A Study Evaluates the Safety and Efficacy of WX-0593 in ALK -Positive, or ROS1-positive Non-small Cell Lung Cancer
Phase II Clinical Study to Evaluate the Efficacy and Safety of WX-0593 in Patients With Crizotinib-resistant ALK -Positive, or Crizotinib-resistant/Crizotinib-naive ROS1-positive Non-small Cell Lung Cancer (NSCLC)
1 other identifier
interventional
176
1 country
41
Brief Summary
The purpose of the study is to evaluate safety and efficacy of WX-0593 oral tablets in ALK -positive, or ROS1-positive non-small cell lung cancer (NSCLC)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 nonsmall-cell-lung-cancer
Started Mar 2019
Shorter than P25 for phase_2 nonsmall-cell-lung-cancer
41 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 7, 2019
CompletedFirst Submitted
Initial submission to the registry
November 11, 2020
CompletedFirst Posted
Study publicly available on registry
November 24, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2021
CompletedNovember 24, 2020
November 1, 2020
1.7 years
November 11, 2020
November 17, 2020
Conditions
Outcome Measures
Primary Outcomes (1)
Confirmed Objective Response Rate (ORR) Assessed By An Independent Review Committee
ORR is defined the percentage of the participants who are confirmed to have achieved complete response (CR) or partial response (PR) per an Independent Review Committee (IRC) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 after the initiation of study treatment.
From frist administration of WX-0593 to the date that the last patients observed for 18 weeks.
Secondary Outcomes (9)
Confirmed Objective Response Rate (ORR) Assessed By Investigators
From frist administration of WX-0593 to the date that the last patients observed for 18 weeks.
Progression-free survival (PFS)
From frist administration of WX-0593 until firstly recorded disease progression or death (whichever occurs earlier), or to the date that the last patients observed for 18 weeks.
Disease Control Rate (DCR)
From frist administration of WX-0593 to the date that the last patients observed for 18 weeks.
Duration of Response (DOR)
From frist administration of WX-0593 to the date that the last patients observed for 18 weeks .
Time to Progression (TTP)
From frist administration of WX-0593 to the date that the last patients observed for 18 weeks.
- +4 more secondary outcomes
Study Arms (1)
WX-0593 Tablets
EXPERIMENTAL60 mg of WX-0593 tablets, once daily for 7 days, followed by 180 mg of WX-0593 tablets, once daily in a 21-days cycle.
Interventions
Eligibility Criteria
You may qualify if:
- ≥18 years.
- Female or male;
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
- Expected survival no less than 12 weeks.
- Patient should have at least one measurable lesion (RECIST 1.1); Lesions previously treated with radiotherapy can be considered target lesions only if there is a clear evidence of progression after radiotherapy.
- Histologically or cytologically confirmed advanced ALK-positive NSCLC in upper first-class hospitals，or histologically or cytologically confirmed advanced ROS1-positive NSCLC in a central laboratory. Admission of ROS1-positive patients will be based on the positive test results confirmed by the central laboratory or by the local-approved method.
- Patients with ALK-positive NSCLC who had been progressive disease after at least 12 weeks of continuous treatment with crizotinib .
- Patients with ROS1-positive NSCLC who failed in standard treatment (eg.resistant /intolerance of crizotinib or chemotherapy).
- Patients with ROS1-positive NSCLC who cannot accept chemotherapy.
- ROS1-positive NSCLC patients who could not afford crizotinib treatment.
- Patients with or without asymptomatic CNS metastases, or symptomatic brain metastasis after treatment stabilized for more than 4 weeks, and with stopping systemic sex hormone therapy for more than 2 weeks.
- Organ functions should meet the following requirements (Blood components, cell growth factors, drugs that stimulate the growth of WBC or platelets, or drugs used to correct anemia are not permitted within 14 days prior to the laboratory examination): 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%.
- Any surgery, prior radiotherapy (except for palliative radiotherapy)/procedures must be completed at least 4 weeks prior to starting the treatment with study drug. Palliative radiotherapy must be completed within 48 hours prior to starting treatment.
- Subject understands and voluntarily provides informed consent.
You may not qualify if:
- Received any prior ALK inhibitors other than crizotinib.
- Patients with brain meningeal metastasis.
- Any clinically significant cardiovascular disease within 6 months prior to the first dose of the investigational drug, including but not limited to: myocardial infarction, severe/unstable angina, coronary artery/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident (including transient ischemic attack).
- Two consecutive corrected QT interval (QTc) \> 480 ms through ECG examination during screening, patients with NCI-CTCAE v4.03 Grade ≥2 arrhythmia, Grade ≥2 heart failure, atrial fibrillation and ventricular fibrillation of any grade, or clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention.
- Concomitant use of medications that may cause QTc prolongation or induce Torsades de pointes within 14 days prior to the first dose of the investigational drug or during treatment.
- Continuous use of corticosteroids for more than 30 days, or require chronic use of corticosteroids or other immunosuppressants.
- 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, including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonitis, interstitial lung disease, obliterative bronchiolitis, or pulmonary fibrosis, but does not include local radiation pneumonitis or radiation-induced pulmonary fibrosis.
- Patients with Grade \> 1 nausea, vomiting, or diarrhea (CTCAE 4.03), other GI dysfunction or GI disease that may potentially affect drug absorption (such as ulcerative disease or malabsorption syndrome).
