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A Study Evaluates the Safety, Pharmacokinetics and Efficacy of WX-0593 in Advanced Solid Tumor Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03389815
Recruitment Status : Recruiting
First Posted : January 4, 2018
Last Update Posted : January 4, 2018
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:
The purpose of the study is to evaluate safety, pharmacokinetics and efficacy of WX-0593 alone in the treatment of advanced cancer.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor, Non-small Cell Lung Cancer Drug: WX-0593 Tablets Phase 1 Phase 2

Detailed Description:
The first part is a single-arm, phase 1, open label, dose-escalation design in patients with anaplastic lymphoma kinase(ALK)/receptor tyrosine kinase(ROS1) Positive ALK/ROS1-positive solid tumor. The second part is an expansion in non-small cell lung Cancer (NSCLC) characterized by abnormalities in anaplastic lymphoma kinase(ALK) expression.

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Dose-escalation Study Followed by an Extension Phase Evaluating the Safety, Pharmacokinetics and Efficacy of WX-0593 in Advanced Solid Tumor Patients With Anaplastic Lymphoma Kinase(ALK)/Receptor Tyrosine Kinase(ROS1) Positive
Actual Study Start Date : September 14, 2017
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: WX-0593 Tablets
The first part is a dose-escalation design in patients with ALK/ROS1-positive solid tumor. The second part is an expansion in non-small cell lung Cancer (NSCLC) characterized by abnormalities in ALK expression.
Drug: WX-0593 Tablets
tablets, dosage ranged from 30 mg to 300 mg, quaque die(QD)
Other Name: FL-006


Outcome Measures

Primary Outcome Measures :
  1. Maximum tolerated dose(MTD) [ Time Frame: 28 days ]
    The MTD is determined by the number of the participants in cohort who suffer a dose-limiting toxicity (DLT). The MTD is defined as the former dose at which more than one third of the participants develop a DLT. If no DLTs are observed, the MTD is not reached.


Secondary Outcome Measures :
  1. Tmax of WX-0593 [ Time Frame: 28 days ]
    Pharmacokinetics of WX-0593 by assessment of time to Cmax

  2. Cmax of WX-0593 [ Time Frame: 28 days ]
    Pharmacokinetics of WX-0593 by assessment of maximum plasma WX-0593 concentration.

  3. Cmin of WX-0593 [ Time Frame: 28 days ]
    Pharmacokinetics of WX-0593 by assessment of minimum plasma WX-0593 concentration.

  4. AUC of WX-0593 [ Time Frame: 28 days ]
    Pharmacokinetics of WX-0593 by assessment of area under the plasma concentration time curve from zero to infinity

  5. tl/2 of WX-0593 [ Time Frame: 28 days ]
    Pharmacokinetics of WX-0593 by assessment of the terminal half-life

  6. Cssmin of WX-0593 [ Time Frame: 28 days ]
    Cmin of WX-0593 at steady state

  7. Cssmax of WX-0593 [ Time Frame: 28 days ]
    Cmax of WX-0593 at steady state

  8. Css-av of WX-0593 [ Time Frame: 28 days ]
    Mean plasma concentration of WX-0593 at steady state

  9. AUCss of WX-0593 [ Time Frame: 28 days ]
    area under the curve of WX-0593 at steady state

  10. DF of WX-0593 [ Time Frame: 28 days ]
    Pharmacokinetics of WX-0593 by assessment of degree of fluctuation

  11. Vz of WX-0593 [ Time Frame: 28 days ]
    volume of distribution during terminal phase after WX-0593 administration

  12. CLs of WX-0593 [ Time Frame: 28 days ]
    total plasma,serum or blood clearance of WX-0593 after administration

  13. Objective Response Rate (ORR) [ Time Frame: From fist administration of WX-0593 to 28 days after last medication. ]

    Primary efficacy endpoint is a change in the proportion of subjects showing overall objective response rate (ORR) from baseline to final tumor assessment point after treatment. As Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, the percentage of subjects indicating PR (partial response) and CR (complete response) will be calculated.

    According to RECIST 1.1 criteria, complete response (CR) - the disappearance of all target lesions and partial response ( PR ) - at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.


  14. Progression-free survival (PFS) [ Time Frame: From fist administration of WX-0593 to 28 days after last medication. ]
    PFS defined as the time from baseline to first observed disease progression or death from any cause.

  15. Disease Control Rate (DCR) [ Time Frame: From fist administration of WX-0593 to 28 days after last medication. ]

    DCR is the percentage of patients with best response of CR, PR or Stable Disease (SD).

