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

NCT04577703 | Completed Phase 1

• 1 other identifier: PCD-DCT053-12-003
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Pharmacokinetics (PK) of CT053PTSA_Cmax

  Cycle 0 Day 1 to Cycle 1 Day 28

• Pharmacokinetics (PK) of CT053PTSA_Tmax

  Cycle 0 Day 1 to Cycle 1 Day 28

• Pharmacokinetics (PK) of CT053PTSA_AUC

  Cycle 0 Day 1 to Cycle 1 Day 28

• Efficacy of CT053PTSA_ORR

  up to approximately 36 months

• Efficacy of CT053PTSA_DCR

  up to approximately 36 months

Study Arms (1)

CT053PTSA (dose escalation)

EXPERIMENTAL

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.

Drug: CT053PTSA

Interventions

CT053PTSA DRUG

CT053PTSA will be administered daily in fasting state

Also known as: Ningetinib

CT053PTSA (dose escalation)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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

You may not qualify if:

• 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
• Certain factors that would preclude adequate absorption of CT053PTSA (eg. unable to swallow, chronic diarrhea, intestinal obstruction)
• Significant hemoptysis within 2 months prior to enrollment, or a daily hemoptysis volume is 2.5 ml or above
• 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
• History of immunodeficiency, or other acquired or congenital immunodeficiency, or history of organ transplantation
• 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)

Sponsors & Collaborators

• Sunshine Lake Pharma Co., Ltd.: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Study Officials

• Li Zhang, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2020
• First Posted: October 8, 2020
• Study Start: February 8, 2014
• Primary Completion: December 10, 2015
• Study Completion: December 10, 2015
• Last Updated: October 8, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)