Clinical trial NCT04577703: First-In-Human Phase I Trial of Ningetinib ( CT053PTSA ) in the Patients With Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: Sunshine Lake Pharma Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-10-08
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
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, 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.

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

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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: Cycle 0 Day 1 to Cycle 1 Day 28
Secondary outcomes:
measure: Pharmacokinetics (PK) of CT053PTSA_Cmax
timeFrame: Cycle 0 Day 1 to Cycle 1 Day 28
measure: Pharmacokinetics (PK) of CT053PTSA_Tmax
timeFrame: Cycle 0 Day 1 to Cycle 1 Day 28
measure: Pharmacokinetics (PK) of CT053PTSA_AUC
timeFrame: Cycle 0 Day 1 to Cycle 1 Day 28
measure: Efficacy of CT053PTSA_ORR
timeFrame: up to approximately 36 months
measure: Efficacy of CT053PTSA_DCR
timeFrame: up to approximately 36 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Li Zhang, MD
role: PRINCIPAL_INVESTIGATOR
References: