ASTFOX
Research type
Research Study
Full title
ASTFOX : A Phase I study of IAP antagonist, ASTX660 (tolinapant), in combination with standard of care FOLFOX chemotherapy in metastatic colorectal cancer
IRAS ID
1004428
Contact name
Victoria Coyle
Contact email
Sponsor organisation
Greater Glasgow Health Board
Eudract number
2021-006411-28
ISRCTN Number
ISRCTN11197711
Research summary
In this study, its investigating whether a new drug called ASTX660 can be combined with FOLFOX chemotherapy, a combination of two chemotherapy drugs (oxaliplatin and 5-fluorouracil) routinely used in treatment of advanced bowel cancer. ASTX660 is an “IAP antagonist”, in other words, it combats IAPs. IAPs (Inhibitors of apoptosis proteins) are proteins that can block cells from dying by a process called apoptosis. This cell death helps to maintain the balance of cells in the body and is used to remove cells that are old or damaged. When cancer cells are damaged by chemotherapy they can die by this process, however some cancer cells have the ability to avoid apoptosis and can survive despite chemotherapy treatment. Therefore stopping the IAPs from blocking apoptosis could increase the likelihood of damaged cancer cells dying. We have shown this in laboratory tests in bowel cancer cells. It's also been shown this type of drug causes changes in the types of cells and chemical signals in the tumour and surrounding tissue which could trigger cell death by activating the patient’s immune system. ASTX660 is a new drug that's not licensed for treatment of cancer. It has been tested on its own in clinical trials and has shown to be safe and well tolerated by patients with a range of cancer types but has not been tested in combination with FOLFOX chemotherapy. The purpose of this study is to find the dose of ASTX660 that can be given with FOLFOX chemotherapy, without producing side effects that are serious or detrimental to patients’ day-to-day life. At least three patients at a time will receive treatment, with stepwise increases in the dose of ASTX660, provided the side effects seen in treated patients are acceptable. The dose of ASTX660 with the most acceptable side effect profile will be recommended as the dose to be given in combination with FOLFOX chemotherapy for further studies. Up to 30 patients will be treated in the study from 3 hospital sites in the UK.
REC name
Wales REC 1
REC reference
23/WA/0173
Date of REC Opinion
5 Sep 2023
REC opinion
Further Information Favourable Opinion