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Trial registered on ANZCTR


Registration number
ACTRN12621000093886
Ethics application status
Approved
Date submitted
16/09/2020
Date registered
1/02/2021
Date last updated
1/02/2021
Date data sharing statement initially provided
1/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 2 clinical trial to assess the safety and efficacy of ACT001 in combination with whole brain radiation therapy (WBRT) for participants with brain metastases from solid tumours.
Scientific title
A Phase 2, open label, multicentre study assessing the safety and efficacy of ACT001 in combination with whole brain radiation therapy (WBRT) for brain metastases from solid tumours.
Secondary ID [1] 302118 0
ACT001-AU-004
Universal Trial Number (UTN)
U1111-1257-3677
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Brain Cancer 318745 0
Solid Tumours 319399 0
Condition category
Condition code
Cancer 316763 316763 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
An open label study using 400 milligrams (mg) of ACT001 oral capsule taken twice daily (total dose 800mg per day) in combination with standard of care whole brain radiation therapy in the setting of brain metastases from solid tumours including metastases from: Non Small Cell Lung Carcinoma (NSCLC), breast, urogenital, head and neck, hepatocellular, melanoma and colorectal cancers.
Drug return will be used to monitor adherence

400mg of ACT001 will be administered orally, twice a day, for 2 weeks (14 days) prior to commencement of Whole Brain Radiation Therapy (WBRT), and continue the study drug until the end of Week 18 (study drug will be taken for up to 126 days total if patient maintains good health and does not require additional follow on therapy post-WBRT).
Intervention code [1] 318420 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 324885 0
To assess the safety and tolerability of 800mg of ACT001 per day given as 400mg twice daily regimen in combination with whole brain radiation therapy for brain metastases from solid tumours
Assessed by Incidence and grades of Adverse events (All grades AE) and clinical examinations
Timepoint [1] 324885 0
Incidence of Adverse events (All grades AE) from Day 0 of study treatment, weeks 2, 4, 6, 10, 12, 18, 26, 34 and 42


Primary outcome [2] 324886 0
To assess the tissue protective efficacy of ACT001 assessed using Radiation Therapy Oncology Group (RTOG) advanced brain injury grade and Neurotoxicity grade (According to Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0) (composite outcome).
Timepoint [2] 324886 0
Radiation Therapy Oncology Group (RTOG) advance brain injury grade from pre-dose on Day 0 until the end of study (Week 42)

Neurotoxicity grade (According to Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0) from pre-dose on Day 0 until the end of study (week 42)
Primary outcome [3] 325604 0
Change from baseline of the European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC QLQ-C30) and EORTC QLQ Brain Cancer module scores from pre-dose on Day 0 until the end of study (week 42).
Timepoint [3] 325604 0
From Pre-dose on Day 0 until the end of study (week 42)
Secondary outcome [1] 386097 0
To assess the effect on corticosteroid requirements in the setting of WBRT from brain metastases from solid tumours assessed from hospital records and patient report at each visit
Timepoint [1] 386097 0
Change from baseline in corticosteroid requirements from pre-dose on Day 0 until the end of study (week 42)
Secondary outcome [2] 386099 0
Clinical efficacy (assessed as a composite of objective response rate, progression free survival and long term assessment of QoL and function) of ACT001 on brain metastases from solid tumours
Timepoint [2] 386099 0
Objective Response Rate (ORR) according to RANO-BM criteria 14 weeks post completion of WBRT

Progression free survival (PFS) of intracranial tumours according to RANO-BM criteria 14 weeks post completion of WBRT

QoL and function will be assessed by EORTC QLQ-C30

Long term assessment for QoL and function to be followed for 10 months post completion of WBRT

