None listed
Conditions
Brief summary
The purpose of this study is to assess whether the drug PAX-1 can delay cancer progression in patients with recurrence glioblastoma. Who is it for? You may be eligible for this study if you are aged 18 to 70, diagnosed with recurrent glioblastoma. Study details Participants who are resistant to SOC therapy will receive PAX-1 monotherapy alone until disease progression/recurrence or patient withdrawal (due to intolerance or withdrawal of consent).Patients will receive a maximum daily daily 15 mg oral dose of PAX-1 Every 8 weeks the patient will have a scan of their tumour to determine whether the therapy is working. It is hoped that information gained in this study will aid in the understanding of treatment of glioblastoma and help in the development of new approaches to its treatment and the care of future patients who share your condition.
Interventions
The changes to the trial were made after patient enrolment. At the time of protocol update, 6 patients were enrolled in the trial.
Initial HREC approval date, 16 August 2019. HREC approval date with update protocol tittle 22 April 2021.
Patients will receive PAX-1 monotherapy for maximum of 4 cycles (provision for additional cycles based on additional cycle criteria), until intolerance, non compliance, withdrawal of consent.
1. The first cycle will start at a dose of 10 mg/day PAX-1.
2. At the
The changes to the trial were made after patient enrolment. At the time of protocol update, 6 patients were enrolled in the trial. Initial HREC approval date, 16 August 2019. HREC approval date with update protocol tittle 22 April 2021. Patients will receive PAX-1 monotherapy for maximum of 4 cycles (provision for additional cycles based on additional cycle criteria), until intolerance, non compliance, withdrawal of consent. 1. The first cycle will start at a dose of 10 mg/day PAX-1. 2. At the end of the first cycle and for each treatment cycle thereafter, the PI will determine the dose of PAX-1 in the next treatment cycle, taking into account the patient's tolerance of the current dose of PAX-1. 3. If Cycle 1 is well tolerated by the patient, then Cycle 2 of PAX-1 will be at a dose of 12.5 mg/day PAX-1. 4. If Cycle 2 is well tolerated by the patient, then Cycle 3 of PAX-1 will be at a dose of 15 mg/day PAX-1. 5. If 15 mg/day PAX-1 is well tolerated by patients, then this dose will be continued for the rest of the cycles The patients will have an MRI every 8 weeks for disease assessment.
Sponsors
Novotech (Australia) Pty Limited
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Inclusion Criteria: 1. Patients with recurrent GBM (based on radiological or histological evidence of recurrence) who are resistant to SOC (radiation, second-line treatments including re surgery, or any other treatment deemed appropriate by the PI) 2. Male or female patients >18 years of age (or age of legal adult, whichever is older) and <70 years of age 3. Patients with an ECOG status 0-2 4. RANO criteria defined measurable disease as bidimensional contrast-enhancing lesions with clearly defined margins, with 2 perpendicular diameters of at least 10 mm by MRI imaging at baseline 5. Patients must have adequate haematological, hepatic and renal functions: • Absolute neutrophil count (ANC) = 1.5 x109/L • Platelet count = 100 x109/L • Haemoglobin = 90 g/L (> 9.0 g/dL) • Total bilirubin = 1.5 upper limit of normal (ULN) (< 2.5 ULN if patient has Gilbert’s syndrome) • AST/ALT = 2.5 x ULN; = 5 x ULN for patients with liver metastases • Serum creatinine within normal range or calculated creatinine clearance > 50 mL/min • Albumin = 33 g/L • International normalised ratio (INR) and activated partial thromboplastin time (APTT) < 1.5 ULN • Serum magnesium 0.70 to 1.10 mmol/L (magnesium replacement strategies may be used in case of deficiency) • Serum potassium = 3.5 mmol/L (potassium replacement strategies may be used in case of deficiency) • Serum electrolyte levels (e.g. calcium, phosphorus) within normal range or deemed not clinically significant by the Investigator. 6. The patient is able to take oral medication 7. Recovery from the effects of prior therapy, including minimum washout before enrolment in the study is as below: • 4 weeks from non-nitrosoureas cytotoxic agents (3 weeks from procarbazine, 2 weeks from vincristine) • 2 weeks from daily or metronomic chemotherapy (the patient must have recovered from the expected toxic effects of such therapy to their baseline or to grade 1) • 6 weeks from nitrosoureas cytotoxic agents • 4 weeks from any investigational agents • 1 week from non-cytotoxic agents 12 weeks from radiotherapy to minimize the potential for MRI changes related to radiation necrosis that might be misdiagnosed as progression of disease, or 4 weeks if a new lesion, relative to the pre-radiation MRI, develops that is outside the primary radiation field 8. Women of childbearing potential (WOCBP) must have a negative serum beta- human chorionic gonadotrophin (HCG) pregnancy test documented within 7 days prior to IP initiation. 