None listed
Conditions
Brief summary
This is a Phase I, open-label, single arm, safety and tolerability study which will evaluate escalating dose cohorts of ATX-101 to determine the maximum tolerated dose in subjects with advanced solid tumours. Who is it for? You may be eligible to join this study if you are aged 18 years or above, have advanced solid tumours for which conventional anti-tumour treatment has been exhausted or has been refused Study details The study is designed to systematically assess safety and tolerability, and to identify the maximum tolerated dose (MTD) for ATX-101. Dose escalation will be determined based on recommendations from a Safety Review Committee and is expected to occur over a total of 6 cohorts. Potential study subjects who provide voluntary written informed consent will undergo screening evaluations to determine eligibility within 28 days prior to enrolment and the start of treatment (Day 1). Eligible subjects will be admitted to the study centre on Day 1 for the first dose of study drug to be administered by IV infusion. Prior to each treatment infusion the subject will receive mandated pre-medication. Treatment will be administered weekly in cycles of 21-day duration, with a single IV infusion of ATX-101 on Day 1, 8 and 15. Dosing of subjects will occur weekly for up to two cycles (i.e. 2 x 21 days = 6 weeks), or until criteria for early termination is met. After completion of the end of study visit, subjects without documented progressive disease may be approved to continue weekly treatment under a separate long term follow up protocol (AM ATX101-02). Under Protocol AM ATX-101-02, subjects are to be monitored by tumour imaging every 3 months (± 14 days) until documentation of progressive disease.
Interventions
ATX-101 treatment will be administered weekly, as a single Intravenous Infusion (IV).
All subjects will receive mandated premedication with a corticosteroid, and H1 and H2 inhibitors 60 to 90 minutes prior to every dose of ATX-101 as follows:
• Dexamethasone 12 mg IV (or pharmacologically equivalent corticosteroid at an equivalent dose)
• Phenergan 12.5 mg IV (or pharmacologically alternative i.e. promethazine at recommended dose)
• Ranitidine 150 mg orally of Famotidine 20 mg orally
• Acetami
ATX-101 treatment will be administered weekly, as a single Intravenous Infusion (IV). All subjects will receive mandated premedication with a corticosteroid, and H1 and H2 inhibitors 60 to 90 minutes prior to every dose of ATX-101 as follows: • Dexamethasone 12 mg IV (or pharmacologically equivalent corticosteroid at an equivalent dose) • Phenergan 12.5 mg IV (or pharmacologically alternative i.e. promethazine at recommended dose) • Ranitidine 150 mg orally of Famotidine 20 mg orally • Acetaminophen 1 g oral Dosing will occur weekly for up to 2 cycles (i.e. 2 x 21 days = 6 weeks), on days 1, 8 and 15 (cycle 1) and days 22. 29 and 36 (cycle 2). Cohort 1 is to start at a dose level of 20mg/m2. The dose escalation scheme, as overseen by a safety monitoring committee (SMC), will be followed, with up to 6 Cohorts expected. The SMC will provide expert recommendation on dose levels adjustments for subsequent cohorts. Current planned doses for subsequent cohorts: Cohort 2: 30 mg/m2 Cohort 3: 45 mg/m2 Cohort 4: 60 mg/m2 Cohort 5: 90 mg/m2 Cohort 6: 135 mg/m2 Any additional cohort: TBD (up to 450 mg/m2) After completion of the end of study visit, subjects without documented progressive disease may be approved to continue weekly treatment under as separate long term follow up protocol (AM ATX101-02). Under Protocol AM ATX-101-02, subjects are to be monitored by tumour imaging every 3 months (± 14 days) until documentation of progressive disease.
Sponsors
Therapim Pty Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
- Advanced disease (solid tumour) for which conventional anti-tumour treatment has been exhausted or has been refused - Measurable or non-measurable (but radiologically evaluable) disease on CT/MRI scan with at least one lesion outside previously irradiated areas - Have an ECOG Performance status 0-2 - Life expectancy of at least 3 months - Meet the following laboratory requirements: Absolute lymphocyte count greater than or equal 0.8 x 109/L Platelet count greater than or equal 75 x 109/L Activated partial thromboplastin time (aPTT)/prothrombin time (PT) less than or equal to 1.5 x the upper limit of normal (ULN) Total bilirubin level less than or equal to 1.5 x ULN Aspartate transaminase (AST) and Alanine Aminotransferase (ALT) less than or equal to 2.5 x ULN (less than or equal to 5 x ULN if liver metastasis present) Creatinine less than or equal to 1.5 x ULN Albumin greater than or equal to 30 g/L
Exclusion criteria
1. Have received an investigational drug within 4 weeks 2. Concurrent anticancer treatment within 21 days or 5x (five times) their half-lives (whichever is shorter) before the first dose of trial treatment 3. Use of hormonal agents within 7 days before start of trial treatment, except for subjects with castration-resistant prostate cancer (CRPC), who may remain on treatment with luteinizing hormone–releasing hormone agonists or antagonists a. Note: Subjects receiving bisphosphonate or denosumab are eligible provided that treatment was initiated more or equal to 14 days before first dose of treatment. 4. Anticipated requirement for surgery or initiation of anti-cancer therapy during the study period 5. Have not recovered from AEs (more or equal to CTCAE Grade 2 other than alopecia) due to agent(s) administered more than 4 weeks earlier 6. Cardiac failure (per New York Heart Association [NYHA] functional classification) of more than Grade 2. 7. Evidence or history of clinically significant cardiac disease including congestive heart failure, unstable angina, acute myocardial infarction or cerebrovascular accident within the last six months, and symptomatic arrhythmia requiring therapy (with the exception of extra systoles or minor conduction abnormalities and controlled and well-treated chronic atrial fibrillation). 8. QTcF more than 460 ms 9. Active central nervous system (CNS) metastases. Subjects with known CNS metastases must have received previous radiotherapy or surgery at least two weeks prior to receiving ATX-101. Any residual neurological deficit must be stable off corticosteroids. 10. Lymphangitic carcinomatosis 11. Leptomeningeal involvement 12. Major surgery within 3 weeks of screening 13. Current acute or chronic disease, other than the study indication, that would increase the expected risk of exposure to the investigational product or would be expected to interfere with the planned evaluations, in the judgment of the Investigator 14. Breastfeeding or pregnant as confirmed by a positive serum beta human chorionic gonadotropin (ß-HCG) pregnancy test at screening or at subsequent clinic visits 15. Unwilling or unable to follow protocol requirements 16. Known positive status of Human immunodeficiency virus (HIV) and/or active Hepatitis B or C. In subjects with a history of Hepatitis B or Hepatitis C infection, resolution of infection must be demonstrated by negative serology for Hepatitis B surface antigen (HBsAg) and Hepatitis C virus (HCV) ribonucleic acid (RNA) must be demonstrated at least 6 weeks following antiviral therapy. 17. History of severe allergy (requiring hospital care), severe reaction to any drug, or any known or suspected allergies or sensitivities to the study drug constituents. 18. Inadequate venous access to allow collection of blood samples.
Outcome results
None listed