Cancer Research UK (CRUK) in conjunction with Astex Pharmaceuticals has begun a Phase I/II Trial to measure the success of a DNA methyltransferase (DNMT) inhibitor that can halt the progress of bladder cancer proving resistant to chemotherapy. During the trial, Astex Pharmaceuticals DNMT Inhibitor (AKA guadecitabine – SGI-110) is to be administered along with chemotherapy.
In the Phase I trial, CRUK shall administer the DNMT Inhibitor guadecitabine to patients with advanced “solid tumors” in low dosages to determine overall safety and confirmation of correct dosage. With baselines established during Phase I study, Phase II will entail bladder cancer patients who prior to surgery will be required to undergo three to four cycles of chemotherapy. A group of these patients will get both the aforementioned chemotherapy in conjunction with the DNMT Inhibitor guadecitabine, while others will receive chemotherapy alone.
This course of action is prompted by understanding the mechanism concerning the DNMT Inhibitor guadecitabine, and the development of resistance to chemotherapy. DNMT allows for epigenetic modifications directly linked to the development of resistance to chemotherapy. The hope is that the DNMT Inhibitor guadecitabine will halt those epigenetic modifications and allow the chemotherapy to be successful.
This trial is being conducted by CRUK under the “Combinations Alliance” which brings CRUK (a non-profit) together with the UK’s “Experimental Cancer Centers Network” in conjunction with for-profit drug developers. The goal being the determination of viable tandem treatments (treatments that are complementary and work well together).
This trial involves the for-profit partner Astex Pharmaceuticals, a biotech company located in the UK and US. Astex Pharmaceuticals has been making steady advances with guadecitabine, and in April to partnered with Genentech to participate in a PD-L1 combination study specific to acute myeloid leukemia. Astex Pharmaceuticals has also explored potential usage on “solid tumors” such as in the CRUK study as well as studies involving melanoma and colorectal cancers.