OKN-007 and Temozolomide in Treating Patients with Grade III-IV Glioblastoma Multiforme Undergoing Adjuvant Concomitant Radiotherapy
This early phase I trial studies the side effects of OKN-007 and temozolomide in treating patients with grade III-IV glioblastoma multiforme undergoing concomitant radiotherapy after surgery. OKN-007 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving OKN-007 and temozolomide chemo-radiotherapy may work better in treating patients with glioblastoma multiforme after surgery.
Inclusion Criteria
- Patients have newly diagnosed histologically proven World Health Organization (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
- Eastern Cooperative Oncology Group (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
- Leukocytes > 3,000/mcL
- Absolute neutrophil count > 1,500/mcL
- Platelets > 100,000/mcL
- Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x upper limit of normal (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)
- Patients must be willing to have blood draws for pharmacokinetics (PK) analysis
- All patients must have a computed tomography (CT) or magnetic resonance imaging (MRI) of the brain within 21 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 7 days 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. Acceptable methods of birth control include: * Two highly effective forms of contraception, defined as contraceptive methods with a failure rate of less than 1% per year when used consistently and correctly. Patients and their sexual partners who’ve undergone vasectomy or tubal occlusion must also use a male condom with spermicide. * Permanent sterilization, defined as hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or bilateral orchidectomy * Postmenopausal, defined as a female patient or sexual partner > 45 years of age who has not menstruated for at least 12 consecutive months * Total sexual abstinence
- 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
Additional locations may be listed on ClinicalTrials.gov for NCT03587038.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVE:
I. To evaluate the safety and tolerability of PBN derivative OKN-007 (OKN-007) and temozolomide (TMZ) combination in patients with malignant glioblastoma undergoing adjuvant concomitant radiotherapy.
SECONDARY OBJECTIVES:
I. To evaluate progression free survival (PFS) and overall survival time (OS) for patients treated with adjuvant concomitant chemo-radiotherapy utilizing OKN-007 and TMZ combination.
II. To observe the clinical compliance of OKN-007 and TMZ combination regimen in patients with malignant glioblastoma undergoing adjuvant concomitant radiotherapy.
III. To evaluate if OKN-007 and TMZ combination can reduce steroid dose.
EXPLORATORY OBJECTIVES:
I. To investigate the molecular profile associated with the anti-cancer effect of chemoradiotherapy plus OKN-007 if data from FoundationOne is available as part of standard of care.
II. To compare the genetic analysis at pre- and post-treatment of chemo-radiotherapy plus OKN-007.
III. To evaluate drug exposure of OKN-007 in combination with TMZ.
OUTLINE:
CONCOMITANT PHASE: Patients receive OKN-007 intravenously (IV) thrice or 5 times weekly for up to 42 days in the absence of disease progression or unacceptable toxicity. Patients also receive TMZ orally (PO) once daily (QD) on days 1- 42 and undergo photon or proton intensity-modulated radiation therapy (IMRT) over 30 fractions in the absence of disease progression or unacceptable toxicity.
PRE-MAINTENANCE PHASE: Patients receive OKN-007 IV thrice weekly for up to 28 days in the absence of disease progression or unacceptable toxicity.
MAINTENANCE PHASE: Beginning 4 weeks after concomitant phase completion, patients receive OKN-007 IV thrice weekly of cycles 1-6, twice weekly of cycles 7-9, and once weekly of subsequent cycles. Patients also receive TMZ PO QD on days 1-5 of cycles 1-6. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo magnetic resonance imaging (MRI), computed tomography (CT) scan, and blood sample collection throughout the study.
After completion of study treatment, patients are followed up every 2 months for 1 year, and then annually for 3 years.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationUniversity of Oklahoma Health Sciences Center
Principal InvestigatorJames Douglas Battiste
- Primary IDOU-SCC-OBLATO-001
- Secondary IDsNCI-2018-03791
- ClinicalTrials.gov IDNCT03587038