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Trial registered on ANZCTR


Registration number
ACTRN12619000640101
Ethics application status
Approved
Date submitted
12/04/2019
Date registered
30/04/2019
Date last updated
13/12/2019
Date data sharing statement initially provided
30/04/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A study of PAX-1 in combination with standard of care treatment in patients with newly diagnosed or recurrent glioblastoma
Scientific title
A Phase 2, open-label study of orally administered PAX-1 in combination with standard of care treatment in patients with newly diagnosed or recurrent glioblastoma
Secondary ID [1] 297965 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Glioblastoma 312371 0
Condition category
Condition code
Cancer 310928 310928 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental therapy: PAX-1 (sodium meta-arsenite tablets)

Arm 1: Newly diagnosed glioblastoma
Arm 2: Recurrent glioblastoma

Patients will receive a daily 15 mg oral dose of PAX-1 in a combination with investigator choice of standard of care until disease progression, patients withdraw due to tolerability, or patients withdraw consent.

All patients will be required to bring their unused study medication and empty containers at the end of each cycle to enable monitoring of patient compliance. Patients will also be telephoned in-between visits during the first two treatment cycles to check for compliance issues.
Intervention code [1] 314185 0
Treatment: Drugs
Comparator / control treatment
No control group. Each arm will be compared against historical data generated at the lead clinical trial site over the past 5 years.
Control group
Historical

Outcomes
Primary outcome [1] 319744 0
Median progression free survival using RANO (radiographic assessment in neuro-oncology) Response Criteria
Timepoint [1] 319744 0
Patients will be assessed every 8 weeks until progression or death
Secondary outcome [1] 369383 0
Progression Free Survival (12 months). PFS shall be defined as the time from baseline MRI scan until objective tumour progression or death using RANO criteria.
Timepoint [1] 369383 0
12 months. Patients will be evaluated every 8 weeks. Confirmatory scans should be obtained not less than 4 weeks following initial documentation of an objective response.
Secondary outcome [2] 369384 0
Overall survival
Timepoint [2] 369384 0
From date of baseline MRI scan to death (last day of follow-up will be the 12 months from the date the last patient was enrolled in the study).
Secondary outcome [3] 369385 0
Safety and tolerability of PAX-1 in combination with standard of care.

The safety and tolerability of PAX-1 will be evaluated from the incidence of treatment emergent Adverse Events, results of reported signs and symptoms, scheduled physical examinations, vital sign measurements, and clinical laboratory test results.
Timepoint [3] 369385 0
For the duration of the study. Patient will remain on study until they experience confirmed disease progression, are withdrawn due to tolerability, or they withdraw consent

