Clinical trial NCT04388475: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Recurrent Malignant Glioma
Brain Glioblastoma
Lead sponsor: Oblato, Inc.
Sponsor class: INDUSTRY
First posted: 2020-05-14
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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).

Primary outcomes:
measure: Incidents of Adverse Events during the subjects are taking OKN-007 with Temozolomide
timeFrame: Through study completion up to 24 months
measure: Overall Survival (OS) rate
timeFrame: 6 months
Secondary outcomes:
measure: Overall Response Rate (ORR%)
timeFrame: 24 months
measure: Progression Free Survival (PFS) rate
timeFrame: 6 months
measure: Cmax of OKN-007 in blood plasma
timeFrame: Day 1 and Day 5 in Cycle 1 and 2 (28 Day Cycle)
measure: AUC of OKN-007 in blood plasma
timeFrame: Day 1 and Day 5 in Cycle 1 and 2 (28 Day Cycle)
measure: Tmax of OKN-007 in blood plasma
timeFrame: Day 1 and Day 5 in Cycle 1 and 2 (28 Day Cycle)
measure: Cmax of Temozolomide in blood plasma
timeFrame: Day 1 and Day 5 in Cycle 1 and 2 (28 Day Cycle)
measure: AUC of Temozolomide in blood plasma
timeFrame: Day 1 and Day 5 in Cycle 1 and 2 (28 Day Cycle)
measure: Tmax of Temozolomide in blood plasma
timeFrame: Day 1 and Day 5 in Cycle 1 and 2 (28 Day Cycle)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: St. Joseph's Hospital and Medical Center
state: Arizona
city: Santa Monica
country: United States
facility: Providence Saint John's Health Center - John Wayne Cancer Institute
state: California
city: Englewood
country: United States
facility: Swedish Medical Center
state: Colorado
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Louisville
country: United States
facility: Norton Healthcare
state: Kentucky
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Comprehensive Cancer Center
state: North Carolina
city: Toledo
country: United States
facility: The University of Toledo
state: Ohio
city: Oklahoma City
country: United States
facility: The University of Oklahoma
state: Oklahoma
city: Providence
country: United States
facility: Lifespan Office of Research
state: Rhode Island
city: Seattle
country: United States
facility: St. Joseph Hospital of Orange
state: Washington
Study officials:
References: