The purpose of this study is to determine whether AZD0156 is safe, what is the best dose to give, and how it is processed by the body when given alone or in combination with other agents. The study will also collect some initial information about how effective it is.
The study will consist of a number of study modules, each evaluating the safety and tolerability of AZD0156 with a specific combination agent. The combination option may require an initial monotherapy dose escalation to gain an understanding of pharmacokinetics, safety and tolerability before initiating dose escalation in combination. An oral formulation of AZD0156 will be used. Module 1 explores AZD0156 in combination with olaparib Module 2 explores AZD0156 in combination with irinotecan/FOLFIRI Additional modules may be added to explore AZD0156 as a monotherapy or in combination with other agents and may be in different tumour types. Expansion cohorts may enroll additional patients to explore further the safety, tolerability, pharmacokinetics and biological activity at selected dose(s) or alternate dosing schedules, and to get a preliminary assessment of efficacy . Module 1 includes an expansion cohort in locally advanced/metastatic tumours including but not limited to gastric adenocarcinoma Module 2 includes an expansion cohort in colorectal cancer
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
84
All patients will receive AZD0156 as a monotherapy or in combination to assess safety and tolerability.
Module 1 combination with olaparib
Module 2 combination with irinotecan/FOLFIRI
Research Site
Aurora, Colorado, United States
Research Site
New York, New York, United States
Research Site
Seoul, South Korea
Research Site
Barcelona, Spain
Research Site
Safety and tolerability - Number of patients experiencing adverse events
Safety and tolerability of AZD0156 alone or in combination with either olaparib, cytotoxic chemotherapies, or novel anti-cancer agents as assessed through collection of Adverse Event, Serious Adverse Event, Clinical Chemistry/Haematology/Coagulation/Vital Signs and ECG
Time frame: Informed consent until end of Safety Follow-up (approximately 6 months)
Anti-tumour activity assessed through tumour measurements
Preliminary assessment of the anti-tumour activity of AZD0156 either as monotherapy alone or in combination with either olaparib, cytotoxic chemotherapies, or novel anti-cancer agents by evaluation of tumour response objective response rate using RECIST version 1.1
Time frame: Baseline and then every 6 weeks until Safety follow-up (approximately 6 months)
Changes in expression levels of proteins that may be impacted by ATM protein activity or inhibition
To obtain a preliminary assessment of AZD0156 activity in the tumour by evaluation of pharmacodynamic biomarker changes
Time frame: From baseline until 21 days of combination therapy (Approximately 11 assessments)
Changes in the number of CTCs (Circulating Tumour Cells)
To obtain a preliminary assessment of AZD0156 activity in the tumour by evaluation of the total amount of circulating tumour cells (CTCs)
Time frame: From baseline until 21 days of combination therapy (Approx 6 assessments)
Changes in the level of total ctDNA (Circulating tumour DNA)
To obtain a preliminary assessment of AZD0156 activity in the tumour by evaluation of the total amount of ct DNA
Time frame: From baseline until 21 days of combination therapy (approximately 11 assessments)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Module 2 combination with irinotecan/FOLFIRI
Module 2 combination with irinotecan/FOLFIRI
Manchester, United Kingdom
Measure maximum plasma concentration (Cmax)
Measurement of Cmax as part of pharmacokinetic assessment
Time frame: From Baseline until 31 days into combination treatment (maximum of 52 timepoints)
Measure maximum plasma concentration at steady state (Css max)
Measurement of Css max as part of pharmacokinetic assessment
Time frame: From Baseline until 31 days into combination treatment (maximum of 52 timepoints)
Measure time to maximum concentration (tmax)
Measurement of tmax as part of pharmacokinetic assessment
Time frame: From Baseline until 31 days into combination treatment (maximum of 52 timepoints)
Measure time to maximum concentration at steady state (tss max)
Measurement of tss max as part of pharmacokinetic assessments
Time frame: From Baseline until 31 days into combination treatment (maximum of 52 timepoints)
Measurement of exposure by AUC (Area Under the Curve) calculation
Measurement of AUC as part of pharmacokinetic assessment
Time frame: From Baseline until 31 days into combination treatment (maximum of 52 timepoints)
Measure minimum concentration at steady state (Css min)
Measurement of Css min as part of pharmacokinetic assessment
Time frame: From Baseline until 31 days into combination treatment (maximum of 52 timepoints)
Measure rate of renal clearance (CLR)
Measurement of renal clearance (CLR) as part of pharmacokinetic assessment
Time frame: From Baseline until 7 days into treatment period
Measure drug accumulation in the body (RAC)
Measurement of RAC as part of pharmacokinetic assessments
Time frame: From Baseline until 31 days into combination treatment (maximum of 52 timepoints)
Identification of Maximum Tolerated Dose (MTD)
Safety and tolerability of AZD0156 alone or in combination with cytotoxic chemotherapies or novel anti-cancer agents as assessed through collection of Adverse Events
Time frame: Informed consent untli end of Dose Limiting Toxicity (DLT) period - Approx 1 month
Overall Survival (Part B Only)
Period of time from the start of treatment until end of life from any cause
Time frame: From start of treatment until the end of Long Term Follow-up (Approx 12 months)