Brief Title
Study Comparing WX-0593 to Crizotinib in ALK Positive Non-Small Cell Lung Cancer (NSCLC) Patients
Official Title
An Open-label, Randomized, Multicenter Phase 3 Study Comparing WX-0593 to Crizotinib in Anaplastic Lymphoma Kinase (ALK) Positive Non-Small Cell Lung Cancer (NSCLC) Patients
Brief Summary
The primary purpose of this study is to evaluate the efficacy and safety of WX-0593 vs.
crizotinib in patients with ALK-positive non-small cell lung cancer who had not received
prior systemic therapy
Detailed Description
To evaluate the efficacy and safety of WX-0593 vs. crizotinib in patients with ALK-positive
NSCLC who had not received prior systemic therapy, to obtain additional pharmacokinetic (PK)
data from sparse PK sampling, to compare the quality of life (QoL) in patients receiving
WX-0593 vs. crizotinib, to evaluate the status of exploratory biomarkers and correlate with
clinical outcome, and to obtain germline DNA samples for possible pharmacogenetic analysis in
the event that outliers with respect to efficacy, tolerability/safety, or exposure are
identified.
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
Progression-free Survival (PFS)
Secondary Outcome
Progression-free survival (PFS)
Condition
Non-small Cell Lung Cancer
Intervention
WX-0593 Tablets
Study Arms / Comparison Groups
WX-0593 Tablets
Description: Eligible patients with ALK+ NSCLC will receive WX-0593 tablets without food until documented disease progression or unacceptable toxicity. 60 mg of WX-0593 tablets, once daily for 7 days, followed by 180 mg of WX-0593 tablets, once daily in a 28-days cycle.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
330
Start Date
June 1, 2019
Completion Date
December 1, 2021
Primary Completion Date
June 1, 2021
Eligibility Criteria
Inclusion Criteria:
1. ≥18 years
2. Female or male
3. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
4. Life expectancy of at least 12 weeks.
5. At least one measurable lesion (according to RECIST v1.1)
6. Histologically or cytologically confirmed diagnosis of advanced or recurrent or
metastatic NSCLC that is ALK-positive by an Abbott FISH assay in the central lab.
Randomization will occur after ALK positive confirmation is received from the central
lab or local test using an method including Abbott FISH、RT-PCR or Ventana IHC.
7. No brain metastasis, or asymptomatic brain metastasis, or symptomatic brain metastasis
but stable for more than 4 weeks after treatment, and have stopped systemic hormone
treatment (prednisone of > 10 mg/day or equivalent hormone) for more than 2 weeks
8. Patients must have normal function as defined: ANC≥1.5*10^9/L; PLT≥90*10^9/L, Hb≥90
g/L, Total Bilirubin （TBIL）≤1.5*Upper Limit of Normal（ULN） ( Gilbert's Syndrome TBIL
≤3.0*ULN and DBIL≤1.5*ULN )，Alanine Transaminase （ALT）and Aspartate
Aminotransferase（AST）≤2.5*ULN. For liver metastasis patients, ALT and AST≤5*ULN,
Cr≤1.5*ULN, LVEF≥50%.
9. Any surgery or prior radiation (expect for palliative radiation) /operations must have
been completed at least 4 weeks prior to first dosing. Palliative radiation must have
been completed at least 48 hours prior to first dosing.
10. Patients must be able to understand and volunteer to sign the informed consent.
Exclusion Criteria:
1. Patients that have previously received cancer therapy (i.e., other targeted therapies,
chemotherapy, immunotherapy, biologic therapy, hormonal therapy).
2. Patients with tumor meningeal metastasis
3. Clinically significant cardiovascular disease within 6 months prior to first dosing.
4. Two consecutive corrected QT interval (QTc) > 480 ms through ECG examination during
screening, ≥2 arrhythmias, ≥2 heart failure (according to CTCAE 4.03), atrial
fibrillation and ventricular fibrillation of any grade, or clinically significant
supraventricular or ventricular arrhythmia requiring treatment or intervention
5. Patients need medications that may prolong QT interval or induce torsades de pointes
within 14 days prior to the first dosing or during the study.
6. Continuous use of corticosteroids for more than 30 days, or require chronic use of
corticosteroids or other immunosuppressants
7. Past history of a large area of diffuse/interstitial pulmonary fibrosis, or known
history of Grade 3 or 4 interstitial pulmonary fibrosis or interstitial lung disease.
8. Patients with Grade > 1 nausea, vomiting, or diarrhea (CTCAE 4.03), other GI
dysfunction or GI disease that may potentially affect drug absorption.
9. Patients at risk for GI perforation or intestinal obstruction
10. Patient has received other investigational drug within 1 month prior to first dosing.
Subject received other clinical trial treatment within 1 month prior to the first dose
of the investigational drug.
11. Patients who are HBsAg-positive and/or HBcAB positive and HBV DNA > 103copies/mL, or
HCV antibody-positive, or syphilis antibody- positive or known HIV infected.
12. Patients who cannot suspend the use of a strong CYP3A4 inducer or inhibitor at least 1
weeks prior to this study and during the study.
13. Patients who cannot suspend the use of a CYP3A4 substrate at least 1 weeks prior to
this study and during the study, and the therapeutic index is low.
14. Females who are pregnant or breastfeeding. Pregnant or lactating female patients or a
positive pregnancy test at baseline for females of childbearing potential.
15. Female patients who are unwilling to use effective contraceptive measures during the
entire course of the study and within 6 months after the end of the study, or male
patients who plan to have children.
16. Concurrent diseases that may seriously affect patient safety or impact patient
completion of the study as determined by the investigator (such as clinically
uncontrolled hypertension (blood pressure > 160/110 mmHg), severe diabetes, or thyroid
disease).
17. Drug abusers and alcoholics. Drug or alcohol abuse. Alcohol abuse refers to drinking
14 units of alcohol per week: 1 unit = 285mL of beer, or 25mL of spirits, or 100mL of
wine;
18. History of definitive neurological or mental disorder, including epilepsy or dementia
19. Patients with other malignant tumors within 5 years prior to screening (except for
cured basal cell carcinoma of the skin, cervical carcinoma in situ, thyroid carcinoma
in situ, and papillary thyroid carcinoma).
20. Patients with added risks associated with the study or may interfere with the
interpretation of study results as determined by the investigator, or deemed
unsuitable by the investigator and/or sponsor.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
, 0531-83129659, [email protected]
Location Countries
China
Location Countries
China
Administrative Informations
NCT ID
NCT04632758
Organization ID
WX0593-004
Responsible Party
Sponsor
Study Sponsor
Qilu Pharmaceutical Co., Ltd.
Study Sponsor
, ,
Verification Date
March 2020