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

NCT02978261 | Completed Phase 1

• 1 other identifier: HMO-PLB1001-I-GBM-01
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Glioma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Area under the plasma concentration versus time curve (AUC) of PLB1001 and its metabolite

  Day 1-3 Single Dose and Day 1-28 Steady State

• Maximum plasma concentration observed (Cmax) of PLB1001 and its metabolite

  Day 1-3 Single Dose and Day 1-28 Steady State

• Time to Cmax (Tmax) of PLB1001 and its metabolite

  Day 1-3 Single Dose and Day 1-28 Steady State

• Preliminary antitumor activity of PLB1001

  2 years

Study Arms (1)

PLB1001

EXPERIMENTAL

There are 4 dose cohorts, including 50mg BID,100mg BID, 200mg BID and 300mg BID in the dose escalation stage and PLB1001 will be administered orally to patients twice daily for each dose cohort.

Drug: PLB1001

Interventions

PLB1001 DRUG

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

Also known as: Bozitinib

PLB1001

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• Beijing Pearl Biotechnology Limited Liability Company: lead

Study Sites (1)

Beijing Shijitan Hospital,CMU

Beijing, Beijing Municipality, 100038, China

Location

Related Publications (1)

• Hu H, Mu Q, Bao Z, Chen Y, Liu Y, Chen J, Wang K, Wang Z, Nam Y, Jiang B, Sa JK, Cho HJ, Her NG, Zhang C, Zhao Z, Zhang Y, Zeng F, Wu F, Kang X, Liu Y, Qian Z, Wang Z, Huang R, Wang Q, Zhang W, Qiu X, Li W, Nam DH, Fan X, Wang J, Jiang T. Mutational Landscape of Secondary Glioblastoma Guides MET-Targeted Trial in Brain Tumor. Cell. 2018 Nov 29;175(6):1665-1678.e18. doi: 10.1016/j.cell.2018.09.038. Epub 2018 Oct 18.

  PMID: 30343896 DERIVED

MeSH Terms

Conditions

Glioma

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Wenbin Li, MD

  Beijing Shijitan Hospital, CMU

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2016
• First Posted: November 30, 2016
• Study Start: September 1, 2016
• Primary Completion: April 1, 2018
• Study Completion: December 1, 2018
• Last Updated: March 4, 2020

Record last verified: 2018-08

Locations

CN (1)