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

NCT ID: NCT04577703

Last Updated: 2020-10-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-08
• Study Completion Date: 2015-12-10

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.

Conditions

Advanced Solid Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

CT053PTSA

Intervention Type: DRUG

CT053PTSA will be administered daily in fasting state

Interventions

CT053PTSA

CT053PTSA will be administered daily in fasting state

Intervention Type: DRUG

Other Intervention Names

Ningetinib

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sunshine Lake Pharma Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Li Zhang, MD

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Countries

China

Other Identifiers

PCD-DCT053-12-003

Identifier Type: -

Identifier Source: org_study_id