    SD was defined as neither sufficient shrinkage to qualify for a PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of the longest diameter.


  16. Duration of Response (DOR) and so on [ Time Frame: From fist administration of WX-0593 to 28 days after last medication. ]
    The DOR is defined as the time from the date of the first response CR/PR (whichever is first recorded) to the date on which progressive disease (PD) is first noted or date of death.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 18 to 70 years, inclusive.
  2. Female or male
  3. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
  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 solid tumor malignancy with ALK/ROS1+ (For the expansion phase, patients must have NSCLC with ALK+ ):

    • Patients with advanced tumor (eg. NSCLC, lymphoma, inflammatory myofibroblastic tumor) who failed in standard treatment (eg. resistant of ALK inhibitors or chemotherapy)
    • Patients with advanced NSCLC who cannot accept chemotherapy or intolerance with chemotherapy.
    • Advanced NSCLC patients who could not afford ALK inhibitor treatment.
  7. Patients with treated or untreated asymptomatic Central Nervous System(CNS) metastases may be allowed to enroll.
  8. Patients must have normal function as defined: ANC≥1.5*10^9/L PLT≥100*10^9/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 radiation (expect for palliative radiation) 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. All related adverse events from previous anti-cancer therapies must have recovered to ≤ Grade 1 (except for alopecia).
  11. Patients must be able to understand and volunteer to sign the informed consent.

Exclusion Criteria:

  1. Clinically significant cardiovascular disease within 3 months prior to first dosing.
  2. Ongoing cardiac dysrhythmias, or any grade of uncontrolled atrial fibrillation, or prolonged QT interval (QTc > 480 ms).
  3. 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.
  4. Peripheral neuropathy ≥ Grade 3 according to CTCAE 4.03.
  5. Patients who received continuous use of steroids for more than 30 days, or who need long-term use of steroid hormones or other immunosuppressive agents.
  6. History of extensive disseminated/bilateral pulmonary interstitial fibrosis, interstitial fibrosis or interstitial lung disease of Grade 3/4 .
  7. Presence of active gastrointestinal (GI) disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of WX-0593.
  8. Patients who are receiving warfarin sodium (Coumadin) or any other coumadin-derived anticoagulants,and patients with coagulation disturbance and bleeding tendency.
  9. Patient has received other investigational drug within 1 month.
  10. Patients with acute or chronic infectious medical conditions, including active hepatitis (Hepatitis A、 Hepatitis B、 Hepatitis C ) or HIV infection.
  11. Patients who received prior anti-cancer therapy within 2 weeks (t1/2 ≤ 3 days) or within 4 weeks (3 days < t1/2). Patients previously treated with crizotinib could start WX-0593 dosing after 1 week from the last dosing.
  12. Patients who could not discontinue therapy with potent CYP3A4 inhibitors or inducers within 1 week prior first dosing, or patients who need therapy with CYP3A4 inhibitors or inducers during the study.
  13. Patients received medications known to be metabolized by CYP3A4 and with narrow therapeutic indices, who could not discontinue within 1 week prior to the start of WX-0593 administration. Patients who need therapy with those medications during the study.
  14. Females who are pregnant or breastfeeding.
  15. Patients with childbearing potential must agree to use adequate contraception for the duration of treatment and for 6 months after the study.
  16. Drug abusers and alcoholics.
  17. History of definite nerves or psychosis diseases including epilepsy or dementia.
  18. History of other malignancy.
  19. Concurrent condition that in the investigator's opinion would jeopardize compliance with the protocol or would impart excessive risk associated with study participation that would make it inappropriate for the patient to be enrolled.
Contacts and Locations

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): NCT03389815


Locations
China, Beijing
Cancer Institute and Hospital, Chinese Academy of Medical Sciences Recruiting
Beijing, Beijing, China, 100021
Contact: Yuankai Shi, M.D.    86-010-87788293    syuankaipumc@126.com   
Sponsors and Collaborators
Qilu Pharmaceutical Co., Ltd.
Investigators
Principal Investigator: Yuankai Shi, M.D. Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Principal Investigator: Jian Fang, M.D. Beijing Cancer Hospital
Principal Investigator: Shucai Zhang, M.D. Beijing Chest Hospital, Capital Medical University
Principal Investigator: Yunpeng Liu, M.D. First Hospital of China Medical University
More Information

Responsible Party: Qilu Pharmaceutical Co., Ltd.
ClinicalTrials.gov Identifier: NCT03389815     History of Changes
Other Study ID Numbers: WX0593-001
First Posted: January 4, 2018    Key Record Dates
Last Update Posted: January 4, 2018
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

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