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Evaluate Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of AZD3759

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ClinicalTrials.gov Identifier: NCT03360929
Recruitment Status : Recruiting
First Posted : December 4, 2017
Last Update Posted : May 29, 2019
Sponsor:
Collaborator:
Tigermed Consulting Co., Ltd
Information provided by (Responsible Party):
LYZZ Alpha Holding Ltd

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
Non Small Cell Lung Cancer Drug: AZD3759 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. Three dose cohorts include: 150, 250 and 300 mg 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 21 participants
Intervention Model: Single Group Assignment
Intervention Model Description: This is a multi-center, open-label, dose escalation and phase II study, consisting of dose escalation study in Part A and phase II study in Part B.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II, Open-label, Multi-center Study to Evaluate Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of AZD3759 in Chinese Patients With EGFRm+ NSCLC With Central Nervous System (CNS) Metastases
Actual Study Start Date : October 30, 2017
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : June 30, 2020

Resource links provided by the National Library of Medicine


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. Three dose cohorts are planned for dose escalation, including: 150, 250 and 300 mg twice daily.

RP2D in dose expansion.

Drug: AZD3759
Strength: 50mg/tablet, 100mg/tablet Dosage and administration: Twice daily administration under fasting state.




Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 21 days after the first dose ]
    AE.SAE,vital signs, physical examination,laboratory examinations etc.

  2. anti-tumor activity [ Time Frame: every 6 weeks ]
    ORR, DCR, DOR, PFS and tumor size changing compared with baseline according to RECIST 1.1


Secondary Outcome Measures :
  1. Peak Plasma Concentration (Cmax) [ Time Frame: 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)

  2. Area under the plasma concentration versus time curve (AUC) [ Time Frame: 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)



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Subjects must provide written informed consent before any study related procedure.
  2. Male or female Chinese patients ≥18 years old.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. LM patients must have at least one leptomeningeal lesion which shows visible abnormality by MRI. Measurable extracranial disease is not required.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03360929


Contacts
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Contact: John Ge, M.D. 021 63862197 john.ge@alphabiopharma.com.cn
Contact: Yang Lu, M.D. 021 63862181 yang.lu@alphabiopharma.com.cn

Locations
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China, Guangdong
Guangdong General Hospital Recruiting
Guangzhou, Guangdong, China, 510080
Contact: Qing Q Zhou    8620-83827812      
China, Hubei
0004 Recruiting
Wuhan, Hubei, China
China, Hunan
0002 Recruiting
Changsha, Hunan, China
China, Zhejiang
0003 Recruiting
Hangzhou, Zhejiang, China
Sponsors and Collaborators
LYZZ Alpha Holding Ltd
Tigermed Consulting Co., Ltd
Investigators
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Principal Investigator: Yilong Wu, Professor Guangdong General Hospital
  Study Documents (Full-Text)

Documents provided by LYZZ Alpha Holding Ltd:

Publications:
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Responsible Party: LYZZ Alpha Holding Ltd
ClinicalTrials.gov Identifier: NCT03360929     History of Changes
Other Study ID Numbers: AZD3759-001
First Posted: December 4, 2017    Key Record Dates
Last Update Posted: May 29, 2019
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is not a plan to make IPD available.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by LYZZ Alpha Holding Ltd:
Lung Cancer

Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms