 1 to Cycle 1 Day 28 | To evaluate the Pharmacokinetics (PK) of CT053PTSA with Area under the plasma concentration time curve (AUC). |
| Efficacy of CT053PTSA_ORR | up to approximately 36 months | To assess overall response rate (ORR) for patients treated CT053PTSA. |
| Efficacy of CT053PTSA_DCR | up to approximately 36 months | To assess disease control rate (DCR) for patients treated CT053PTSA. |
Countries
China
Outcome results
None listed