Study of a c-Met Inhibitor PLB1001 in Patients With PTPRZ1-MET Fusion Gene Positive Recurrent High-grade Gliomas

Glioma Clinical Trial

Official title:

A Phase I, Open-label, Dose Escalation Study to Assess the Safety, Tolerability and Pharmacokinetics (PK) of PLB1001 in Patients With PTPRZ1-MET Fusion Gene Positive Recurrent High-grade Gliomas

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02978261
• Other study ID #: HMO-PLB1001-I-GBM-01
• Status: Completed
• Phase: Phase 1
• Start date: September 2016
• Est. completion date: December 2018

Study information

• Verified date: August 2018
• Source: Beijing Pearl Biotechnology Limited Liability Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase I, open-label, dose-escalation study was conducted to determine the maximum tolerated dose (MTD), recommended phase II dose (RP2D), dose-limiting toxicities (DLTs), pharmacokinetics (PK) profile, and preliminary antitumor activity of single and multiple doses of PLB1001 in Patients with PTPRZ1-MET fusion gene positive recurrent high-grade Gliomas.

Description:

This is a Phase I, open-label study of PLB1001 administered orally to patients with PTPRZ1-MET fusion gene positive recurrent high-grade Gliomas. The aim of dose-escalation study is to estimate the MTD and to identify the dose-limiting toxicity(DLT) and the recommended phase II dose (RP2D) for PLB1001 single agent as well as to determine the PK/PD profile. Aprox. 20 patients will be enrolled in this study.

PLB1001 is a potent selective c-Met inhibitor. PLB1001 acts on cancer by blocking abnormal cMET-mediated signaling (including PTPRZ1-MET fusion gene), leading to profound tumor growth inhibition in xenografts of PTPRZ1-MET fusion gene positive glioblastoma tumor.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: December 2018
• Est. primary completion date: April 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Signed Informed Consent Form

• Age=18 years

• Histologically or cytologically confirmed recurrent high-grade glioma after concurrent or adjuvant chemoradiotherapy

• Prior treatment with temozolomide

• Must have evidence of PTPRZ1-MET fusion gene positivity from the results of molecular pre-screening evaluations

• At least one measurable lesion as per RANO

• No evidence of recent haemorrhage on baseline MRI of the brain

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

• Major surgery within 4 weeks prior to first dose of PLB1001

• Previous anti-cancer and investigational agents within 4 weeks before first dose of PLB1001. If previous treatment is a monoclonal antibody, then the treatment must be discontinued at least 6 weeks before first dose of PLB1001

• Pregnant or nursing women

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

• Prior therapy with gamma knife or other focal high-dose radiotherapy is allowed, but the patient must have subsequent histologic documentation of recurrence, unless the recurrence is a new lesion outside the irradiated field

• Karnofsky performance status = 50%

Exclusion Criteria:

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

• The subject is unable to undergo MRI scan (e.g. has pacemaker)

• Clinically significant, uncontrolled heart diseases: Unstable angina; History of documented congestive heart failure (New York Heart Association functional classification> II); Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) = 145 mm Hg and/or Diastolic Blood Pressure (DBP) =85 mm Hg; Arrhythmias.

• Active peptic ulcer disease or gastritis

• Adverse events from prior anti-cancer therapy that have not resolved to Grade = 1, except for alopecia

• Major surgery within 4 weeks prior to first dose of PLB1001

• Previous anti-cancer and investigational agents within 4 weeks before first dose of PLB1001. If previous treatment is a monoclonal antibody, then the treatment must be discontinued at least 6 weeks before first dose of PLB1001

• Pregnant or nursing women

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

Related Conditions & MeSH terms

• Glioma

Intervention

Drug:
• PLB1001
PLB1001 is a capsule in the form of 25 mg and 100mg, twice daily.

Locations

Country	Name	City	State
China	Beijing Shijitan Hospital,CMU	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	Percentage of participants with dose-limiting toxicities	The primary endpoint is evaluation of safety and tolerability during all the study of therapy following the initiation of single and multiple doses of PLB1001. The safety and tolerability variables to be evaluated in this study are adverse events, vital signs, and electrocardiograms (ECGs), Incidence and nature of DLTs (Dose-Limiting Toxicities), to determine the MTD (Maximum Tolerated Dose).	2 years
Secondary	Area under the plasma concentration versus time curve (AUC) of PLB1001 and its metabolite	In the study of single-dose, full Pharmacokinetics(PK) profiles of PLB1001 will be obtained following administration of a single oral dose of PLB1001 on Day 1 to Day 2. At multiple-dose, Pharmacokinetics(PK) sampling will include a pre-dose and at the 0.5, 1, 2, 4, 6, 8, 10, 12, 14 and 16 hour time points on days 1and 15 of dosing in the first 28-Day cycle of therapy, and pre-dose on days 2, 16 and 17 of the first 28-Day cycle of therapy	Day 1-3 Single Dose and Day 1-28 Steady State
Secondary	Maximum plasma concentration observed (Cmax) of PLB1001 and its metabolite	In the study of single-dose, full Pharmacokinetics(PK) profiles of PLB1001 will be obtained following administration of a single oral dose of PLB1001 on Day 1 to Day 2. At multiple-dose, Pharmacokinetics(PK) sampling will include a pre-dose and at the 0.5, 1, 2, 4, 6, 8, 10, 12, 14 and 16 hour time points on days 1and 15 of dosing in the first 28-Day cycle of therapy, and pre-dose on days 2, 16 and 17 of the first 28-Day cycle of therapy	Day 1-3 Single Dose and Day 1-28 Steady State
Secondary	Time to Cmax (Tmax) of PLB1001 and its metabolite	In the study of single-dose, full Pharmacokinetics(PK) profiles of PLB1001 will be obtained following administration of a single oral dose of PLB1001 on Day 1 to Day 2. At multiple-dose, Pharmacokinetics(PK) sampling will include a pre-dose and at the 0.5, 1, 2, 4, 6, 8, 10, 12, 14 and 16 hour time points on days 1and 15 of dosing in the first 28-Day cycle of therapy, and pre-dose on days 2, 16 and 17 of the first 28-Day cycle of therapy	Day 1-3 Single Dose and Day 1-28 Steady State
Secondary	Preliminary antitumor activity of PLB1001	Preliminary antitumor activity of PLB1001 assessed using RANO	2 years