Clinical Trial of WBC100 on Advanced Solid Tumor

NCT ID: NCT05100251

Last Updated: 2024-12-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-25
• Study Completion Date: 2025-10-25

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, single and 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.

Conditions

Solid Tumor

Keywords

C-myc; Solid tumor

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Once every other day (QOD)

(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

Group Type: EXPERIMENTAL

WBC100 QOD

Intervention Type: DRUG

The first stage: single dose escalation according to classic "3+3" dose escalation method. 7 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. 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 will enroll 12 c-myc-positive patients with a selected cancer type

Twice daily (BID)

(2) Twice daily (BID): dosing for 2 consecutive weeks, followed by a 1-week rest period, with 3 weeks as one treatment cycle;

Group Type: EXPERIMENTAL

WBC100 BID

Intervention Type: DRUG

The first stage: 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. 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; The second stage: Two dose levels will be chosen according to data from the first stage. Each dose stage will enroll 12 c-myc-positive patients with a selected cancer type

Once daily (QD)

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

Group Type: EXPERIMENTAL

WBC100 QD

Intervention Type: DRUG

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, 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. The second stage: Two dose levels will be chosen according to data from the first stage. Each dose stage will enroll 12 c-myc-positive patients with a selected cancer type

Interventions

WBC100 QOD

The first stage: single dose escalation according to classic "3+3" dose escalation method. 7 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. 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 will enroll 12 c-myc-positive patients with a selected cancer type

Intervention Type: DRUG

WBC100 QD

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, 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. The second stage: Two dose levels will be chosen according to data from the first stage. Each dose stage will enroll 12 c-myc-positive patients with a selected cancer type

Intervention Type: DRUG

WBC100 BID

The first stage: 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. 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; The second stage: Two dose levels will be chosen according to data from the first stage. Each dose stage will enroll 12 c-myc-positive patients with a selected cancer type

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

TingBo Liang

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tingbo Liang

Role: PRINCIPAL_INVESTIGATOR

Zhejiang University

Locations

the First Affiliated Hospital, School of Medicine, Zhejiang University

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Qi Zhang

Role: CONTACT

Phone: 13858108798

Email: zhangqi@zju.edu.cn

Qihan Fu

Role: CONTACT

Email: ayfuqihan@126.com

Facility Contacts

TingBo Liang, MD, PHD

Role: primary

Other Identifiers

WBC100

Identifier Type: -

Identifier Source: org_study_id