A Study of PLB1001 Enteric Capsules in the Treatment of sGBM/IDH Mutant Glioblastoma Patients With the ZM Fusion Gene (FUGEN).
Study Details
Study Description
Brief 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:
-
To evaluate overall survival (OS) in the treatment of secondary glioblasts with positive recurrence of PTPRZ1-MET (ZM) fusion gene by PLB1001 Enteric Capsules.
-
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
-
Be given PLB1001 300mg BID,oral who were randomly assigned in test group.
-
Be given Temozolomide capsules ,oral, who were randomly assigned in control group.
-
Be given EP, ivgtt, who were randomly assigned in control group.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
Detailed 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).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: PLB1001 Subjects will receive 300mg of PLB1001 twice daily in cycles of 4 weeks duration until death or adverse event(AE) leading to discontinuation |
Drug: PLB1001
PLB1001 is a capsule in the form of 300mg,twice daily.
Other Names:
|
| Active Comparator: Temozolomide or Cisplatin combined with etoposide Investigators can choose one of two treatments Dose density of 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 |
Drug: Temozolomide
100-150mg/m2/d,day 1 to 7 and day 15 to 22 of each 28-day cycle
Drug: Cisplatin combined with Etoposide
Cisplatin:80-100mg/m2/3 days,28 days/cycle Etoposide:100mg/m2/d,3 days,28 days/cycle
|
Outcome Measures
Primary Outcome Measures
- Overall survival(OS) [5 years]
Overall survival is defined as the time(in months)from random to the date of death.
Secondary Outcome Measures
- Objective Response Rate Evaluated by Investigator(ORR) [5 years]
Objective response rate will be determined according to response assessment in neuro-oncology(RANO).
- Progression Free Survival evaluated by Investigator(PFS) [5 years]
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.
- Quality of Life Assessment EORTC-QLQ-C30 [5 years]
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.
- Karnofsky Performance Status score [5 years]
improved is defined as KPS increases >10 after treatment; worsen is defined as KPS decreases >10; stable is defined as KPS changes ≤10.
- Quality of Life Assessment EORTC-QLQ-BN20 [5 years]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
histologically confirmed secondary glioblastoma,or glioblastoma with IDH mutantation
-
Must have evidence of PRPRZ1-MET fusion gene positivity from the result of molecular pre-screening evaluations
-
Prior treatment with temozolomide and radiotherapy
-
Stable or decreasing dose of corticosteroids within 5 days prior to the first dose
-
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
-
Karnofsky performance score ≥ 60%
-
Pregnant or nursing women
-
Written consent
Exclusion Criteria:
-
Previous or current treatment with a c-Met inhibitor or HGF-targeting therapy
-
Received antibody anti-tumor drug within 30 days before enrollment
-
Previous treatment with Camustine sustained release implant
-
The subject is unable to undergo MRI scan
-
Patients with active bleeding were found by brain CT or MRI scan before enrollment
-
Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) 150 mm Hg and/or Diastolic Blood Pressure (DBP) ≥100 mm Hg
-
Major surgery within 4 weeks prior to first dose of PLB1001
-
Pregnant or nursing women
-
Involved in other clinical trials <30 days prior to first dose
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beijing Tiantan Hospital,Capital Medical University | Beijing | Beijing | China | 100070 |
Sponsors and Collaborators
- Beijing Pearl Biotechnology Limited Liability Company
Investigators
- Principal Investigator: Wenbin Li, Beijing Tiantan Hospital
- Principal Investigator: Xiaoguang Qiu, Beijing Tiantan Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PLB1001-Ⅱ-GBM-01