Tactical’s Product, CTO, has improved oral bioavailability, is more effective and less toxic in animal cancer models than Merck’s CAI. CAI, was tested for fifteen years, by scientists at the National Cancer Institute (NCI) and was found to cause serious side effects in cancer patients entered in several Phase II clinical trials. CAI has been discontinued because of this. Some clinical studies of CAI are:
Phase I and Phase II clinical trials of the Merck product for prostate and ovarian cancer have been undertaken by investigators at the National Cancer Institute and the National Institutes of Health. Some stabilization of the disease has been reported with CAI. Clin Cancer Res 2001, 7:1600-1609; Clinical Cancer Res, 1999, 5:2324-2329; Invest New Drugs, 2002, 20:183-194
However, in a Phase II clinical trial of fifteen patients who had D2 androgen-independent prostate cancer and soft tissue metastases. Grade III toxicity was observed and the study had to be discontinued. Clinical Cancer Res, 1999, 5:2324-2329.
Clinical studies have also been carried at other Cancer Centers to improve the bioavailability of Merck’s Product by combining it with ketoconazole in Phase I trial in 47 patients. Ketoconazole inhibits the metabolism of CAI. This study demonstrated that the bioavailability of CAI was improved by ketoconazole, but the toxicity associated with CAI remained unchanged. Cancer Chemotherapy Pharmacol 54: 377-384, 2004, “A phase I trial of pharmacokinetic modulation of carboxyamidotriazole (CAI) with ketoconazole in patients with advanced cancer”.
Tactical expects the structural change in CTO to reduce neurotoxicity and optic toxicity observed in humans with CAI based on preclinical toxicokinetic studies in rats and dogs.
