A Phase I Trial of AZD3965 in Patients With Advanced Cancer
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|ClinicalTrials.gov Identifier: NCT01791595|
Recruitment Status : Recruiting
First Posted : February 15, 2013
Last Update Posted : September 10, 2019
The main aims of this clinical study are to find out the maximum dose that can be given safely to patients, the potential side effects of the drug and how they can be managed and what happens to AZD3965 inside the body.
AZD3965 is a type of drug called a monocarboxylate transporter 1 inhibitor which is being used to stop the growth of cancer cells and kill cancer cells by blocking the action of one of the proteins involved in moving chemical compounds in and out of the cells of the body. This will be the first time that this type of drug has been given to patients.
The drug is a capsule and is taken daily. The study is in two parts. In Part 1 of the study, small groups of patients were treated at increasing doses to find the highest safe dose and best dose to give to patients in Part 2 of the study. 43 patients with advanced solid tumours were treated in Part 1.
In Part 2, the dose found to be safe in Part 1 is given to patients with diffuse large B cell lymphoma and Burkitt's Lymphoma. 15 - 20 patients will be treated in Part 2.
Patients will need to visit the hospital weekly for two months and then every fortnight. Patients will have regular blood and urine tests, scans, heart traces and eye tests amongst other clinical tests. Research blood samples will also be taken to look at what happens to the drug inside the body. Treatment will continue until a patient's cancer starts growing but can continue for up to a maximum of 12 months if the cancer is responding to the drug. It is important to explain that this is the first study of this drug and patients will have advanced cancer so it is unlikely that patients will benefit directly from taking part but the study may help improve future treatment of cancer.
|Condition or disease||Intervention/treatment||Phase|
|Adult Solid Tumor Diffuse Large B Cell Lymphoma Burkitt Lymphoma||Drug: AZD3965||Phase 1|
Part 1 followed a rolling six dose escalation schedule of AZD3965 until the maximum tolerated dose (MTD) was defined.
43 patients with advanced solid tumours were treated in Part 1 of the study. A recommended Phase II dose (RP2D) has been proposed from the safety, pharmacokinetic, and proof of mechanism of lactate transport inhibition in peripheral blood mononuclear cells (PBMCs) results from Part 1.
All patients in Part 2 will be treated at this RP2D to further explore the tolerability of this dose and schedule and to explore proof of principle of MCT1 inhibition in tumour types that were shown to express MCT1 and in which AZD3965 showed some effect pre-clinically (diffuse large B cell lymphoma and Burkitt's Lymphoma).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||63 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Cancer Research United Kingdom Phase I Trial of AZD3965, a Monocarboxylate Transporter 1 Inhibitor (MCT1) in Patients With Advanced Cancer|
|Study Start Date :||February 2013|
|Estimated Primary Completion Date :||December 2019|
|Estimated Study Completion Date :||December 2019|
- Drug: AZD3965
AZD3965 is available as 5, 10, 20 and 30mg capsules and patients took their dose orally once or twice every day of each 28 day cycle including a single dosing day at day-7 prior to Cycle 1 in Part 1 of the study. The RP2D for Part 2 of the study is 10mg BID. Patients can have up to 12 cycles of treatment if patient is benefitting.
- A recommended safe and biologically active dose of AZD3965 for evaluation in Phase II trials. [ Time Frame: 48 Months ]
- Pharmacokinetic profile of AZD3965 in plasma including area under the plasma concentration-time curve (AUC) maximum concentration (Cmax), time to maximum concentration (Tmax) and elimination half-life (T1/2) [ Time Frame: Pre-dose, Day -7, Day1, Day 8 & Day 29 ]
- Changes in the cell death markers M65,M30 and nuclear DNA (nDNA) [ Time Frame: Pre-dose, Day -7, Day1, Day 8 & Day 29 ]
- Objective tumour responses to AZD3965 according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 measured after every 2 cycles [ Time Frame: 48 Months ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01791595
|Contact: Ruth Plummer, Prof||08088004040||Ruth.Plummer@newcastle.ac.uk|
|Royal Marsden Hospital||Active, not recruiting|
|Sutton, London, United Kingdom, SM2 5PT|
|The Beatson West of Scotland, Glasgow||Recruiting|
|Glasgow, United Kingdom|
|Principal Investigator: Pam McKay, Dr|
|Leicester Royal Infirmary||Recruiting|
|Leicester, United Kingdom|
|Principal Investigator: Martin Dyer, Prof.|
|Manchester, United Kingdom|
|Principal Investigator: Kim Linton, Dr|
|Freeman Hospital||Active, not recruiting|
|Newcastle upon Tyne, United Kingdom, NE7 7DN|
|Plymouth, United Kingdom|
|Principal Investigator: Simon Rule, Prof.|