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

Sponsor
Oblato, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04388475
Collaborator
(none)
56
Enrollment
13
Locations
1
Arm
45.6
Anticipated Duration (Months)
4.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
56 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jun 12, 2020
Anticipated Primary Completion Date :
Jul 31, 2023
Anticipated Study Completion Date :
Mar 31, 2024

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Incidents of Adverse Events during the subjects are taking OKN-007 with Temozolomide [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).

    2. Number of subjects with decreased neurological function [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).

    3. Number of subjects with decreased performance [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).

    4. Overall Survival (OS) rate [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.

    Secondary Outcome Measures

    1. Radiographic response rate [24 months]

      To determine the objective response rate to study therapy using Radiographic Assessment in Neuro-Oncology (RANO) criteria.

    2. Progression Free Survival (PFS) rate [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.

    3. Cmax of OKN-007 in blood plasma [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.

    4. AUC of OKN-007 in blood plasma [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.

    5. Tmax of OKN-007 in blood plasma [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.

    6. Cmax of Temozolomide in blood plasma [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.

    7. AUC of Temozolomide in blood plasma [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.

    8. Tmax of Temozolomide in blood plasma [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    1. 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).

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Birmingham Alabama United States 35294
    2 St. Joseph's Hospital and Medical Center Phoenix Arizona United States 85013
    3 Providence Saint John's Health Center - John Wayne Cancer Institute Santa Monica California United States 90404
    4 Swedish Medical Center Englewood Colorado United States 80113
    5 AdventHealth Orlando Orlando Florida United States 32804
    6 University of Iowa Iowa City Iowa United States 52242
    7 Norton Healthcare Louisville Kentucky United States 40241
    8 Henry Ford Health System Detroit Michigan United States 48202
    9 Wake Forest Baptist Comprehensive Cancer Center Winston-Salem North Carolina United States 27157
    10 The University of Toledo Toledo Ohio United States 43606
    11 The University of Oklahoma Oklahoma City Oklahoma United States 73117
    12 Lifespan Office of Research Providence Rhode Island United States 02903
    13 St. Joseph Hospital of Orange Seattle Washington United States 35143

    Sponsors and Collaborators

    • Oblato, Inc.

    Investigators

    • Study Director: Shinwook Kang, Oblato, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Oblato, Inc.
    ClinicalTrials.gov Identifier:
    NCT04388475
    Other Study ID Numbers:
    • OKN-007-IV-RMG-201
    First Posted:
    May 14, 2020
    Last Update Posted:
    Aug 19, 2022
    Last Verified:
    Aug 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Glioblastoma
    Glioma
    Recurrence
    Temozolomide

    Study Results

    No Results Posted as of Aug 19, 2022