Novacea Inc. began a Phase II/III trial of DN-101, its own formulation of calcitriol, which will be studied in combination with Taxotere as a potential treatment for androgen-independent prostate cancer.

Novacea, of South San Francisco, was founded in July 2001 by Domain Associates and has raised $12 million to date, said M.J. Whitehouse, vice president of early development at Novacea.

"It's our first Phase II trial, so I think it represents very rapid progress in the clinic for a company to be in a large Phase II study within 14 months of its initiation," Whitehouse told BioWorld Today.

Eckard Weber, a venture partner at Domain, which is based in Princeton, N.J., and Laguna Niguel, Calif., is a founder and chairman of Novacea.

The ASCENT (AIPC study of calcitriol enhancing taxotere) trial will involve 232 patients who have androgen-independent prostate cancer, an advanced form of prostate cancer. The randomized, double-blind trial will be conducted at about 20 medical centers in the U.S., the company said. Whitehouse said Novacea is collaborating with Aventis SA, of Paris, in the ASCENT trial, which they are jointly funding. Aventis is the maker of Taxotere.

If the current study has positive results, Novacea will go forward with a Phase III trial. The company already is discussing possible endpoints for a Phase III trial with the FDA, she said.

Calcitriol is a naturally occurring hormone and the most potent biologically active form of vitamin D, Novacea said, and DN-101 is the company's formulation specifically designed for cancer.

The Phase II/III trial is being conducted to confirm an earlier, open-label Phase II study of calcitriol with Taxotere, rather than for registration purposes, Whitehouse said.

Novacea said the primary endpoint for the trial is a reduction from baseline of 50 percent or more in prostate-specific antigen in patients, who will receive high-dose pulse administration. The secondary endpoints include tumor response rate in measurable disease, PSA progression-free survival, time to clinical progression and overall survival, the company said.

The company was founded by Domain Associates, but its foundation rests on the scientific findings of Donald "Skip" Trump and Candace Johnson of the Roswell Park Cancer Institute in Buffalo, N.Y., as well as Tomasz Beer, now a member of Novacea's clinical advisory board and an assistant professor of medicine at the Oregon Health & Science University Cancer Institute.

"Dr. Beer had an interesting hypothesis, which was that pulse-dosing, giving [calcitriol] weekly as opposed to daily, would allow the dose to be escalating to the level that it gives an antitumor effect," Whitehouse said.

Novacea's first task was to develop the high-dose formulation of calcitriol, which consists of 80 capsules a week, specifically designed for cancer patients, Whitehouse said. She likened the treatment to chemotherapy, where someone with cancer essentially is poisoned and the body allowed to "recover from the insult."

"What Dr. Beer did was to use that same philosophy in calcitriol," Whitehouse said.

Beer's Phase II study of calcitriol with Taxotere determined that 30 of 37 patients, or 81 percent, treated with high doses of calcitriol and Taxotere had a reduction of 50 percent or more in PSA, which is used to measure the presence and progress of prostate cancer.

Other investors in privately held Novacea include Sofinnova Ventures, of San Francisco, and ProQuest Investments, of Princeton, N.J., and San Diego.