Solid Tumor
Conditions
Keywords
C-myc, Solid tumor
Brief summary
This is a phase I clinical study of WBC100 in patients with advanced solid tumor.
Detailed description
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.
Interventions
DRUGWBC100 QOD
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
DRUGWBC100 QD
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.
DRUGWBC100 BID
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.
Sponsors
Zhejiang University
Hangzhou Weben Pharma Co., Ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Sign informed consent, able to follow protocol requirements； 2. Aged 18 to 75 years, male or female 3. （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. 4. ECOG Performance Status score: 0 to 2 points 5. Expected survival is \> 3 months 6. Adequate hematologic and organ functions (without persistent supportive treatment) 1. Absolute Neutrophil Count \> 1.5 × 109/L, Platelet count ≥ 75 × 109/L, Hemoglobin \> 8.5 g/dL 2. INR and PT ≤ 2 × ULN 3. ALB \> 3.0 g/dL, Bilirubin level ≤ 2 × ULN, AST and ALT ≤ 2 × ULN or \< 5 × ULN in the presence of liver metastases 4. Calculated creatinine clearance (e.g. Cockcroft-Gault) ≥ 60 ml/min or serum creatinine ≤ 1.5 × ULN f. Left ventricular ejection fraction (LVEF) ≥ 50%. Heart rate (HR) ≥ 60 bpm. QT intervals, male ≤ 450 ms, female ≤ 470 ms 7. According to RECIST 1.1, patients have at least one evaluable target lesion(only for dose expansion stage) 8. 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
1. Allergic to WBC100 or its excipients or with allergic constitution 2. Major surgery, active ulcer or unhealing wound occurred within 4 weeks before first dose 3. Taken drugs in other clinical trials within 4 weeks or still in the safety follow-up period 4. Subjects have Spinal compression, brain metastases and meningeal metastases (subjects who is asymptomatic, stable or with no need for steroid for at least 4 weeks before first dose are allowed) 5. Subjects have history of cardiac insufficiency (NYHA III-IV) or uncontrolled congestive heart failure (NYHA II-IV) within 6 months before consent 6. Subjects have risk factors of QT intervals prolongation or arrhythmia, such as Idiopathic Q-T interval prolongation syndrome or history of drug induced arrhythmia 7. Subject have any condition within 6 months before consent: unstable angina pectoris requiring surgical intervention, uncontrolled hypertension (systolic pressure ≥ 140 mmHg, diastolic pressure ≥ 90 mmHg), myocardial infarction, stroke (lacunar infarction is allowed), Coronary/peripheral artery bypass surgery, pulmonary embolism 8. Infection of HIV, active infection of HBV (HBV DNA \> 1000 IU/ml) active infection of HC (HCV-RNA ≥ upper limits of normal) 9. History of severe infection within 28 days before enrolled, including uncontrolled infection requiring systemic treatment of bacteria, virus and fungus 10. The side effects caused by the previous treatment of the subjects did not return to grade ≤1 according to CTCAE 5.0 with exception of tolerable events determined by investigator such as hair loss and grade 2 Peripheral neuropathy 11. Subjects with uncontrolled nausea or vomiting, chronic gastrointestinal diseases, unable to swallow pills, enterostomy, uncontrolled diarrhea or any intestinal surgery that cause insufficient absorption of WBC100 12. Subjects taking any strong CYP inducers or inhibitors or Chinese medicine within 7 days prior to the first dose of study drug 13. History of malignancy in the last 2 years with the exception of patients with prior history of in situ breast cancer, in situ cervical cancer, basal or squamous cell skin cancer who have already been cured 14. Subjects who have antitumor therapy within 28 days prior to first dose of WBC100, such as monoclonal antibody, chemotherapy, radiotherapy and Chinese medicine 15. Subjects have mental disorders or history of drug abuse that may limit subjects' participation in this trial 16. Unable to tolerate intravenous blood collection 17. According to the investigators' evaluation, patients are unable or unwilling to comply with the requirements of the study protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Adverse Event and Severe Adverse Event | 2 years | AEs and SAEs will be assessed by CTCAE v5.0 |
| Dose limited toxicity（DLT） | 28 days | safety |
| Maximum Tolerated Dose（MTD） | 28 days | The highest dose level at which \< 2 of 6 subjects experienced a dose limiting toxicity during the first 28 days of the treatment period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | 28 days | Peak plasma concentration after one dose |
| Tmax | 28 days | Time to peak plasma concentration after one dose |
| AUC0-t | 28 days | 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 |
| AUC0-inf | 28 days | Area under the plasma concentration versus time curve；time range from 0 to infinity |
| T1/2 | 28 days | half-life period |
| λz | 28 days | elimination rate constant |
| CL/F | 28 days | apparent clearance |
| Vz/F | 28 days | apparent volume of distribution |
| Cmax, ss | 28 days | Steady peak plasma concentration after multiple dose |
| Cmin, ss | 28 days | Steady minimal plasma concentration after multiple dose |
| Cavg | 28 days | Steady averagel plasma concentration after multiple dose |
| Tmax, ss | 28 days | Time to steady peak plasma concentration after multiple dose |
| CLss/F | 28 days | steady apparent clearance |
| Vss/F | 28 days | steady apparent volume of distribution |
| ARCmax | 28 days | Peak concerntration cumulative coefficient |
| ARAUC | 28 days | AUC cumulative coefficient |
| DF | 28 days | degree of fluctuation |
| CA19-9 | 28 days | Change of CA19-9 |
| CA125 | 28 days | Change of CA125 |
| Serum ferritin | 28 days | change of serum ferritin |
| Progression-free survival (PFS) | 2 years | 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 |
| Duration of response (DOR) | 2 years | 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 |
| Objective response rate (ORR) | 2 years | 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 |
| change of tumor size | 52 weeks | The major axis change of target lesion relative to baseline |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORTingbo Liang
Zhejiang University
Outcome results
None listed