A clinical trial testing a new treatment combination in patients with leukaemia launches through the Combinations Alliance, a joint initiative between Cancer Research UK and the Experimental Cancer Medicine Centres (ECMC) Network, today (Wednesday).
Researchers want to discover whether AstraZeneca and MSD’s experimental medicine, selumetinib (AZD6244, ARRY-142886), can be effective in combination with dexamethasone, a treatment already used for several conditions including leukaemia.
Run by the Cancer Research UK Clinical Trials Unit based at the University of Birmingham*, SeluDex is the first clinical trial to include both adults and children in the Combinations Alliance portfolio. This trial is planned to open in 23 centres throughout the UK and in 11 additional centres spanning 6 European countries, to help recruit an initial 42 patients.
The phase 1 trial will examine both adults and children who have had a relapse of their acute lymphoblastic leukaemia (ALL) or refractory ALL, and who have a mutation in a gene involved in the RAS pathway.** It is the first trial to incorporate such an innovative design enabling both paediatric and adult patients to test this novel combination at the same time.***
Researchers will investigate the most suitable dose of selumetinib in combination with dexamethasone. They will also gather some preliminary information on the effectiveness of the combined treatment.
Dexamethasone belongs to a group of drugs called glucocorticoids. These are important in the treatment of leukaemia because they can stimulate the death of cancer cells. Selumetinib works to inhibit enzymes called MEK 1/2 which are critical components of the so-called RAS-ERK pathway. This pathway is implicated in driving cancer growth and progression.****
Professor Josef Vormoor, international clinical lead for the trial, said: “Although there are effective treatments for leukaemia, for some patients, the disease can return after they have been treated. If this combination is successful, it could give us an urgently needed new way to treat patients who have relapsed and have few treatment options left.”
George Kirk, Global Medicines Leader for selumetinib at AstraZeneca said; “Through our strategic collaboration with MSD on developing selumetinib, we are delighted to continue the long-standing relationship with Cancer Research UK and in particular, to have the opportunity to explore how selumetinib could contribute to the treatment of ALL in this innovative trial.”
Dr Ian Walker, Cancer Research UK’s director of clinical research, said: “It’s hugely exciting to launch the first children’s trial through our Combinations Alliance. We think it’s important to support research into promising new combination therapies and provide more treatment options to both adults and children living with cancer.”
“The Combinations Alliance was established to enable partnerships between drug development companies and researchers to identify new combinations of drugs in the hope of improving treatments and saving more lives from cancer. This is the first time that we have been successful in establishing a novel trial design involving both adults and children and we hope that this treatment combination will help more patients with leukaemia.”
*SeluDex clinical trial is sponsored by the University of Birmingham and managed by the Cancer Research UK Clinical Trials Unit.
**The activation of RAS genes is required for a cell to grow and divide. In healthy cells, the proteins made by RAS genes are switched on by a signalling pathway, but in cancer, the faulty RAS oncogene produces a defective protein that is always switched on. This means the signalling pathway is always active, leading to unchecked cell growth and division.
***Up to 42 patients will be recruited to the trial. One trial arm will recruit adults aged 18 and above and the other will recruit children and teenagers under the age of 18.
****Selumetinib is an oral, potent and highly selective MEK 1/2 inhibitor developed by AstraZeneca and MSD, known as Merck in the US and Canada.
About the ECMC network
The Experimental Cancer Medicine Centres (ECMC) network is an initiative funded by Cancer Research UK in partnership with the four health departments of England, Scotland, Northern Ireland and Wales. Launched in 2007 with a total investment by the funders of over £100million, this infrastructure award supports a network of 18 adult centres (of excellence) and 11 paediatric locations throughout the UK. By bringing together world-class scientific and clinical expertise the ECMC network advances the boundaries of cancer care, with over 3,000 patients recruited onto over 400 ECMC-supported trials in 2016-17. Collaboration with Industry is key to the success of the ECMC – in 2016/17 alone, ECMCs leveraged over £80 million from their commercial partnerships. Find out more at www.ecmcnetwork.org.uk or tweet us at @ECMC_UK
About the Combinations Alliance
The Combinations Alliance is a Cancer Research UK supported academic-industry initiative. The alliance facilitates translation of academic research ideas into early phase combination clinical trials by working alongside both industry and the adult and paediatric researchers in our world class network of Experimental Cancer Medicine Centres (ECMC). The initiative enables research into novel drug combinations, bringing cancer patients more treatment options that otherwise would not be possible.
About the University of Birmingham: CRUK Clinical Trials Unit (CRCTU)
The CRCTU is one of the largest cancer trials units in the UK and has been in existence for more than 30 years. The CRCTU specialise in the design, conduct and analysis of phase 1 to 4 cancer clinical trials for Investigators nationwide and internationally in a number of specialist areas including paediatric, lung, breast, gastrointestinal, gynaecological, urological and hepatobiliary cancer. The CRCTU has experience in trials involving investigational medicinal products, including first in man studies, radiotherapy, devices, surgery, allogenic stem cell transplantation, gene therapy, immunotherapy and biomarkers. For more information please visit: https://www.birmingham.ac.uk/research/activity/mds/trials/crctu/about/index.aspx