Study of Safety and Pharmacokinetic Properties of Oral OKN-007 in Patients with Recurrent High-Grade Glioma

NCT ID: NCT05561374

Last Updated: 2024-11-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-04-17

Study Completion Date

2025-06-30

Brief Summary

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This is a phase 1 open-label, multicenter study to investigate tolerability, safety and PK properties of oral OKN-007 in patients with recurrent high-grade glioma.

Detailed Description

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This phase 1 open-label study is based on the traditional 3+3 design following the initial single-participant cohort to determine the maximum tolerated dose (MTD). Eligible participants will be enrolled each of the cohorts with escalated dose levels and administered the study drug OKN-007 orally daily in 28-day cycles: Cohort 1, Cohort 2, Cohort 3, Cohort 4. Participants may receive study treatment up to 2 years or until tumor progression, unacceptable toxicity, death, or patient withdrawal. The safety and pharmacokinetic properties of oral OKN-007 will be investigated.

Conditions

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High-grade Glioma Oligodendroglioma Astrocytoma Glioblastoma Multiforme

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Low-dose OKN-007, two times a day (BID)

Dose Escalation Cohort 1

Group Type EXPERIMENTAL

Low-dose OKN-007, BID

Intervention Type DRUG

Participants will be administered low doses of oral OKN-007 two times a day daily in 28-day cycles.

Low-dose OKN-007, three times a day (TID)

Dose Escalation Cohort 2

Group Type EXPERIMENTAL

Low-dose OKN-007, TID

Intervention Type DRUG

Participants will be administered low doses of oral OKN-007 three times a day daily in 28-day cycles.

Mid-dose OKN-007, three times a day (TID)

Dose Escalation Cohort 3

Group Type EXPERIMENTAL

Mid-dose OKN-007, TID

Intervention Type DRUG

Participants will be administered mid doses of oral OKN-007 three times a day daily in 28-day cycles.

High-dose OKN-007, three times a day (TID)

Dose Escalation Cohort 4

Group Type EXPERIMENTAL

High-dose OKN-007, TID

Intervention Type DRUG

Participants will be administered high doses of oral OKN-007 three times a day daily in 28-day cycles.

Interventions

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Low-dose OKN-007, BID

Participants will be administered low doses of oral OKN-007 two times a day daily in 28-day cycles.

Intervention Type DRUG

Low-dose OKN-007, TID

Participants will be administered low doses of oral OKN-007 three times a day daily in 28-day cycles.

Intervention Type DRUG

Mid-dose OKN-007, TID

Participants will be administered mid doses of oral OKN-007 three times a day daily in 28-day cycles.

Intervention Type DRUG

High-dose OKN-007, TID

Participants will be administered high doses of oral OKN-007 three times a day daily in 28-day cycles.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Confirmed recurrent gliomas that were originally diagnosed as high-grade glioma (World Health Organization \[WHO\] Grade 3 or 4; astrocytoma, oligodendroglioma, or glioblastoma) by histopathology or molecular studies.
2. Progressive or recurrent gliomas documented by magnetic resonance imaging (MRI) no earlier than 180 days after first surgery for gliomas and no earlier than 90 days after completion of radiotherapy (applies to patients with first progression/recurrence only).
3. Patients must have medical records available documenting known histology or molecular and genetic information resulting from prior analyses, or tumor tissue samples available from prior glioma surgery or open biopsy for correlative research.
4. For patients with unresected recurrent tumor, unequivocal radiographic evidence of tumor progression by MRI as per the RANO criteria within 28 days prior to the first dose. These patients must have at least one measurable lesion per RANO.
5. No more than two prior lines of therapy for high-grade glioma (WHO Grade 3 or 4). The first-line therapy must include radiotherapy (minimum of 50 Gy; 34 Gy in elderly patients) with concomitant or adjuvant standard chemotherapy (temozolomide (TMZ), or procarbazine, lomustine and vincristine in patients with anaplastic oligodendroglioma).
6. Eastern Cooperative Oncology Group (ECOG) performance status \<2.
7. Full recovery (grade ≤1) from the toxic effects of any earlier intervention and a minimum of 28 days from the last administration of any investigational agent that has not received regulatory approval for any indication at the time of registration.
8. Adequate renal, liver and bone marrow function without packed red blood cell/platelet transfusions within 4 weeks of the date of lab test during screening:

* Leukocytes ≥3.0 × 10\^9/L
* Absolute neutrophil count (ANC) ≥1.5 × 10\^9/L
* Platelets ≥100 × 10\^9/L
* Hemoglobin ≥ 9.0 g/dL
* Total bilirubin ≤1.5 × upper limit of normal (ULN), unless documented Gilbert's syndrome.
* Aspartate transaminase/alanine transaminase ≤2.5 × ULN
* Creatinine clearance ≥60 mL/min calculated as per Cockcroft-Gault equation.
9. Patients must be ≥18 years of age.
10. Life expectancy (as assessed by the Investigator) at least three months.
11. Patients must not have significantly diseased or obstructed gastrointestinal tract, malabsorption, uncontrolled vomiting or diarrhea, or inability to swallow oral medications.
12. Have provided written informed consent.
13. Patients must be willing to have multiple blood draws for PK analysis.
14. Female patients, of childbearing potential, must have a negative serum pregnancy test within 7 days prior to study treatment initiation and agree to use adequate contraception or practice sexual abstinence as the preferred and usual lifestyle of the patient during the study and for up to 120 days (4 months) after the last dose of study treatment.
15. Male patients with female partners of childbearing potential must, even if surgically sterilized, agree to practice effective barrier contraception and practice true abstinence.
16. Human immunodeficiency virus infected patients on effective antiretroviral therapy with undetectable viral load within 6 months prior to study registration are eligible for this trial.

Exclusion Criteria

1. Prior malignancy (other than glioma) expected to require treatment within a 6-month period (except adequately treated basal cell carcinoma of the skin). Patients who had another malignancy in the past but have been free of active disease for more than 2 years, are eligible.
2. 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 registration.
3. Have received chemotherapeutic agents (including TMZ) within 28 days or within 5 half-lives for non-cytotoxic agents (whichever is shorter) of study registration.
4. Serious concomitant systemic disorders, for example, abnormal electrocardiogram (ECG) indicative of cardiac disease (patients with Fridericia-corrected QT interval \[QTcF\] \>480 msec.
5. Patients with abnormal sodium, potassium, or creatinine levels grade ≥2.
6. Inability to comply with protocol or study procedures.
7. Women who are pregnant or breastfeeding.
8. Patients who have received bevacizumab for recurrent glioblastoma or are planning to initiate treatment with bevacizumab for tumor necrosis.
9. Patients completing radiotherapy treatment less than 2 weeks prior to planned study treatment initiation.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Oblato, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Providence Saint John's Cancer Institute

Santa Monica, California, United States

Site Status

Norton Healthcare

Louisville, Kentucky, United States

Site Status

Atrium Health Wake Forest Baptist Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Site Status

The University of Oklahoma Health Sciences Center, Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Site Status

Countries

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United States

Other Identifiers

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OKN-007-OL-RMG-101

Identifier Type: -

Identifier Source: org_study_id