A Study of PLB1001 Enteric Capsules in the Treatment of sGBM/IDH Mutant Glioblastoma Patients With the ZM Fusion Gene (FUGEN).

Glioblastoma Clinical Trial

Official title:

A Randomized, Controlled, Open, Multicenter, Phase II/III Clinical Study to Evaluate the Safety and Efficacy of Vebreltinib Enteric Capsules in the Treatment of sGBM/IDH Mutant Glioblastoma Patients With the ZM Fusion Gene (FUGEN).

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06105619
• Other study ID #: PLB1001-?-GBM-01
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: October 8, 2018
• Est. completion date: December 31, 2024

Study information

• Verified date: October 2023
• Source: Beijing Pearl Biotechnology Limited Liability Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to evaluate the safety and efficacy of PLB1001 Enteric Capsules in the treatment of PTPRZ1-MET fusion gene positive recurrent secondary glioblastoma. The main questions it aims to answer are:

1. To evaluate overall survival (OS) in the treatment of secondary glioblasts with positive recurrence of PTPRZ1-MET (ZM) fusion gene by PLB1001 Enteric Capsules.

2. To evaluate if it is safety and tolerant in the treatment of secondary glioblasts with positive recurrence of PTPRZ1-MET (ZM) fusion gene by PLB1001 Enteric Capsules.

Participants will

1. Be given PLB1001 300mg BID,oral who were randomly assigned in test group.

2. Be given Temozolomide capsules ,oral, who were randomly assigned in control group.

3. Be given EP, ivgtt, who were randomly assigned in control group.

Description:

84 sGBM or IDH mutant glioblastoma patients with the ZM fusion gene will be randomly divided into group A (receive vebreltinib) or group B ( receive investigator choose), and the randomize ratio will be 1:1, patients in group A will receive PLB1001 300mg Bid, 28days/cycle. Patients in group B will receive temozolomide (100-150mg/m2/d, 7 days 1 to7 and days 15 to 22 of each 28-day cycle ) or cisplatin+etoposide(cisplatin:80-100mg/m2/3 days, 28days/cycle; etoposide:100mg/m2/d, 3days, 28 days/cycle).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 84
• Est. completion date: December 31, 2024
• Est. primary completion date: April 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. histologically confirmed secondary glioblastoma,or glioblastoma with IDH mutantation

2. Must have evidence of PRPRZ1-MET fusion gene positivity from the result of molecular pre-screening evaluations

3. Prior treatment with temozolomide and radiotherapy

4. Stable or decreasing dose of corticosteroids within 5 days prior to the first dose

5. Platelet count=75×109/L,Neutrophilic granulocyte count=1.5×109/L, Hemoglobin>90g/L,AST or ALT < 3 times the lab's upper normal limit,Serum creatinine < 1.5 times the lab's upper normal limit,INR=2.0

6. Karnofsky performance score = 60%

7. Pregnant or nursing women

8. Written consent

Exclusion Criteria:

1. Previous or current treatment with a c-Met inhibitor or HGF-targeting therapy

2. Received antibody anti-tumor drug within 30 days before enrollment

3. Previous treatment with Camustine sustained release implant

4. The subject is unable to undergo MRI scan

5. Patients with active bleeding were found by brain CT or MRI scan before enrollment

6. Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) 150 mm Hg and/or Diastolic Blood Pressure (DBP) =100 mm Hg

7. Major surgery within 4 weeks prior to first dose of PLB1001

8. Pregnant or nursing women

9. Involved in other clinical trials <30 days prior to first dose

Related Conditions & MeSH terms

• Glioblastoma

Intervention

Drug:
• PLB1001
PLB1001 is a capsule in the form of 300mg,twice daily.
• Temozolomide
100-150mg/m2/d,day 1 to 7 and day 15 to 22 of each 28-day cycle
• Cisplatin combined with Etoposide
Cisplatin:80-100mg/m2/3 days,28 days/cycle Etoposide:100mg/m2/d,3 days,28 days/cycle

Locations

Country	Name	City	State
China	Beijing Tiantan Hospital,Capital Medical University	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Pearl Biotechnology Limited Liability Company

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival(OS)	Overall survival is defined as the time(in months)from random to the date of death.	5 years
Secondary	Objective Response Rate Evaluated by Investigator(ORR)	Objective response rate will be determined according to response assessment in neuro-oncology(RANO).	5 years
Secondary	Progression Free Survival evaluated by Investigator(PFS)	Progression Free Survival is defined as the time (in months) from the first administration of trial treatment to the date of the first documentation of PD or death due to any cause.	5 years
Secondary	Quality of Life Assessment EORTC-QLQ-C30	The EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item scales and single-item measures. These include the Physical Functioning Scale and four more functional scales (role, emotional, social, and cognitive), three symptom scales (fatigue, nausea and vomiting, and pain), a global health status / QoL scale, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and difficulties). Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." The method for scoring these scales is: 1. Estimate the average of the items that contribute to the scale; this is the raw score. 2. Use a linear transformation to standardize the raw score, so that scores range from 0 to 100; a higher score represents a higher ("better") level of functioning, or a higher ("worse") level of symptoms. A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.	5 years
Secondary	Karnofsky Performance Status score	improved is defined as KPS increases >10 after treatment; worsen is defined as KPS decreases >10; stable is defined as KPS changes =10.	5 years
Secondary	Quality of Life Assessment EORTC-QLQ-BN20	The EORTC-QLQ-BN20 covers future uncertainty, visual disorder, motor dysfunction, communication deficit, headache, seizures, drowsiness, hair loss, itching, difficulty with bladder control, and weakness of both legs. Patients respond by self-report, with most items rated on a 4-point scale, from 1 "not at all" to 4 "very much", except for the two global health status/quality of life items, which are measured on a 7-point Likert scale ("very poor" through "excellent"). The method for scoring these scales is: 1. Estimate the average of the items that contribute to the scale; this is the raw score. 2. Use a linear transformation to standardize the raw score, so that scores range from 0 to 100; a higher score represents a higher ("better") level of functioning, or a higher ("worse") level of symptoms. A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.	5 years