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

Primary Purpose

Recurrent Malignant Glioma, Brain Glioblastoma

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
OKN-007
Temozolomide (TMZ)
Sponsored by
Oblato, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Malignant Glioma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Confirmed Glioblastoma based on histopathology or molecular profile analysis (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) as first-line or second-line treatment with another treatment regimen, excluding bevacizumab.
  2. Patients must have medical records available documenting O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status analysis or must have tumor tissue samples available from prior GBM surgery or open biopsy for MGMT status determination.
  3. For patients with unresected recurrent tumor, unequivocal radiographic evidence of tumor progression by MRI. These patients must have at least one measurable lesion.
  4. Patients with recent resection of recurrent viable tumor are eligible following post-operative MRI perfusion scan with or without measurable lesions.
  5. No more than two prior lines of therapy for glioblastoma. Any second-line therapy is acceptable, excluding bevacizumab as second line.
  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
  9. Patients must be ≥18 years of age

Exclusion Criteria:

  1. Early discontinuation of TMZ in prior 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. Have received chemotherapeutic agents (including temozolomide) within 28 days or within 5 half-lives for non-cytotoxic agents (whichever is shorter) of study entry
  5. Serious concomitant systemic disorders
  6. Patients with abnormal sodium, potassium, or creatinine levels ≥ grade 2.
  7. Patients with prothrombin time/partial thromboplastin time (PT/PTT) or International normalized ratio (INR) above the ULN.
  8. Inability to comply with protocol or study procedures.
  9. Patients who have received bevacizumab for recurrent glioblastoma or are planning to initiate treatment with bevacizumab for tumor necrosis. (Past treatment with bevacizumab for tumor necrosis is acceptable).
  10. Patients receiving or planning to initiate treatment with the tumor treating fields device (Optune®) (Optune® prior to enrollment is permitted).

Sites / Locations

  • University of Alabama at Birmingham
  • St. Joseph's Hospital and Medical Center
  • Providence Saint John's Health Center - John Wayne Cancer Institute
  • Swedish Medical Center
  • AdventHealth Orlando
  • University of Iowa
  • Norton Healthcare
  • Henry Ford Health System
  • Wake Forest Baptist Comprehensive Cancer Center
  • The University of Toledo
  • The University of Oklahoma
  • Lifespan Office of Research
  • St. Joseph Hospital of Orange

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

All patients

Arm Description

All patients enrolled in this study

Outcomes

Primary Outcome Measures

Incidents of Adverse Events during the subjects are taking OKN-007 with Temozolomide
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).
Number of subjects with decreased neurological function
Neurologic function assessed by Neurologic Assessment in Neuro-Oncology (NANO) scale. The NANO Scale evaluates 9 major domains of neurologic function, with each domain being scored on a range from 0 (no deficits) to 2 or 3 (maximum deficits).
Number of subjects with decreased performance
Number of participants with decreased performance assessed by Eastern Oncology Cooperative Group (ECOG) scale. Minimum 0 (normal function) and maximum 4 (maximum disability).
Overall Survival (OS) rate
Proportion of subjects who are alive after six months of starting treatment. OS is defined as the time from first treatment dose until date of death due to any cause.

Secondary Outcome Measures

Radiographic response rate
To determine the objective response rate to study therapy using Radiographic Assessment in Neuro-Oncology (RANO) criteria.
Progression Free Survival (PFS) rate
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.
Cmax of OKN-007 in blood plasma
The sample will be collected at 10 time points during 24 hours after OKN-007 administration.
AUC of OKN-007 in blood plasma
The sample will be collected at 10 time points during 24 hours after OKN-007 administration.
Tmax of OKN-007 in blood plasma
The sample will be collected at 10 time points during 24 hours after OKN-007 administration.
Cmax of Temozolomide in blood plasma
The sample will be collected at 8 time points during 24 hours after Temozolomide administration.
AUC of Temozolomide in blood plasma
The sample will be collected at 8 time points during 24 hours after Temozolomide administration.
Tmax of Temozolomide in blood plasma
The sample will be collected at 8 time points during 24 hours after Temozolomide administration.

Full Information

First Posted
May 6, 2020
Last Updated
October 25, 2022
Sponsor
Oblato, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04388475
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 12, 2020 (Actual)
Primary Completion Date
July 31, 2023 (Anticipated)
Study Completion Date
March 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Oblato, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Malignant Glioma, Brain Glioblastoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
57 (Actual)

