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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-002572-25 | EudraCT Number |
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| Name | Class |
|---|---|
| Syneos Health | OTHER |
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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Safety and Tolerability | Experimental | 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 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZD0156 | Drug | All patients will receive AZD0156 as a monotherapy or in combination to assess safety and tolerability. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 | Informed consent until end of Safety Follow-up (approximately 6 months) |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Baseline and then every 6 weeks until Safety follow-up (approximately 6 months) |
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Inclusion criteria for all parts of the study
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| Name | Affiliation | Role |
|---|---|---|
| Matthew Krebs, BMedSci, BM, BS, PhD, MRCP | The Christie Hospital, Manchester, UK | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Aurora | Colorado | 80045 | United States | ||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34904813 | Derived | Smith G, Alholm Z, Coleman RL, Monk BJ. DNA Damage Repair Inhibitors-Combination Therapies. Cancer J. 2021 Nov-Dec 01;27(6):501-505. doi: 10.1097/PPO.0000000000000561. | |
| 31534013 | Derived | Riches LC, Trinidad AG, Hughes G, Jones GN, Hughes AM, Thomason AG, Gavine P, Cui A, Ling S, Stott J, Clark R, Peel S, Gill P, Goodwin LM, Smith A, Pike KG, Barlaam B, Pass M, O'Connor MJ, Smith G, Cadogan EB. Pharmacology of the ATM Inhibitor AZD0156: Potentiation of Irradiation and Olaparib Responses Preclinically. Mol Cancer Ther. 2020 Jan;19(1):13-25. doi: 10.1158/1535-7163.MCT-18-1394. Epub 2019 Sep 18. |
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Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
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| Olaparib | Drug | Module 1 combination with olaparib |
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| irinotecan | Drug | Module 2 combination with irinotecan/FOLFIRI |
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| Fluorouracil | Drug | Module 2 combination with irinotecan/FOLFIRI |
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| Folinic Acid | Drug | Module 2 combination with irinotecan/FOLFIRI |
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| 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 | 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) | 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 | From baseline until 21 days of combination therapy (approximately 11 assessments) |
| Measure maximum plasma concentration (Cmax) | Measurement of Cmax as part of pharmacokinetic assessment | 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 | 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 | 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 | 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 | 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 | 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 | From Baseline until 7 days into treatment period |
| Measure drug accumulation in the body (RAC) | Measurement of RAC as part of pharmacokinetic assessments | 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 | 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 | From start of treatment until the end of Long Term Follow-up (Approx 12 months) |
| New York |
| New York |
| 10033 |
| United States |
| Research Site | Seoul | 03080 | South Korea |
| Research Site | Barcelona | 08035 | Spain |
| Research Site | Manchester | M20 4BX | United Kingdom |
| ID | Term |
|---|---|
| C000631425 | AZD0156 |
| C531550 | olaparib |
| D000077146 | Irinotecan |
| D005472 | Fluorouracil |
| D002955 | Leucovorin |
| ID | Term |
|---|---|
| D002166 | Camptothecin |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D005575 | Formyltetrahydrofolates |
| D013763 | Tetrahydrofolates |
| D005492 | Folic Acid |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D003067 | Coenzymes |
| D045762 | Enzymes and Coenzymes |
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