Study to Assess the Safety and Preliminary Efficacy of AZD0156 at Increasing Doses Alone or in Combination With Other Anti-cancer Treatment in Patients With Advanced Cancer
- Conditions
- Advanced Solid Tumours
- Interventions
- Registration Number
- NCT02588105
- Lead Sponsor
- AstraZeneca
- Brief Summary
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.
- Detailed Description
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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 84
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Safety and Tolerability AZD0156 All patients will receive AZD0156 as a monotherapy or in combination with either olaparib, cytotoxic chemotherapies, or novel anti-cancer agents to assess safety and tolerability Safety and Tolerability irinotecan All patients will receive AZD0156 as a monotherapy or in combination with either olaparib, cytotoxic chemotherapies, or novel anti-cancer agents to assess safety and tolerability Safety and Tolerability Folinic Acid All patients will receive AZD0156 as a monotherapy or in combination with either olaparib, cytotoxic chemotherapies, or novel anti-cancer agents to assess safety and tolerability Safety and Tolerability Olaparib All patients will receive AZD0156 as a monotherapy or in combination with either olaparib, cytotoxic chemotherapies, or novel anti-cancer agents to assess safety and tolerability Safety and Tolerability Fluorouracil All patients will receive AZD0156 as a monotherapy or in combination with either olaparib, cytotoxic chemotherapies, or novel anti-cancer agents to assess safety and tolerability
- Primary Outcome Measures
Name Time Method Safety and tolerability - Number of patients experiencing adverse events Informed consent until end of Safety Follow-up (approximately 6 months) 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
- Secondary Outcome Measures
Name Time Method Changes in the number of CTCs (Circulating Tumour Cells) From baseline until 21 days of combination therapy (Approx 6 assessments) To obtain a preliminary assessment of AZD0156 activity in the tumour by evaluation of the total amount of circulating tumour cells (CTCs)
Measurement of exposure by AUC (Area Under the Curve) calculation From Baseline until 31 days into combination treatment (maximum of 52 timepoints) Measurement of AUC as part of pharmacokinetic assessment
Overall Survival (Part B Only) From start of treatment until the end of Long Term Follow-up (Approx 12 months) Period of time from the start of treatment until end of life from any cause
Anti-tumour activity assessed through tumour measurements Baseline and then every 6 weeks until Safety follow-up (approximately 6 months) 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
Changes in expression levels of proteins that may be impacted by ATM protein activity or inhibition From baseline until 21 days of combination therapy (Approximately 11 assessments) To obtain a preliminary assessment of AZD0156 activity in the tumour by evaluation of pharmacodynamic biomarker changes
Changes in the level of total ctDNA (Circulating tumour DNA) From baseline until 21 days of combination therapy (approximately 11 assessments) To obtain a preliminary assessment of AZD0156 activity in the tumour by evaluation of the total amount of ct DNA
Measure maximum plasma concentration at steady state (Css max) From Baseline until 31 days into combination treatment (maximum of 52 timepoints) Measurement of Css max as part of pharmacokinetic assessment
Measure time to maximum concentration (tmax) From Baseline until 31 days into combination treatment (maximum of 52 timepoints) Measurement of tmax as part of pharmacokinetic assessment
Measure time to maximum concentration at steady state (tss max) From Baseline until 31 days into combination treatment (maximum of 52 timepoints) Measurement of tss max as part of pharmacokinetic assessments
Measure rate of renal clearance (CLR) From Baseline until 7 days into treatment period Measurement of renal clearance (CLR) as part of pharmacokinetic assessment
Identification of Maximum Tolerated Dose (MTD) Informed consent untli end of Dose Limiting Toxicity (DLT) period - Approx 1 month Safety and tolerability of AZD0156 alone or in combination with cytotoxic chemotherapies or novel anti-cancer agents as assessed through collection of Adverse Events
Measure maximum plasma concentration (Cmax) From Baseline until 31 days into combination treatment (maximum of 52 timepoints) Measurement of Cmax as part of pharmacokinetic assessment
Measure minimum concentration at steady state (Css min) From Baseline until 31 days into combination treatment (maximum of 52 timepoints) Measurement of Css min as part of pharmacokinetic assessment
Measure drug accumulation in the body (RAC) From Baseline until 31 days into combination treatment (maximum of 52 timepoints) Measurement of RAC as part of pharmacokinetic assessments
Trial Locations
- Locations (1)
Research Site
🇬🇧Manchester, United Kingdom