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

Recurrent Malignant Glioma Clinical Trial

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04388475
• Other study ID #: OKN-007-IV-RMG-201
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 12, 2020
• Est. completion date: January 31, 2025

Study information

• Verified date: April 2024
• Source: Oblato, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 57
• Est. completion date: January 31, 2025
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Brain Glioblastoma
• Glioblastoma
• Glioma
• Recurrence
• Recurrent Malignant Glioma

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.
• 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.

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Henry Ford Health System	Detroit	Michigan
United States	Swedish Medical Center	Englewood	Colorado
United States	University of Iowa	Iowa City	Iowa
United States	Norton Healthcare	Louisville	Kentucky
United States	The University of Oklahoma	Oklahoma City	Oklahoma
United States	AdventHealth Orlando	Orlando	Florida
United States	St. Joseph's Hospital and Medical Center	Phoenix	Arizona
United States	Lifespan Office of Research	Providence	Rhode Island
United States	Providence Saint John's Health Center - John Wayne Cancer Institute	Santa Monica	California
United States	St. Joseph Hospital of Orange	Seattle	Washington
United States	The University of Toledo	Toledo	Ohio
United States	Wake Forest Baptist Comprehensive Cancer Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Oblato, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	Radiographic response rate	To determine the objective response rate to study therapy using Radiographic Assessment in Neuro-Oncology (RANO) criteria.	24 months
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)