Clinical Trials /

Open-label Study Investigating of OKN-007 Combined With Temozolomide in Patients With Recurrent Glioblastoma

NCT04388475

Description:

This is a phase II open-label study investigating the efficacy, safety and pharmacokinetic(PK) properties of OKN-007 combined with temozolomide(TMZ) in patients with recurrent glioblastoma(GBM). All patients will have been previously treated with the standard-of-care treatment which includes surgical resection, radiation and chemotherapy, and in some cases treatment for recurrent disease. Patients with unequivocal recurrence (first or greater) established by MRI and meeting inclusion and exclusion criteria, will be eligible for OKN-007 treatment on this protocol.

Related Conditions:
  • Glioblastoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Open-label Study Investigating of OKN-007 Combined With Temozolomide in Patients With Recurrent Glioblastoma
  • Official Title: A Phase II Open-label Study Investigating the Efficacy, Safety and Pharmacokinetic Properties of OKN-007 Combined With Temozolomide in Patients With Recurrent Glioblastoma

Clinical Trial IDs

  • ORG STUDY ID: OKN-007-IV-RMG-201
  • NCT ID: NCT04388475

Conditions

  • Recurrent Malignant Glioma
  • Brain Glioblastoma

Interventions

DrugSynonymsArms
OKN-007All patients
Temozolomide (TMZ)All patients

Purpose

This is a phase II open-label study investigating the efficacy, safety and pharmacokinetic(PK) properties of OKN-007 combined with temozolomide(TMZ) in patients with recurrent glioblastoma(GBM). All patients will have been previously treated with the standard-of-care treatment which includes surgical resection, radiation and chemotherapy, and in some cases treatment for recurrent disease. Patients with unequivocal recurrence (first or greater) established by MRI and meeting inclusion and exclusion criteria, will be eligible for OKN-007 treatment on this protocol.

Trial Arms

NameTypeDescriptionInterventions
All patientsExperimentalAll patients enrolled in this study
  • OKN-007
  • Temozolomide (TMZ)

Eligibility Criteria

        Inclusion Criteria:

          1. Confirmed histopathology of recurrent GBM (WHO Grade IV), following primary treatment
             with TMZ and radiotherapy (minimum of 50 Gy) and at least two cycles of maintenance
             TMZ (5 days of a 28 day cycle).

          2. Patients must have tumor tissue samples available from the GBM surgery or open biopsy
             for O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status analysis
             or must have medical record available to document MGMT status.

          3. Unequivocal radiographic evidence of tumor progression by MRI

          4. At least one measurable lesion per RANO criteria within 21 days prior to registration.

          5. No more than one prior line of therapy for glioblastoma.

          6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

          7. Full recovery (≤ grade 1) from the toxic effects.

          8. Adequate renal, liver and bone marrow function:

               -  Hemoglobin >9.0 g/dL

               -  Leukocytes >3,000/mcL

               -  Absolute neutrophil count >1,500/mcL

               -  Platelets >100,000/mcL

               -  Total bilirubin ≤ 1.5 × upper limit of normal (ULN)

               -  AST (SGOT) / ALT (SGPT) ≤2.5 × ULN

               -  Creatinine clearance ≥ 60 mL/min

        10. Patients must be ≥18 years of age

        Exclusion Criteria:

          1. Early discontinuation of TMZ in first line due to treatment related Adverse events
             (AEs).

          2. Second primary malignancy expected to require treatment within a 6 month period
             (except adequately treated basal cell carcinoma of the skin).

          3. Have received treatment within the last 28 days with a drug that has not received
             regulatory approval for any indication at the time of study entry.

          4. Serious concomitant systemic disorders

          5. Patients with abnormal sodium, potassium, or creatinine levels ≥ grade 2.

          6. Patients with prothrombin time/partial thromboplastin time (PT/PTT) or International
             normalized ratio (INR) above the ULN.

          7. Inability to comply with protocol or study procedures.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidents of Adverse Events during the subjects are taking OKN-007 with Temozolomide
Time Frame:Through study completion up to 24 months
Safety Issue:
Description:Evaluate incidents of Adverse Events during the subjects are taking OKN-007 with Temozolomide. Adverse events will be graded according to Common Terminology Criteria for Adverse Events (CTCAE, version 5.0).

Secondary Outcome Measures

Measure:Radiographic response rate
Time Frame:24 months
Safety Issue:
Description:To determine the objective response rate to study therapy using Radiographic Assessment in Neuro-Oncology (RANO) criteria.
Measure:Progression Free Survival (PFS) rate
Time Frame:6 months
Safety Issue:
Description:Proportion of subjects who are alive and progression free after six months of starting treatment. PFS is defined as the time from first treatment dose until objective tumor progression on the RANO criteria or death.
Measure:Cmax of OKN-007 in blood plasma
Time Frame:Day 1 and Day 5 in Cycle 1 and 2 (28 Day Cycle)
Safety Issue:
Description:The sample will be collected at 10 time points during 24 hours after OKN-007 administration.
Measure:AUC of OKN-007 in blood plasma
Time Frame:Day 1 and Day 5 in Cycle 1 and 2 (28 Day Cycle)
Safety Issue:
Description:The sample will be collected at 10 time points during 24 hours after OKN-007 administration.
Measure:Tmax of OKN-007 in blood plasma
Time Frame:Day 1 and Day 5 in Cycle 1 and 2 (28 Day Cycle)
Safety Issue:
Description:The sample will be collected at 10 time points during 24 hours after OKN-007 administration.
Measure:Cmax of Temozolomide in blood plasma
Time Frame:Day 1 and Day 5 in Cycle 1 and 2 (28 Day Cycle)
Safety Issue:
Description:The sample will be collected at 8 time points during 24 hours after Temozolomide administration.
Measure:AUC of Temozolomide in blood plasma
Time Frame:Day 1 and Day 5 in Cycle 1 and 2 (28 Day Cycle)
Safety Issue:
Description:The sample will be collected at 8 time points during 24 hours after Temozolomide administration.
Measure:Tmax of Temozolomide in blood plasma
Time Frame:Day 1 and Day 5 in Cycle 1 and 2 (28 Day Cycle)
Safety Issue:
Description:The sample will be collected at 8 time points during 24 hours after Temozolomide administration.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Oblato, Inc.

Last Updated

June 29, 2020