- Patients who are HBsAg-positive and/or HBcAb positive and HBV DNA \>10\^3 copies/mL, or HCV antibody-positive, or syphilis antibody- positive or known HIV infected.
- No more than 2 weeks between the most recent use of another anti-cancer treatment (half life ≤3 days) and the first dose of the investigational drug, or the most recent use of another anti-cancer treatment (half life \> 3 days) is less than 4 weeks. Patients previously treated with crizotinib could take WX-0593 tables after 1 week from the last dose.
- 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. These drugs include but are not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampicin, rifapentine, tipranavir, ritonavir, St. John's wart, and ketoconazole.
- 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.
- Pregnant or lactating female patients or a positive pregnancy test at baseline for females of childbearing potential.
- Childbearing potential 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.
- 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).
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (41)
The First Affiliated Hospital of Anhui Medical University
Hefei, Anhui, 230022, China
Oncology Department, Anhui Cancer Hospital
Hefei, Anhui, 233004, China
Respiratory Department, Anhui Cancer Hospital
Hefei, Anhui, 233004, China
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, 100021, China
Chinese PLA General Hospital
Beijing, Beijing Municipality, 100039, China
Thoracic Oncology I Department, Beijing Cancer Hospital
Beijing, Beijing Municipality, 100142, China
Thoracic Oncology II Department, Beijing Cancer Hospital
Beijing, Beijing Municipality, 100142, China
Peking Union Medical College Hospital
Beijing, Beijing Municipality, 100730, China
Beijing Chest Hospital
Beijing, Beijing Municipality, 101149, China
General Department, Beijing Chest Hospital, Capital Medical University
Beijing, Beijing Municipality, 101149, China
Army Medical Center of PLA
Chongqing, Chongqing Municipality, 400042, China
Fujian Cancer Hospital
Fuzhou, Fujian, 350014, China
Gansu Cancer Hospital
Lanzhou, Gansu, 620100, China
Cancer Center of Guangzhou Medical University
Guangzhou, Guangdong, 510095, China
Liuzhou People's Hospital
Liuchow, Guangxi, 545006, China
The Fourth Hospital of Hebei Medical University
Shijiangzhuang, Hebei, 050019, China
Harbin Medical University Cancer Hospital
Harbin, Heilongjiang, 150000, China
Henan Cancer Hospital
Zhengzhou, Henan, 450008, China
Hubei Cancer Hospital
Wuhan, Hubei, 430070, China
Hunan Tumor Hospital
Changsha, Hunan, 410006, China
The Affiliated Hospital of Inner Mongolia Medical University
Hohhot, Inner Mongolia, 010000, China
Nanjing Chest Hospital
Nanjing, Jiangsu, 210029, China
The First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, 215006, China
The Affiliated Hospital of Jiangnan University
Wuxi, Jiangsu, 214062, China
Xuzhou Central Hospital
Xuzhou, Jiangsu, 221009, China
The First Hospital of Jilin University
Changchun, Jilin, 130021, China
Jilin Cancer Hospital
Changchun, Jilin, 132000, China
The First Hospital of China Medical University
Shenyang, Liaoning, 110001, China
Qilu Hospital of Shandong University
Jinan, Shandong, 250012, China
Jinan Central Hospital
Jinan, Shandong, 250013, China
Shandong Cancer Hospital
Jinan, Shandong, 250117, China
The Affiliated Hospital of Qingdao University
Qingdao, Shandong, 266555, China
Yantai Yuhuangding Hospital
Yantai, Shandong, 264000, China
Shanxi Cancer Hospital
Taiyuan, Shanxi, 030013, China
Tangdu Hospital
Xi’an, Shanxi, 710038, China
Affiliated Hospital of North Sichuan Medical College
Nanchong, Sichuan, 637000, China
Tianjin Cancer Hospital
Tianjin, Tianjin Municipality, 300060, China
Cancer Hospital Affiliated to Xinjiang Medical University
Ürümqi, Xinjiang, 830011, China
Yunnan Cancer Hospital
Kunming, Yunnan, 650100, China
Hangzhou first people's Hospital
Hangzhou, Zhejiang, 310006, China
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, 310022, China
Related Publications (1)
Shi Y, Chen J, Zhang H, Zhang Z, Zhang Y, Wang Z, Zhang S, Zhao J, Liu C, Wang X, Zhao Y, Hu C, Yang L, Hao X, Wang L, Liu Y, Yu Y, Zhao J, Wang M, Zhang L, Sun S, Hu Y, Gu K, Hang X, Shan J, Zhang Y, Tan B, Yang W, Yang R, Si M, Geng H, Li H, Kang X. Efficacy and safety of iruplinalkib (WX-0593) in ALK-positive crizotinib-resistant advanced non-small cell lung cancer patients: a single-arm, multicenter phase II study (INTELLECT). BMC Med. 2023 Feb 24;21(1):72. doi: 10.1186/s12916-023-02738-5.
PMID: 36829154DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 11, 2020
First Posted
November 24, 2020
Study Start
March 7, 2019
Primary Completion
December 1, 2020
Study Completion
March 1, 2021
Last Updated
November 24, 2020
Record last verified: 2020-11