Eligibility
Key inclusion criteria
1. Patients with secondary brain metastases from solid tumours including NSCLC, breast, urogenital, head and neck, hepatocellular, melanoma and colorectal cancers. Definitive diagnosis of the primary site tumour by histology/cytology or molecular pathology;
2. Participants that are assessed by the investigator to be suitable for WBRT;
3. At least 1 measurable lesion according to RANO-BM criteria (verified by the radiologist and clinician), with a diameter of the lesion should be >/=10mm < /=40 mm;
4. No previous history of abnormal bleeding and coagulation function International Normalised Ratio (INR) < /= 2;
5. Age >/= 18 years
6. Normal organ function (Absolute Neutrophil Count (ANC) >/=1.5 × 109/L, lymphocyte count >/= 0.5×109/L, platelet count >/= 75×109/L, Haemoglobin (Hb) >/= 10 g/dl; total Bilirubin < /= 1.5 x upper limit of normal (ULN); Alanine Aminotransferase (ALT) and Aspartate aminotransferase (AST) < /= 2.5 x ULN [if liver metastases are present < /= 5.0 x ULN]; plasma creatinine < /= 1.5 x ULN; QTc < 450 ms [males], < 470 ms [females];
7. Life expectancy of at least 6 months
8. Female participants must also fulfill the following criteria before enrolment can be considered: • Of non-childbearing potential, defined as:
Previous hysterectomy or bilateral oophorectomy,
or Previous bilateral tubal ligation,
or Menopause (total cessation of menses for >/= 1 year).
Of childbearing potential, but serum pregnancy test was negative during screening (within 7 days prior to the first dose of the investigational drug.) and agrees to employ contraceptive measures (such as intrauterine device, contraceptive drugs, or condoms) that are medically recognized before enrolment and during the study until 30 days after the last dose of the investigational drug.
9. Male patients who are sexually active must agree to employ barrier contraceptive measures or complete abstinence.
10. Agrees to sign the informed consent form before study enrolment.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Past history of brain radiotherapy.
2. Participants with uncontrollable infection (systemic infection within 4 weeks prior to enrolment).
3. Suffered from malignancies other than the primary tumour within 5 years prior to screening (except for cervical carcinoma in situ, basal cell carcinoma or squamous cell carcinoma of the skin, local prostate cancer after radical surgery, and ductal carcinoma in situ).
4. Participants previously diagnosed with small cell lung carcinoma (SCLC) with brain metastases
5. Participants requiring continuous administration of hematopoietic factors (including granulocyte colony-stimulating factor, macrophage colony-stimulating factor) or platelet transfusion to maintain platelet count and absolute neutrophil count.
6. Participants with severe heart disease before enrolment, such as unstable angina pectoris, myocardial infarction, heart failure (New York Heart Association Class > II) or stroke (except for lacunar infarction).
7. Patients with hypertension that cannot be controlled by drugs (systolic blood pressure over or equal to 160 mmHg, diastolic blood pressure over or equal to 100 mmHg after taking anti-hypertensive medications).
8. Patients who are unable to take the drug orally or have malabsorption syndrome.
9. Presence of epilepsy and/or elevated intracranial pressure that is refractory to drugs.
10. Uncontrollable spinal cord compression
11. Active cerebral haemorrhage in CT/MRI examinations.
12. Known allergy to ACT001 or similar compounds or any component in the ACT001 formulation.
13. Patients who received other anti-tumour treatment for brain metastases of solid tumours within 4 weeks prior to ACT001 treatment, such as chemotherapy, biologic therapy or targeted therapy, immunotherapy, radiotherapy, or electric field therapy.
14. Toxicity caused by past anti-tumour treatment that has not been resolved, which is defined as: Toxicity that did not resolved to Grade < 2 according to CTCAE V 5.0 criteria (except for alopecia, alkaline phosphatase, and gamma-glutamyl transferase (GGT). Stable toxicity may be allowed after discussion with the investigator and sponsor.
15. Pregnant or lactating women.
16. Patients who participated in other clinical trials within 4 weeks prior to screening.
17. Other reasons that are deemed unsuitable for participation in this trial by the investigator

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
This sample size has been assigned empirically.

Descriptive statistics (number of participants, mean, median, standard deviation, minimum, and maximum) will be used to summarize continuous variables. Frequency and percentage will be used to summarize categorical variables. The analysis set includes the safety analysis set and clinical efficacy analysis set.

