Phase II Double-blind Placebo-controlled Trial of CY503 in Patients With Chemotherapy-refractory Metastatic Colorectal Cancer

Colorectal cancer has a worldwide annual incidence of approximately 1 million new cases diagnosed yearly and it is the second leading cause of cancer-related death in Western nations. There are a couple of approved standard therapies for the treatment of MCRC with cytotoxic agents irinotecan, oxaliplatin, and the fluoropyrimidines , as well as bevacizumab, the antibody against vascular endothelial growth factor A, and cetuximab, the antibody against the epidermal growth factor receptor. But there are only a few studies achieving a median survival time of more than 20 months in MCRC patients with standard regimens. After a 1st line therapy a high proportion (50% to 80%) of patients receives a 2nd line therapy with drugs not used in 1st line therapy and a part of them gets a 3rd line treatment. Results from a 2nd line therapy are best response rates ranging from 4 % - 23 %, a median PFS rate of 5.1 months, a median TTP of 4.1 - 4.6 months and median overall survival 6.9 - 12 months. However, for patients who experience disease progression after standard therapy (definition see inclusion criteria) there is no further standard therapeutic option. These patients developed a resistance to these therapies and finally die of their disease. They generally get best supportive care (BSC). Thus, there is a need for new active treatment options in this setting.

In this phase II double-blind placebo-controlled trial the efficacy and safety of CY-503, 350 ng s.c. injected in patients with chemotherapy refractory MCRC are tested. Approved treatments given to MCRC patients are usually discontinued after a treatment over some weeks at the first detection of objective PD. It will be tested if CY-503 is able to achieve progression-free-survival (PFS) in comparison to placebo. Patients will initially be included to receive either CY-503 or placebo until documentation of objective PD.

Standard therapy must be finished and has shown objective PD. Also patients with contraindications to standard therapy can be included.

CY-503 shows the potential to improve treatment of MCRC. This study aims at evaluating the activity and therapeutic effects of the substance. Anticipated capabilities are substitution of cytostatic drugs or improvement of their efficacy and tolerability . Furthermore, the expected improvement of PFS rates after failure of standard chemotherapies has to be investigated.

In a phase I trial CY-503 showed SD in patients who had exhausted standard therapy options for metastatic disease with subsequent disease progression with a median TTP of 17.4 weeks.