Clinical Trial of WB100 on Advanced Solid Tumor

Solid Tumor Clinical Trial

Official title:

An Open, Dose Escalation, Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of WBC100 in Patients With Advanced Solid Tumor

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05100251
• Other study ID #: WBC100
• Status: Recruiting
• Phase: Phase 1
• Start date: October 25, 2021
• Est. completion date: October 25, 2023

Study information

• Verified date: January 2023
• Source: Zhejiang University
• Contact: Qi Zhang
• Phone: 13858108798
• Email: zhangqi[@]zju.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase I clinical study of WBC100 in Patients with advanced solid tumor.

Description:

This is a phase I open-label, single and dose escalation study to evaluate the safety, cell 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: October 25, 2023
• Est. primary completion date: October 25, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Sign informed consent, able to follow protocol requirements

2. Aged 18 to 75 years, male or female

3. Dose escalation stage: Histopathology or cytology proven advanced solid tumor with positive C-myc who have developed progressive disease or intolerability after at least one line of standard systemic therapies Dose expansion stage: Histopathology or cytology proven advanced pancreatic cancer with positive C-myc who are not suitable for surgery or local treatment, have developed progressive disease or intolerability after at least one line of standard systemic therapies Positive C-myc refer to C-myc overexpression: more than 10% tumor cells are detected 1+ by immunohistochemistry (IHC)

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 = upper limits of normal) 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 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

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

Drug:
• WBC100
The first stage: single dose escalation according to classic "3+3" dose escalation method. 6 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, 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 3 weeks and off for 1 week. The second stage: Two dose levels will be chosen according to data from the first stage. Each dose stage enroll 12 pancreatic patients with positive c-myc expression.

Locations

Country	Name	City	State
China	the First Affiliated Hospital, School of Medicine, Zhejiang University	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Zhejiang University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of Adverse Event and Severe Adverse Event	AEs and SAEs will be assessed by CTCAE v5.0	2 years
Primary	Dose limited toxicity(DLT)	safety	28 days
Primary	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
Secondary	Cmax	Peak plasma concentration after one dose	28 days
Secondary	Tmax	Time to peak plasma concentration after one dose	28 days
Secondary	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
Secondary	AUC0-inf	Area under the plasma concentration versus time curve;time range from 0 to infinity	28 days
Secondary	T1/2	half-life period	28 days
Secondary	?z	elimination rate constant	28 days
Secondary	CL/F	apparent clearance	28 days
Secondary	Vz/F	apparent volume of distribution	28 days
Secondary	Cmax, ss	Steady peak plasma concentration after multiple dose	28 days
Secondary	Cmin, ss	Steady minimal plasma concentration after multiple dose	28 days
Secondary	Cavg	Steady averagel plasma concentration after multiple dose	28 days
Secondary	Tmax, ss	Time to steady peak plasma concentration after multiple dose	28 days
Secondary	CLss/F	steady apparent clearance	28 days
Secondary	Vss/F	steady apparent volume of distribution	28 days
Secondary	ARCmax	Peak concerntration cumulative coefficient	28 days
Secondary	ARAUC	AUC cumulative coefficient	28 days
Secondary	DF	degree of fluctuation	28 days
Secondary	CA19-9	Change of CA19-9	28 days
Secondary	CA125	Change of CA125	28 days
Secondary	Serum ferritin	change of serum ferritin	28 days
Secondary	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
Secondary	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
Secondary	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
Secondary	change of tumor size	The major axis change of target lesion relative to baseline	52 weeks