Ningetinib (CT053PTSA) Plus Gefitinib in Stage IIIB or IV NSCLC Patients With EGFR Mutation and T790M Negative

NCT03758287 | Unknown Phase 1

• 1 other identifier: PCD-DCT053-16-001
• Study Type: interventional
• Target: 158
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase Ib, multi-center, open label study evaluating the safety and efficacy of CT053PTSA in combination with gefitinib in patients with EGFR mutation, T790M negative NSCLC who have progressed after EGFR TKI treatment.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Part 1（dose-escalation part）: Maximum Tolerated Dose (MTD)

  The maximum tolerated dose (MTD) of the CT053PTSA and gefitinib combination will be determined according to incidence of dose-limiting toxicity (DLT) assessed by NCI CTCAE v4.03

  Cycle 1 Day 1 to Cycle 1 Day 28

• Part 2（expansion part）: Overall Response Rate

  Overall response rate (ORR), defined as a partial response (PR) or complete response (CR) occurring at any point post-treatment according to Response Evaluation Criteria in Solid Tumors as assessed by RECIST v1.1

  up to approximately 36 months

Secondary Outcomes (8)

• Number of patients with adverse events (AEs) as a measure of safety and tolerability

  up to approximately 36 months

• Disease Control Rate (DCR)

  up to approximately 36 months

• Progression-free Survival (PFS)

  up to approximately 36 months

• Duration of Response (DOR)

  up to approximately 36 months

• Overall Survival (OS)

  up to approximately 60 months

Study Arms (1)

CT053PTSA +Gefitinib

EXPERIMENTAL

Patients will receive CT053PTSA and gefitinib over a 28-day cycle until progressive disease, intolerable toxicity or subject's withdrawal from treatment. CT053PTSA will be administered daily, at a dose of 30 mg/40mg/60mg orally . Gefitinib will be administered daily, at a dose of 250 mg orally .

Drug: CT053PTSA; Drug: Gefitinib

Interventions

CT053PTSA DRUG

Also known as: Ningetinib

CT053PTSA +Gefitinib

Gefitinib DRUG

Also known as: Iressa

CT053PTSA +Gefitinib

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed Stage IIIB or IV NSCLC
• Resistance to EGFR TKI (1st, 2nd or 3rd generation)
• Histological or cytological evidence of EGFR mutation and T790M negative after progression on last EGFR TKI therapy
• c-Met GCN ≥ 6 or cluster amplification is required if participant is resistant to1st or 2nd generation EGFR-TKI ;c-MET GCN statue is not required, If participant is resistant to3rd generation EGFR-TKI （osimertinib）；
• Measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
• Toxicity recovered to NCI CTCAE v.4.03 Grade ≤1 from previous treatments (except alopecia)
• ECOG performance status (PS) 0 or 1
• Life expectancy of ≥ 12 weeks
• Adequate organ function

You may not qualify if:

• Prior treatments
• Chemotherapy, targeted therapy (except EGFR TKI), immunotherapy, radiotherapy, or major surgery within 4 weeks prior to study treatment
• Nitrosourea and mitomycin chemotherapy within 6 weeks prior to study treatment
• EGFR TKI treatment within 2 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 Axl inhibitor (eg, crizotinib, cabozantinib, volitinib, INC280)
• 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)
• Interstitial pneumonia or radiation pneumonitis
• Uncontrolled hypertension that require more than two anti-hypertensive agents to control, or systolic blood pressure (BP) \>140mmHg or diastolic BP \>90 mmHg before the first administration (BP is the mean blood pressure of two measures that 1 hours interval or above)
• Doppler ultrasound evaluation：Left ventricular ejection fraction \< 50%
• Grade ≥ 2 of arrhythmia (assessed by NCI CTCAE 4.03), 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 and gefitinib (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

Sponsors & Collaborators

• Sunshine Lake Pharma Co., Ltd.: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Gefitinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

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: November 27, 2018
• First Posted: November 29, 2018
• Study Start: November 1, 2016
• Primary Completion: July 17, 2023
• Study Completion: July 17, 2023
• Last Updated: June 22, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)