9. Women of childbearing potential and sexually active male patients must agree to use two reliable methods of contraception i.e., oral contraceptives, double barrier methods, hormonal injectable, transdermal, or implanted contraceptives, intrauterine device (IUD), tubal ligation, or vasectomy of their sexual partner(s) for > 30 days before Screening and up to 90 days after discontinuation of study treatment 10. Male subjects with female partners of child-bearing potential must agree to meet 1 of the following contraception for > 30 days before Screening and up to 90 days after discontinuation of study treatment. • Documentation of successful vasectomy or azoospermia. • Male condom plus partner use of 1 of the contraceptive options listed above for contraception for WOCBP (oral contraceptives, hormonal injectable, transdermal, or implanted contraceptives, IUD, tubal ligation) • Male subjects must also agree not to donate sperm up to 90 days after discontinuation of study treatment 11. Female patients without childbearing potential (spontaneous amenorrhea for > 12 months or surgically sterilised by tubal ligation, hysterectomy, or bilateral oophorectomy > 6 months before Screening) are eligible for inclusion without contraceptive use restriction 12. Female patients must agree not to restart breastfeeding until at least 6 months after last IP administration 13. Patients agrees not to participate in another interventional study while participating in the present clinical study 14. If receiving glucocorticoid therapy, the dose must be stable (or decreasing) over at least 7 days prior to commencing IP 15. Able to undergo gadolinium-enhanced magnetic resonance imaging (Gd-MRI) scans 16. Patients must be competent to understand the nature of the study and capable of giving written informed consent. Patients who understand the nature of the study but are unable to sign may have their next of kin provide written consent 17. A known molecular pathological finding related to prognosis of GBM (e.g. O-6-methylguanine-DNA methyltransferase [MGMT] methylation status; Isocitrate dehydrogenase 1 [IDH-1) mutation) or any other molecular pathology.
Exclusion criteria
1. Presence of leptomeningeal disease 2. Patients with documented history of human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) 3. Active autoimmune disorder or known history of an autoimmune neurologic condition (e.g. Guillain-Barre syndrome). Patients with vitiligo, type 1 diabetes mellitus, hypothyroidism due to autoimmune condition only requiring hormone replacement therapy, psoriasis not requiring systemic therapy, or conditions not expected to recur in the absence of an external trigger are permitted to enrol 4. Female patients who have been pregnant within the 6 months prior to Screening or breastfeeding within the 3 months prior to Screening 5. Patients with ECG evidence of a QTcF > 450 ms in men and > 470 ms in women and patients with any other risk factors for torsade de pointes (TdP) (such as hypokalaemia, hypomagnesaemia or hypocalcaemia or family history of long QT syndrome) 6. Patients with uncontrolled cardiac disease (e.g. uncontrolled hypertension: diastolic blood pressure [DBP] >100 mmHg, or systolic blood pressure [SBP] >180 mmHg) 7. Myocardial infarction within 6 months before enrolment, unstable angina, New York Heart Association (NYHA) class III or greater congestive heart failure, history of uncontrolled seizures, oxygen dependent chronic diseases, and active psychiatric disorder 8. Stroke or transient ischaemic attack within 6 months before enrolment 9. Clinically significant chronic obstructive pulmonary disease or uncontrolled asthma 10. A history of other malignancies, except adequately treated non-melanoma skin cancer, curatively treated in-situ cancer or other solid tumours curatively treated with no evidence of disease for = 2 years 11. Patients with known or suspected to have hypersensitivities, allergies to sodium meta arsenite, related compounds or any of the excipients of the IP 12. Unresolved toxicity > Grade 2, using Common Terminology Criteria for Adverse Events (CTCAE), attributed to any prior therapies (excluding haemoglobin, alopecia, pigmentation, and chemotherapy-induced neurotoxicity) 13. Patients with use of doses of paracetamol in excess of 4 g/day over the 6 months prior to Screening, or with severe malnutrition which may lead to glutathione depletion 14. Current anticoagulant or antiplatelet therapy, except for prophylactic doses of low molecular weight heparins or low-dose aspirin 15. Patients with an inability to comply with study procedures or any condition which in the Investigator's opinion makes the patient unsuitable for study participation 16. Patients with a psychiatric illness who the Investigator deems will have difficulty adhering to the study requirements 17. History of psychotic symptoms requiring antipsychotic treatment or history of a suicidal attempt/s within the prior 6 months 18. History or evidence of any other clinically significant condition including post-operative complications that, in the opinion of the Investigator, would pose a risk to patient safety or interfere with study procedures, evaluation or completion 19. Subjects with pseudoprogression will be excluded based upon imaging and the opinion from the Investigator.
Outcome results
None listed