Eligibility
Key inclusion criteria
1. Evidence of glioblastoma: Cohort A: histologically proven diagnosis of glioblastoma; Cohort B: Recurrent Glioblastoma: histologically proven diagnosis of glioblastoma and previously been treated with external beam radiation and temozolomide chemotherapy
2. Patients who are either candidates for resection (complete, or partial resulting in a <1 cm lesion on enhancement) or if not a candidate for resection have a < 1 cm lesion on enhancement
3. Male or female patients between 18 years of age and <70 years of age
4. ECOG status 0-2
5. Adequate organ function: ANC >1.5 x10^9/L, platelet count >100x10^9/L, haemoglobin >90g/L, total bilirubin < 1.5 upper limit of normal (ULN) (< 2.5 ULN if patient has Gilbert’s syndrome), AST/ALT not more than 2.5 x ULN; not more than 5 x ULN for patients with liver metastases, normal serum creatinine or calculated creatinine clearance >50ml/min, albumin >24g/L, INR and APTT <1.5 ULN, serum magnesium > 0.9mmol/L, serum potassium > 4.0mmol/L, serum electrolyte levels within normal range or deemed not clinically significant by the Investigator
6. Able to take oral medication
7. Women of childbearing potential must have a negative serum beta-HCG pregnancy test documented within 7 days prior to study drug initiation
8. 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, tubal ligation, or vasectomy of their sexual partner(s) for > 30 days before screening and up to 90 days after discontinuation of study treatment
9. Female patients without childbearing potential (spontaneous amenorrhea for > 12 months or surgically sterilized by tubal ligation, hysterectomy, or bilateral oophorectomy > 6 months before Screening) are eligible for inclusion without contraceptive use restriction
10. Female patients must agree not to breastfeed starting at screening and continuing throughout the clinical study period, and for 6 months after last study drug administration
11. Patients agrees not to participate in another interventional study while participating in the present clinical study
12. If receiving glucocorticoid therapy, the dose must be stable (or decreasing) over at least 7 days prior to commencing study drug
13. Able to undergo gadolinium-enhanced MRI (Gd-MRI) scans
14. Patients must be competent to understand the nature of the study & 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.
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Presence of leptomeningeal disease
2. Patients with documented history of HIV or 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 enroll
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 greater than 450 milliseconds in men and greater than 470 milliseconds in women and patients with any other risk factors for torsade de pointes (such as hypokalaemia, hypomagnesemia or hypocalcaemia or family history of long QT syndrome)
6. Patients with uncontrolled cardiac disease (e.g. uncontrolled hypertension (diastolic blood pressure >100, or systolic blood pressure >180)
7. Myocardial infarction within 6 months before enrolment, unstable angina, New York Heart Association class III or greater congestive heart failure, history of uncontrolled seizures, oxygen dependent chronic diseases, and active psychiatric disorder
8. Stroke or transient ischemic attack within 6 months before enrolment
9. Clinically significant chronic obstructive pulmonary disease or 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 more than or equal to 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 study drug (see protocol for details)
12. Unresolved toxicity grater than or equal to Grade 2, using Common Terminology Criteria for Adverse Events (CTCAE), attributed to any prior therapies (excluding haemoglobin, alopecia, pigmentation, and chemotherapy-induced neurotoxicity)
13. Treatment with bevacizumab (Avastin) within 3 months of enrolment or planned treatment with bevacizumab while on study
14. Patients with prolonged use of chronic supratherapeutic doses of paracetamol in excess of 4g/day or with severe malnutrition which may lead to glutathione depletion.
15. Current anticoagulant or antiplatelet therapy, except for prophylactic doses of low molecular weight heparins or low-dose aspirin.
16. 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
17. History or evidence of any other clinically-significant condition that, in the opinion of the investigator, would pose a risk to patient safety or interfere with study procedures, evaluation or completion.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 15105 0
Prince of Wales Private Hospital - Randwick
Recruitment postcode(s) [1] 28400 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 302484 0
Commercial sector/Industry
Name [1] 302484 0
Komipharm International Australia
Address [1] 302484 0
11 Monterey Rd Dandenong South Victoria 3175
Country [1] 302484 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Novotech (Australia) Pty Limited
Address
Level 3, 235 Pyrmont Street, Pyrmont NSW 2009
Country
Australia
Secondary sponsor category [1] 302383 0
None
Name [1] 302383 0
Address [1] 302383 0
Country [1] 302383 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303146 0
South Eastern Sydney Local Health District HREC
Ethics committee address [1] 303146 0
Prince of Wales Hospital, Randwick NSW 2031
Ethics committee country [1] 303146 0
Australia
Date submitted for ethics approval [1] 303146 0
16/01/2019
Approval date [1] 303146 0
16/08/2019
Ethics approval number [1] 303146 0
2019/ETH00016

Summary
Brief summary
The purpose of this study is to assess whether the drug PAX-1 can delay cancer progression in patients with either newly diagnosed gliomblastoma or glioblastoma that has reoccurred, when given with standard therapies.

Who is it for?
You may be eligible for this study if you are aged 18 to 70, and have newly diagnosed or recurrent glioblastoma.

Study details
Participants will be assigned to two groups, either newly diagnosed or recurrent glioblastoma. Patients will receive a daily 15 mg oral dose of PAX-1 in a combination with their doctors choice of standard of care until disease progression, patients withdraw due to tolerability, or they withdraw consent. 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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 92634 0
Prof Charlie Teo
Address 92634 0
Prince of Wales Private Hospital, Barker Street, Randwick, NSW, 2031
Country 92634 0
Australia
Phone 92634 0
+61 (0)296504940
Fax 92634 0
Email 92634 0
laine@neuroendoscopy.info
Contact person for public queries
Name 92635 0
Mr Samuel Lee
Address 92635 0
Komipharm International Australia 11 Monterey Road, Dandenong South, Victoria,3175,
Country 92635 0
Australia
Phone 92635 0
+61 430 441 622
Fax 92635 0
Email 92635 0
samuel.lee@komipharm.com.au
Contact person for scientific queries
Name 92636 0
Mr Samuel Lee
Address 92636 0
Komipharm International Australia 11 Monterey Road, Dandenong South, Victoria,3175,
Country 92636 0
Australia
Phone 92636 0
+61430441622
Fax 92636 0
Email 92636 0
samuel.lee@komipharm.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Clinical trial data for this study is confidential. The Sponsor will use the data for publication purposes and regulatory activities but not share IPD publicly.
What supporting documents are/will be available?
No other documents available
Summary results
No Results