Recruitment
Recruitment status
Not yet 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)
VIC
Recruitment hospital [1] 17324 0
Epworth Richmond - Richmond
Recruitment postcode(s) [1] 31050 0
3121 - Richmond

Funding & Sponsors
Funding source category [1] 306539 0
Commercial sector/Industry
Name [1] 306539 0
Accendatech Au Pty Ltd
Address [1] 306539 0
Suite 2903,
201 Elizabeth Street Sydney
NSW 2000
Country [1] 306539 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Accendatech Au Pty Ltd
Address
Suite 2903,
201 Elizabeth Street Sydney
NSW 2000
Country
Australia
Secondary sponsor category [1] 307072 0
None
Name [1] 307072 0
Address [1] 307072 0
Country [1] 307072 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306735 0
Bellberry Limited
Ethics committee address [1] 306735 0
123 Glen Osmond Rd, Eastwood SA 5063
Ethics committee country [1] 306735 0
Australia
Date submitted for ethics approval [1] 306735 0
05/10/2020
Approval date [1] 306735 0
22/12/2020
Ethics approval number [1] 306735 0
69120

Summary
Brief summary
This study will evaluate the safety and tolerability of ACT001 in combination with standard of care whole brain radiation therapy for patients with metastatic brain cancer (cancer that has spread to the brain from another body part).

Who is it for?
You may be eligible for this study if you are aged 18 or older, you have been diagnosed with secondary brain metastases (cancer lesions that have spread to the brain) from solid tumours including non-small cell lung cancer, breast, urogenital, head and neck, hepatocellular, melanoma and colorectal cancers, and you are eligible to undergo whole brain radiation therapy.

Study details
Participants will be asked to take 4 oral capsules of the study drug-ACT001 twice a day for up to 18 weeks. Standard care whole brain radiation therapy sessions will be scheduled to start 2 weeks after the first dose of ACT001, participants will continue to self-administer the daily doses of ACT001 until the end of the 18 week study period. During the study participants will be asked to attend a study clinic to report any unexpected side effects they experience during the study, and to complete quality of life questionnaires. Additional doses of ACT001 will be given to participants during these visits so that they can continue to self-administer the drug at home. All participants who are enrolled in this study will be asked to undergo a pre-treatment MRI, followed by two post-treatment MRIs at week 10 and week 18.

It is hoped this research will demonstrate that ACT001 is safe and effective in treating patients with metastatic brain cancer, and is able to protect healthy cells during whole brain radiation therapy.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 104842 0
Dr Patrick Bowden
Address 104842 0
Epworth Centre, 32 Erin St, Richmond VIC 3121
Country 104842 0
Australia
Phone 104842 0
+61 3 9936 8277
Fax 104842 0
Email 104842 0
pat.bowden@icon.team
Contact person for public queries
Name 104843 0
Mr Greg Plunkett
Address 104843 0
Accelagen Pty Ltd
Suite 1.02, Level 1
722 High Street, Kew East
Victoria, Australia 3102
Country 104843 0
Australia
Phone 104843 0
+61 3 9114 2274
Fax 104843 0
Email 104843 0
greg.plunkett@accelagen.com.au
Contact person for scientific queries
Name 104844 0
Dr Doug Cai
Address 104844 0
Accendatech Au Pty Ltd
21 Strathmore Road
Natick, MA 01760, USA
Country 104844 0
United States of America
Phone 104844 0
+16 17 669 5138
Fax 104844 0
Email 104844 0
dongpo.cai@accendatech.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Study outcomes are reported as the total population, and not based on individual results.
What supporting documents are/will be available?
Clinical study report
How or where can supporting documents be obtained?
Type [1] 8918 0
Clinical study report
Citation [1] 8918 0
Link [1] 8918 0
Email [1] 8918 0
pat.bowden@icon.team
Other [1] 8918 0
Upon request from Principal Investigator (email: pat.bowden@icon.team)
Attachment [1] 8918 0
Summary results
No Results