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sponsor's decision to change development strategy (the QOD cohort was completed).
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| Name | Class |
|---|---|
| Hangzhou Weben Pharma Co., Ltd | INDUSTRY |
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This is a phase I clinical study of WBC100 in patients with advanced solid tumor.
This is a phase I open-label, dose escalation study to evaluate the safety, pharmacokinetics, and preliminary efficacy of WBC100, a drug targeting c-myc, in subjects who have been diagnosed with c-myc positive advanced solid tumor and refractory or intolerant to current standard systemic treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Once every other day (QOD) | Experimental | (1) Once every other day (QOD): after a single-dose administration (C0) and 2-day washout period, subjects will start receiving multiple doses, for 2 consecutive weeks, followed by a 1-week rest period, with 3 weeks as one treatment cycle |
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| Twice daily (BID) | Experimental | (2) Twice daily (BID): dosing for 2 consecutive weeks, followed by a 1-week rest period, with 3 weeks as one treatment cycle; |
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| Once daily (QD) | Experimental | Once daily (QD): dosing 3 consecutive weeks (with QD dosing for the first 5 days of each week followed by a 2-day rest), followed by a 1-week rest period, with a 4 weeks as one cycle |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| WBC100 QOD | Drug | The first stage: single dose escalation according to classic "3+3" dose escalation method. 9 increasing dose levels were set up, with 3 to 6 cases per dose. The first dose group is 0.5 mg QOD. The second dose group is 1mg QOD. The third dose group is 1.5 mg QOD. The fourth dose group is 2.0 mg QOD. The fifth dose group is 2.5 mg QOD. The sixth dose group is 3.0 mg QOD. The seven dose group is 3.5 mg QOD. The 8th dose group is 4.0 mg QOD. The 9th dose group is 4.5 mg QOD. In each dose group, patients take WBC100 once on cycle 0. After a washout period of 2 days, patents start subsequent 4 weeks cycles until progression disease or intolerable toxicity. In each cycle, patient was on WBC100 every for 2 weeks and off for 1 week. The second stage: One dose levels was chosen according to data from the first stage. 16 c-myc-positive patients with pancreatic cancer was enrolled |
| Measure | Description | Time Frame |
|---|---|---|
| Frequency of Adverse Event and Severe Adverse Event | AEs and SAEs will be assessed by CTCAE v5.0 | 2 years |
| Dose limited toxicity(DLT) | safety | 28 days |
| Maximum Tolerated Dose(MTD) | The highest dose level at which < 2 of 6 subjects experienced a dose limiting toxicity during the first 28 days of the treatment period | 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax | Peak plasma concentration after one dose | 28 days |
| Tmax | Time to peak plasma concentration after one dose | 28 days |
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Inclusion Criteria:
Sign informed consent, able to follow protocol requirements;
Aged 18 to 75 years, male or female
(1)Dose escalation stage: Histopathology or cytology proven patients with advanced solid tumor with positive C-myc expression who have developed progressive disease or intolerability after at least one line of standard systemic therapies.(2)Dose expansion stage: Histopathology or cytology proven patients with advanced solid tumor of a selected cancer type with positive C-myc expression who have developed progressive disease or intolerability after at least one line of standard systemic therapies. Positive C-myc refers to more than 1% tumor cells are detected 1+ by immunohistochemistry (IHC) in histologic section.
ECOG Performance Status score: 0 to 2 points
Expected survival is > 3 months
Adequate hematologic and organ functions (without persistent supportive treatment)
f. Left ventricular ejection fraction (LVEF) ≥ 50%. Heart rate (HR) ≥ 60 bpm. QT intervals, male ≤ 450 ms, female ≤ 470 ms
According to RECIST 1.1, patients have at least one evaluable target lesion(only for dose expansion stage)
Female patients of child-bearing potential or male subjects whose spouses are women of childbearing potential must agree to use a reliable method of contraception (IUD, oral contraceptive, condom) throughout the treatment period and for 3 months after discontinuation of WBC100. Female patients of child-bearing age must undergo a serum pregnancy test before the initiation of the study and the result must be negative.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Tingbo Liang | Zhejiang University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| the First Affiliated Hospital, School of Medicine, Zhejiang University | Hangzhou | Zhejiang | 310003 | China |
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| WBC100 QD | Drug | Single dose escalation according to classic "3+3" dose escalation method. 5 increasing dose levels were set up, with 3 to 6 cases per dose. The first dose group is 1.0 mg QD. The second dose group is 1.5 mg QD. The third dose group is 2.0 mg QD. The fourth dose group is 2.5 mg QD. The fifth dose group is 3.0 mg QD. In each dose group, the patient was on WBC100 until progression disease or intolerable toxicity. Patient was on WBC100 every for for 3 consecutive weeks (with QD dosing for the first 5 days of each week followed by a 2-day rest), followed by a 1-week rest period, with a 4 weeks as one cycle. |
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| WBC100 BID | Drug | Single dose escalation according to classic "3+3" dose escalation method. 4 increasing dose levels were set up, with 3 to 6 cases per dose. The first dose group is 0.5 mg QD. The second dose group is 1mg QD. The third dose group is 1.5 mg QD. The fourth dose group is 2.0 mg QD. The fifth dose group is 2.5 mg QD. The sixth dose group is 3.0 mg QD. In each dose group, the patient was on WBC100 until progression disease or intolerable toxicity. Patient was on WBC100 every for 2 consecutive weeks, followed by a 1-week rest period, with 3 weeks as one treatment cycle. |
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| AUC0-t | Area under the plasma concentration versus time curve after one dose and multiple dose;time range from 0 to last point when plasma concentration is detectable | 28 days |
| AUC0-inf | Area under the plasma concentration versus time curve;time range from 0 to infinity | 28 days |
| T1/2 | half-life period | 28 days |
| λz | elimination rate constant | 28 days |
| CL/F | apparent clearance | 28 days |
| Vz/F | apparent volume of distribution | 28 days |
| Cmax, ss | Steady peak plasma concentration after multiple dose | 28 days |
| Cmin, ss | Steady minimal plasma concentration after multiple dose | 28 days |
| Cavg | Steady averagel plasma concentration after multiple dose | 28 days |
| Tmax, ss | Time to steady peak plasma concentration after multiple dose | 28 days |
| CLss/F | steady apparent clearance | 28 days |
| Vss/F | steady apparent volume of distribution | 28 days |
| ARCmax | Peak concerntration cumulative coefficient | 28 days |
| ARAUC | AUC cumulative coefficient | 28 days |
| DF | degree of fluctuation | 28 days |
| CA19-9 | Change of CA19-9 | 28 days |
| CA125 | Change of CA125 | 28 days |
| Serum ferritin | change of serum ferritin | 28 days |
| Progression-free survival (PFS) | The period from the day when the subject receives the first study treatment to the first recorded tumor progression (whether treated or not) or death of any cause, which occurs first | 2 years |
| Duration of response (DOR) | The period from the first evaluation of complete response ( CR) or partial response (PR) to the first evaluation of progressive disease (PD)or death of any cause | 2 years |
| Objective response rate (ORR) | The number of cases in which tumor size is reduced to partial response (PR) or complete response (CR) / the total number of evaluable cases (%). In the event of partial response( PR) or complete response (CR), the subjects should confirm it no less than 4 weeks after the first evaluation | 2 years |
| change of tumor size | The major axis change of target lesion relative to baseline | 52 weeks |