Last updated on April 2016

A Phase I Trial of AZD3965 in Patients With Advanced Cancer


Brief description of study

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, small groups of patients will be treated at increasing doses to find the highest safe dose and best dose to give to patients in Part 2 of the study. Approximately 18 patients with advanced solid tumours or lymphomas will be treated in this part. In Part 2, the dose found to be safe in Part 1 will be given to three groups of patients with either prostate cancer, gastric cancer or diffuse large B cell lymphoma. 15 patients will be treated in each group. 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.

Detailed Study Description

Part 1 will follow a rolling six dose escalation schedule of AZD3965 until a tolerated dose at which MCT1 is inhibited (as measured by at least a four-fold change relative to baseline in peak lactate levels in PBMCs) and/or the maximum tolerated dose (MTD) is defined. Approximately 36 patients with advanced solid tumours or lymphoma will be entered into Part 1. The final number will depend on the number of dose escalations required to reach MTD or the tolerated dose at which MCT1 is inhibited. A recommended Phase II dose (RP2D) will be 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 (prostate) or in which AZD3965 showed some effect pre-clinically (gastric and diffuse large B cell lymphoma).

Clinical Study Identifier: NCT01791595

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Udai Banerji, Dr

Royal Marsden Hospital
Sutton, United Kingdom
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Elizabeth R Plummer

Freeman Hospital
Newcastle upon Tyne, United Kingdom
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