8. Arms, Groups, and Interventions

Arm Title
All patients
Arm Type
Experimental
Arm Description
All patients enrolled in this study
Intervention Type
Drug
Intervention Name(s)
OKN-007
Other Intervention Name(s)
NXY-059, HPN-07
Intervention Description
Drug: OKN-007 (400 mg OKN-007/mL in a phosphate buffer) Administered via IV infusion, at a dose level of 60 mg/kg, given three times a week for 12 weeks, two times a week for a further 12 weeks and once per week until disease progression or up to two years.
Intervention Type
Drug
Intervention Name(s)
Temozolomide (TMZ)
Other Intervention Name(s)
Temodar
Intervention Description
Administered via oral, at a dose level of 150 mg/m2, once daily on Days 1-5 of each 28 day cycle in Cycle 1. If this dose level is tolerated, then in Cycle 2 (and subsequent cycles), at a dose level of 200 mg/m2, once daily on Days 1-5 of each 28 day cycle.
Primary Outcome Measure Information:
Title
Incidents of Adverse Events during the subjects are taking OKN-007 with Temozolomide
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).
Time Frame
Through study completion up to 24 months
Title
Number of subjects with decreased neurological function
Description
Neurologic function assessed by Neurologic Assessment in Neuro-Oncology (NANO) scale. The NANO Scale evaluates 9 major domains of neurologic function, with each domain being scored on a range from 0 (no deficits) to 2 or 3 (maximum deficits).
Time Frame
Change from baseline at Day 1 of each 28 day cycle
Title
Number of subjects with decreased performance
Description
Number of participants with decreased performance assessed by Eastern Oncology Cooperative Group (ECOG) scale. Minimum 0 (normal function) and maximum 4 (maximum disability).
Time Frame
Change from baseline at Day 1 of each 28 day cycle
Title
Overall Survival (OS) rate
Description
Proportion of subjects who are alive after six months of starting treatment. OS is defined as the time from first treatment dose until date of death due to any cause.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Radiographic response rate
Description
To determine the objective response rate to study therapy using Radiographic Assessment in Neuro-Oncology (RANO) criteria.
Time Frame
24 months
Title
Progression Free Survival (PFS) rate
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.
Time Frame
6 months
Title
Cmax of OKN-007 in blood plasma
Description
The sample will be collected at 10 time points during 24 hours after OKN-007 administration.
Time Frame
Day 1 and Day 5 in Cycle 1 and 2 (28 Day Cycle)
Title
AUC of OKN-007 in blood plasma
Description
The sample will be collected at 10 time points during 24 hours after OKN-007 administration.
Time Frame
Day 1 and Day 5 in Cycle 1 and 2 (28 Day Cycle)
Title
Tmax of OKN-007 in blood plasma
Description
The sample will be collected at 10 time points during 24 hours after OKN-007 administration.
Time Frame
Day 1 and Day 5 in Cycle 1 and 2 (28 Day Cycle)
Title
Cmax of Temozolomide in blood plasma
Description
The sample will be collected at 8 time points during 24 hours after Temozolomide administration.
Time Frame
Day 1 and Day 5 in Cycle 1 and 2 (28 Day Cycle)
Title
AUC of Temozolomide in blood plasma
Description
The sample will be collected at 8 time points during 24 hours after Temozolomide administration.
Time Frame
Day 1 and Day 5 in Cycle 1 and 2 (28 Day Cycle)
Title
Tmax of Temozolomide in blood plasma
Description
The sample will be collected at 8 time points during 24 hours after Temozolomide administration.
Time Frame
Day 1 and Day 5 in Cycle 1 and 2 (28 Day Cycle)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Confirmed Glioblastoma based on histopathology or molecular profile analysis (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) as first-line or second-line treatment with another treatment regimen, excluding bevacizumab. Patients must have medical records available documenting O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status analysis or must have tumor tissue samples available from prior GBM surgery or open biopsy for MGMT status determination. For patients with unresected recurrent tumor, unequivocal radiographic evidence of tumor progression by MRI. These patients must have at least one measurable lesion. Patients with recent resection of recurrent viable tumor are eligible following post-operative MRI perfusion scan with or without measurable lesions. No more than two prior lines of therapy for glioblastoma. Any second-line therapy is acceptable, excluding bevacizumab as second line. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 Full recovery (≤ grade 1) from the toxic effects. 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 Patients must be ≥18 years of age Exclusion Criteria: Early discontinuation of TMZ in prior line due to treatment related Adverse events (AEs). Second primary malignancy expected to require treatment within a 6 month period (except adequately treated basal cell carcinoma of the skin). 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. Have received chemotherapeutic agents (including temozolomide) within 28 days or within 5 half-lives for non-cytotoxic agents (whichever is shorter) of study entry Serious concomitant systemic disorders Patients with abnormal sodium, potassium, or creatinine levels ≥ grade 2. Patients with prothrombin time/partial thromboplastin time (PT/PTT) or International normalized ratio (INR) above the ULN. Inability to comply with protocol or study procedures. Patients who have received bevacizumab for recurrent glioblastoma or are planning to initiate treatment with bevacizumab for tumor necrosis. (Past treatment with bevacizumab for tumor necrosis is acceptable). Patients receiving or planning to initiate treatment with the tumor treating fields device (Optune®) (Optune® prior to enrollment is permitted).
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
St. Joseph's Hospital and Medical Center
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
Facility Name
Providence Saint John's Health Center - John Wayne Cancer Institute
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Swedish Medical Center
City
Englewood
State/Province
Colorado
ZIP/Postal Code
80113
Country
United States
Facility Name
AdventHealth Orlando
City
Orlando
State/Province
Florida
ZIP/Postal Code
32804
Country
United States
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Norton Healthcare
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40241
Country
United States
Facility Name
Henry Ford Health System
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Wake Forest Baptist Comprehensive Cancer Center
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
The University of Toledo
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43606
Country
United States
Facility Name
The University of Oklahoma
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73117
Country
United States
Facility Name
Lifespan Office of Research
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Facility Name
St. Joseph Hospital of Orange
City
Seattle
State/Province
Washington
ZIP/Postal Code
35143
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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