Millennium Pharmaceuticals Inc announced the recent initiation of a phase II clinical trial of Velcade in patients with colorectal cancer. The randomized, open-label study will assess the response rates of patients with refractory metastatic colorectal cancer to treatment with Velcade alone or Velcade plus Camptosar (irinotecan hydrochloride injection). Velcade is currently in a phase III study in patients with multiple myeloma and a range of phase I and II clinical trials in patients with hematologic and solid tumors.

We have seen encouraging preclinical and early clinical results with bortezomib in solid tumors that have provided the scientific basis to initiate this phase II study," said principal study investigator David P. Ryan, from Massachusetts General Hospital. These preliminary results have shown that the combination of bortezomib plus irinotecan at full doses was well tolerated and did not appear to exacerbate the most problematic side effects commonly seen with this standard chemotherapy agent.

Velcade is designed to specifically block proteasomes, which are enzyme complexes in the cell responsible for breaking down a variety of proteins, including many that regulate cell division. In preclinical studies, inhibition of the proteasome has shown to lead to the disruption of cell cycle progression, resulting in cancer cell death (apoptosis). Velcade is the first and only proteasome inhibitor currently in clinical trials for treating cancer.

The clinical trial is being conducted at approximately 20 sites in North America in up to 175 patients with colorectal cancer whose disease has progressed following treatment with no more than two prior chemotherapeutic regimens. Up to 75 patients will be randomized to a treatment arm of Velcade (bortezomib) for Injection alone and up to 100 patients to a combination arm consisting of Velcade and Camptosar. The primary endpoint of the study is tumor response.

The initiation of this phase II trial represents not only an important milestone in the development of Velcade, but further emphasizes our commitment to growing the Millennium oncology franchise, said Barry Greene, general manager, oncology franchise at Millennium. The early data we have seen from our various phase I combination trials hold promise for the further expansion of our solid tumor program and we are continuing to aggressively pursue the development of Velcade in solid tumors.