Phase I Clinical Data on Novel Anticancer, Antiangiogenesis Drug

Data from a phase I clinical trial of CT-2584, a novel small-molecule, anticancer, antiangiogenesis drug under investigation for the treatment of chemotherapy-resistant (advanced and refractory) cancers were presented at the 34th Annual Meeting of the American Society of Clinical Oncology in Los Angeles.

The data were reported by Roger Waltzman, MD, lead author. David Spriggs, MD, is the senior author and principal investigator for the trial, which is being conducted at the Memorial Sloan-Kettering Cancer Center in New York City. The study is designed to establish a maximum tolerated dose of CT-2584, develop a pharmacokinetic profile of the drug, and evaluate its antitumor effects. This study is a companion to one being conducted at Christie Hospital in Manchester, England.

Preliminary Results

In this study, CT-2584 is administered intravenously over 6-hour infusions for 3 consecutive days, followed by 18 days during which no CT-2584 is administered. This constitutes one cycle of therapy. If no dose-limiting toxicities are observed during the first cycle, a second cycle of therapy is administered. Patients who have received two cycles are evaluable for antitumor response. Patients whose cancers have become stable or have decreased in size are eligible to receive up to a total of six cycles of CT-2584 therapy.

In the United States, 23 patients have been enrolled in the trial, 22 at Memorial Sloan-Kettering and one under a compassionate study using the Memorial Sloan-Kettering protocol described above. All 23 patients are evaluable for toxicities, with 18 evaluable for tumor response.

To date, no dose-limiting side effects, such as severe nausea and vomiting, low blood counts, or gastrointestinal damage, have been observed. Of the 18 patients evaluable for tumor response, 13 remain alive at a median of 8 months (range, 2 to 19 months) after treatment with CT-2584. Five patients (27%) have experienced tumor stabilization.

Carolyn Paradise, md, head of medical affairs at Cell Therapeutics, producers of the drug, stated: "We continue to be impressed with the activity of CT-2584 seen in these early trials and by the tolerability profile of the drug. Combined with patients enrolled in our CT-2584 trial in the United Kingdom, we have treated more than 50 patients, 35 of whom were evaluable for tumor response to CT-2584. It is exciting that 10 (29%) of these patients’ cancers stabilized on CT-2584, and that 7 are still alive after a median of 10 months following treatment. Overall survival for all 35 evaluable patients in both trials is also very encouraging with 21 alive a median of 10 months after starting treatment with CT-2584. With this tolerability profile, synergistic effects with certain standard chemotherapeutics, and the possibility of oral administration, chronic longer-term outpatient therapy may be possible. This could be a major benefit for cancer patients."

Drug Shows Particular Promise in Advanced Prostate Cancer and Sarcomas

According the James A. Bianco, MD, president and CEO of Cell Therapeutics, CT-2584 appears to be particularly promising in the treatment of patients with advanced prostate cancer and sarcomas. "We believe this to be attributable both to the direct tumor toxic effects of CT-2584 and to its potent antiangiogenic effects," said Dr. Bianco. "Based on the results observed thus far, we plan to begin phase II trials this year in both advanced prostate cancer and in advanced sarcomas.

It is believed that CT-2584 has a unique mechanism of action of tumor-cell killing. This mechanism involves CT-2584’s effect on tumor-cell phospholipids, such as phosphatidic acid, which are believed to play an active role in neoplastic cell transformation. In preclinical studies, CT-2584 was effective in vitro against a broad array of tumor cell types, including those resistant to multiple kinds of chemotherapy drugs at drug levels that were nontoxic to normal human bone marrow cells. In addition, CT-2584 significantly inhibited cancer cell-induced angiogenesis at drug levels below which cancer-cell killing was observed.