First-In-Human Phase I Trial of Ningetinib ( CT053PTSA ) in the Patients With Advanced Solid Tumors

Advanced Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04577703
• Other study ID #: PCD-DCT053-12-003
• Status: Completed
• Phase: Phase 1
• Start date: February 8, 2014
• Est. completion date: December 10, 2015

Study information

• Verified date: September 2020
• Source: Sunshine Lake Pharma Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: December 10, 2015
• Est. primary completion date: December 10, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Drug:
• CT053PTSA
CT053PTSA will be administered daily in fasting state

Locations

Country	Name	City	State
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sunshine Lake Pharma Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD)	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	Cycle 0 Day 1 to Cycle 1 Day 28
Secondary	Pharmacokinetics (PK) of CT053PTSA_Cmax	To evaluate the Pharmacokinetics (PK) of CT053PTSA with Maximum observed plasma concentration (Cmax)	Cycle 0 Day 1 to Cycle 1 Day 28
Secondary	Pharmacokinetics (PK) of CT053PTSA_Tmax	To evaluate the Pharmacokinetics (PK) of CT053PTSA with Time of maximum observed plasma concentration (Tmax).	Cycle 0 Day 1 to Cycle 1 Day 28
Secondary	Pharmacokinetics (PK) of CT053PTSA_AUC	To evaluate the Pharmacokinetics (PK) of CT053PTSA with Area under the plasma concentration time curve (AUC).	Cycle 0 Day 1 to Cycle 1 Day 28
Secondary	Efficacy of CT053PTSA_ORR	To assess overall response rate (ORR) for patients treated CT053PTSA.	up to approximately 36 months
Secondary	Efficacy of CT053PTSA_DCR	To assess disease control rate (DCR) for patients treated CT053PTSA.	up to approximately 36 months