OKN-007 in Combination With Adjuvant Temozolomide Chemoradiotherapy for Newly Diagnosed Glioblastoma

Feasibility Pilot Study of OKN-007 in Combination With Adjuvant Temozolomide Chemoradiotherapy in Patients With Newly Diagnosed Glioblastoma

This is a pilot study exploring the potential benefit of adding OKN-007 with Temozolomide for treatment in patients with malignant Glioblastoma undergoing adjuvant concomitant radiotherapy. This drug combination is expected to have an anti-cancer effect in patients who have experienced disease progression after first line treatment.

Study Overview

• Status: Active, not recruiting
• Conditions: Glioblastoma
• Intervention / Treatment: Drug: OKN 007; Drug: Temozolomide; Radiation: Photon/Proton IMRT

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: James Battiste, MD; Phone Number: 405 271-8001; Email: james-battiste@ouhsc.edu
• Study Contact Backup: Name: Ingrid Block, MD; Phone Number: 405 271-8001; Email: ingrid-block@ouhsc.edu

Study Locations

• United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73117
      • Stephenson Cancer Center, University of Oklahoma Health Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients have newly diagnosed histologically proven WHO grade III or grade IV Glioblastoma Multiforme (GBM).
• Patients at initial presentation of GBM must undergo an adequate surgical resection of the primary lesion; patients must be registered within 49 days (7 weeks) of the surgery.
• Patients must have available and be willing to submit a minimum of five unstained slides tumor tissue specimens from the GBM surgery or open biopsy for MGMT status analysis and molecular profile analysis.
• ECOG performance status within 0 - 2
• Full recovery (< grade 1) from the adverse events associated with prior surgery or any earlier intervention and a minimum of 28 days from the administration of any investigational agent
• Adequate renal, liver and bone marrow function: Leukocytes >3,000/mcL; Absolute neutrophil count >1,500/mcL; Platelets >100,000/mcL; AST / ALT (SGPT) <2.5 x ULN; Total bilirubin ≤ 1.5 x institutional upper limit of normal (IULN) (except Gilbert's Syndrome, who must have a total bilirubin < 3.0 mg/dL); Creatinine within normal limits
• Patients must be ≥ 18 years of age
• Patients must be willing to have blood draws for PK analysis
• All patients must have a CT or MRI of the brain within 14 days prior to registration. The brain CT or MRI should be performed with intravenous contrast (unless contraindicated).
• Patients must be informed of the investigational nature of this study and must sign and give written informed consent for this protocol in accordance with institutional and federal guidelines.
• Life expectancy ≥ 3 months, allowing adequate follow up of toxicity evaluation and progression-free survival evaluation;
• Female patient, if of childbearing potential, has a negative serum pregnancy test within 72 hours of taking study medication and agrees to abstain from activities that could result in pregnancy from enrollment through 120 days after the last dose of study treatment
• Male patient agrees to use an adequate method of contraception
• Birth control should be used from the signing of the patient consent form and for 120 days following the last dose of study treatment.
• In addition, men must not donate sperm during study therapy and for 120 days after receiving the last dose of study treatment.

Exclusion Criteria:

• Second primary malignancy (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
• 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
• Serious concomitant systemic disorders (for example, active infection or abnormal electrocardiogram (ECG) indicative of cardiac disease) that, in the opinion of the investigator, would compromise the safety of the patient and his/her ability to complete the study
• Patients with moderate or severe renal impairment (calculated creatinine clearance of < 60 mL/min)
• Patients with sodium, potassium, or creatinine serum electrolytes > grade 2.
• Screening ECG abnormality documented by the investigator as medically significant
• Inability to comply with protocol or study procedures.
• Women who are pregnant or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OKN-007 3 days per week plus temozolomide; OKN-007: 60 mg/kg, IV, 3 times a week Temozolomide: 75 mg/m2, oral, once daily for 42 days Radiotherapy: 60 Gy administered in 30 fractions	Drug: OKN 007; 400 mg OKN-007/mL in a phosphate buffer; Drug: Temozolomide; 75 mg/m2; Radiation: Photon/Proton IMRT; standard of care treatment to be given 1 to 2 hours after OKN-007
Experimental: OKN-007 5 days per week and temozolomide; OKN-007: 60 mg/kg, IV, 5 times a week Temozolomide: 75 mg/m2, oral, once daily for 42 days Radiotherapy: 60 Gy administered in 30 fractions	Drug: OKN 007; 400 mg OKN-007/mL in a phosphate buffer; Drug: Temozolomide; 75 mg/m2; Radiation: Photon/Proton IMRT; standard of care treatment to be given 1 to 2 hours after OKN-007

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The maximum tolerated dose and the type of dose limiting toxicities	To determine how well patients are able to tolerate combination of OKN-007, temozolomide, and radiotherapy. Adverse events will be tabulated using MedDRA. The severity of the AE will be graded by the Investigator using the NCI CTCAE, version 4.03.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants who experience progression-free survival	To evaluate the proportion of patients who receive combination OKN-007 and TMZ who do not experience progression	5 years
Number of participants who comply with study treatment plan	To evaluate the clinical compliance of participants receiving combination OKN-007 and TMZ	5 years
Number of participants who are able to receive a reduction in steroid dose	To evaluate whether study drug combination allows for a reduced steroid dosage	5 years
Number of participants who experience overall survival	To evaluate the proportion of patients who receive combination OKN-007 and TMZ who experience overall survival	5 years

Collaborators and Investigators

• Sponsor: University of Oklahoma
• Investigators: Principal Investigator: James Battiste, MD, Principal Investigator

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2018
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): November 1, 2025

Study Registration Dates

• First Submitted: June 4, 2018
• First Submitted That Met QC Criteria: July 12, 2018
• First Posted (Actual): July 16, 2018

Study Record Updates

• Last Update Posted (Estimated): February 15, 2024
• Last Update Submitted That Met QC Criteria: February 13, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: OU-SCC-Oblato-001; OKN-007 (Other Grant/Funding Number: Oblato Inc)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No