Evaluate Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of AZD3759
Study Details
Study Description
Brief Summary
This is a multi-center, open-label, dose escalation and phase I/II study, consisting of dose escalation in Part A and phase II study in Part B.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Detailed Description
Dose escalation and dose expansion to determine safety and tolerability of AZD3759, and explore RP2D in treatment of Chinese patients with EGFRm+ NSCLC with CNS metastasis. Two dose cohorts include: 150 and 250mg twice daily. Subjects will receive multiple doses of AZD3759 for consecutively 21 days each cycle. Dose escalation is planned to be performed in a single center, and dose expansion in multiple centers.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: experimental group Study drug: AZD3759 Strength: 50mg/tablet, 100mg/tablet Dose escalation:A treatment cycle consists of consecutive 21 days of dosing. two dose cohorts are planned for dose escalation, including: 150 and 250 mg twice daily. RP2D in dose expansion. |
Drug: AZD3759
Strength: 50mg/tablet, 100mg/tablet Dosage and administration: Twice daily administration under fasting state.
|
Outcome Measures
Primary Outcome Measures
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [21 days after the first dose]
AE.SAE,vital signs, physical examination,laboratory examinations etc.
- anti-tumor activity [every 6 weeks]
ORR, DCR, DOR, PFS and tumor size changing compared with baseline according to RECIST 1.1
Secondary Outcome Measures
- Peak Plasma Concentration (Cmax) [Pre-dose and 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h(C0D2) and 48h(C0D3) after the first single-dose(C0D1) ;Pre-dose of C1D1,C1D8, C1D15, C1D21 and C2D1 and 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h post dose on C1D21 during multiple dosing.]
Peak Plasma Concentration (Cmax)
- Area under the plasma concentration versus time curve (AUC) [Pre-dose and 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h(C0D2) and 48h(C0D3) after the first single-dose(C0D1) ;Pre-dose of C1D1,C1D8, C1D15, C1D21 and C2D1 and 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h post dose on C1D21 during multiple dosing.]
Area under the plasma concentration versus time curve (AUC)
Eligibility Criteria
Criteria
Inclusion criteria:
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Subjects must provide written informed consent before any study related procedure.
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Male or female Chinese patients ≥18 years old.
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Histologically or cytologically confirmed non-small cell lung cancer with activating mutation in EGFR gene (including Exon19Del and/or L858R). A validated and robust test method reviewed and approved by the regulatory authority should be used to determine EGFR mutation status in tissue or plasma locally.
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Patients with advanced non-small cell lung cancer (stage IV) with documented BM and/or LM. Part A dose escalation can include EGFR TKI-naïve NSCLC patients with measurable lung lesion and no BM. Patients with BM and/or LM in each dose group shall account for at least one-third.
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According to Eastern Cooperative Oncology Group (ECOG) Scale, performance status is grade 0 to 1, without worsening in the past 2 weeks, and life expectancy of at least 3 months. If ECOG performance status is grade 2 due to LM disease, the patient can also be enrolled.
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Non-surgical sterilized women of child-bearing potential and male subjects shall agree to take medically acceptable contraception measures during dosing of investigational drug and 3 months after completion of study treatment. Non-surgical sterilized women of child-bearing potential must have negative blood pregnancy test at screening.
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Asymptomatic BM patients who have not received prior treatment with any EGFR TKI or symptomatic BM patients who are not warranted temporally for definitive local treatment (surgery or radiotherapy). For patients with prior local treatment for BM lesion (surgery or radiotherapy), intracranial lesion progression is required.
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BM patients must have at least one measurable intracranial lesion; in case of prior radiotherapy for BM lesion, progression is required and must meet measurable lesion criteria again. Measurable extracranial disease is not required.
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LM patients must be confirmed by the presence of malignant cells by cerebrospinal fluid (CSF) cytology. Diagnosis of LM disease by MRI alone does not meet inclusion criteria. Patients with both BM and LM are considered as LM.
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LM patients must have at least one leptomeningeal lesion which shows visible abnormality by MRI. Measurable extracranial disease is not required.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Guangdong General Hospital | Guangzhou | Guangdong | China | 510080 |
| 2 | 0004 | Wuhan | Hubei | China | |
| 3 | 0002 | Changsha | Hunan | China | |
| 4 | 0003 | Hangzhou | Zhejiang | China |
Sponsors and Collaborators
- LYZZ Alpha Holding Ltd
- Tigermed Consulting Co., Ltd
Investigators
- Principal Investigator: Yilong Wu, Professor, Guangdong Provincial People's Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
- Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993 Mar 3;85(5):365-76.
- Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
- Taphoorn MJ, Claassens L, Aaronson NK, Coens C, Mauer M, Osoba D, Stupp R, Mirimanoff RO, van den Bent MJ, Bottomley A; EORTC Quality of Life Group, and Brain Cancer, NCIC and Radiotherapy Groups. An international validation study of the EORTC brain cancer module (EORTC QLQ-BN20) for assessing health-related quality of life and symptoms in brain cancer patients. Eur J Cancer. 2010 Apr;46(6):1033-40. doi: 10.1016/j.ejca.2010.01.012. Epub 2010 Feb 22.
- AZD3759-001