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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Recurrent Malignant Glioma; Brain Glioblastoma
• Intervention / Treatment: Drug: OKN-007; Drug: Temozolomide (TMZ)

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital and Medical Center
  • California
    • Santa Monica, California, United States, 90404
      • Providence Saint John's Health Center - John Wayne Cancer Institute
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Swedish Medical Center
  • Florida
    • Orlando, Florida, United States, 32804
      • AdventHealth Orlando
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kentucky
    • Louisville, Kentucky, United States, 40241
      • Norton Healthcare
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Comprehensive Cancer Center
  • Ohio
    • Toledo, Ohio, United States, 43606
      • The University of Toledo
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73117
      • The University of Oklahoma
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Lifespan Office of Research
  • Washington
    • Seattle, Washington, United States, 35143
      • St. Joseph Hospital of Orange

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: All patients; All patients enrolled in this study

Drug: OKN-007; 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.; Other Names: NXY-059, HPN-07; Drug: Temozolomide (TMZ); 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.; Other Names: Temodar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Through study completion up to 24 months
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).	Change from baseline at Day 1 of each 28 day cycle
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).	Change from baseline at Day 1 of each 28 day cycle
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.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic response rate	To determine the objective response rate to study therapy using Radiographic Assessment in Neuro-Oncology (RANO) criteria.	24 months
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.	6 months
Cmax of OKN-007 in blood plasma	The sample will be collected at 10 time points during 24 hours after OKN-007 administration.	Day 1 and Day 5 in Cycle 1 and 2 (28 Day Cycle)
AUC of OKN-007 in blood plasma	The sample will be collected at 10 time points during 24 hours after OKN-007 administration.	Day 1 and Day 5 in Cycle 1 and 2 (28 Day Cycle)
Tmax of OKN-007 in blood plasma	The sample will be collected at 10 time points during 24 hours after OKN-007 administration.	Day 1 and Day 5 in Cycle 1 and 2 (28 Day Cycle)
Cmax of Temozolomide in blood plasma	The sample will be collected at 8 time points during 24 hours after Temozolomide administration.	Day 1 and Day 5 in Cycle 1 and 2 (28 Day Cycle)
AUC of Temozolomide in blood plasma	The sample will be collected at 8 time points during 24 hours after Temozolomide administration.	Day 1 and Day 5 in Cycle 1 and 2 (28 Day Cycle)
Tmax of Temozolomide in blood plasma	The sample will be collected at 8 time points during 24 hours after Temozolomide administration.	Day 1 and Day 5 in Cycle 1 and 2 (28 Day Cycle)

Collaborators and Investigators

• Sponsor: Oblato, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2020
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): January 31, 2025

Study Registration Dates

• First Submitted: May 6, 2020
• First Submitted That Met QC Criteria: May 11, 2020
• First Posted (Actual): May 14, 2020

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Recurrence; Glioma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: OKN-007-IV-RMG-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No