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

• ClinicalTrials.gov Identifier: NCT04388475
• Recruitment Status: Active, not recruiting
• First Posted: May 14, 2020
• Last Update Posted: October 26, 2022
• Sponsor: Oblato, Inc.
• Information provided by (Responsible Party): Oblato, Inc.

Tracking Information

• First Submitted Date: May 6, 2020
• First Posted Date: May 14, 2020
• Last Update Posted Date: October 26, 2022
• Actual Study Start Date: June 12, 2020
• Estimated Primary Completion Date: July 31, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 11, 2020)

• Incidents of Adverse Events during the subjects are taking OKN-007 with Temozolomide [ Time Frame: Through study completion up to 24 months ]
  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 [ Time Frame: Change from baseline at Day 1 of each 28 day cycle ]
  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 [ Time Frame: Change from baseline at Day 1 of each 28 day cycle ]
  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 [ Time Frame: 6 months ]
  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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 11, 2020)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Recurrent Malignant Glioma
• Brain Glioblastoma

Intervention

• 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 Name: 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 Name: Temodar

Study Arms

Experimental: All patients

All patients enrolled in this study

Interventions:

• Drug: OKN-007
• Drug: Temozolomide (TMZ)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: October 25, 2022): 57
• Original Estimated Enrollment (submitted: May 11, 2020): 56
• Estimated Study Completion Date: March 31, 2024
• Estimated Primary Completion Date: July 31, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04388475
• Other Study ID Numbers: OKN-007-IV-RMG-201
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Oblato, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Oblato, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Oblato, Inc.
• Verification Date: August 2022