The drug STI-571 will soon enter clinical trials for glioblastoma, a kind of brain tumor, and for gastrointestinal stromal tumors and leukemia under a new agreement between the National Cancer Institute and Novartis Pharmaceuticals, the company that makes STI-571. Initially tested in chronic myelogenous leukemia, the experimental drug has also shown promise for some solid tumors.
Under the agreement (a Letter of Intent for a Cooperative Research and Development Agreement), NCI will sponsor clinical trials to test STI-571 through its networks of researchers and institutions around the country. The North American Brain Tumor Consortium will carry out the glioblastoma trial, an early (phase I/II) study. This trial will investigate the proper dosage of the drug, how it interacts with other medicines used by glioblastoma patients, and whether there is evidence of clinical benefit in these patients. Designated NABTC-9908, the trial has been approved nationally and will begin enrolling patients in the near future as individual Institutional Review Boards review and approve the protocol.
Also approved is a trial testing STI-571 for gastrointestinal stromal tumors or GIST, a rare cancer that affects connective tissue in the digestive system. The GIST trial (S0033) will test two different doses of the drug in approximately 600 patients with metastatic or recurrent disease. Led by the Southwest Oncology Group (SWOG), it will involve a number of other NCI Cooperative Clinical Trials Groups as well.
At present, there is no effective standard treatment for GIST. Positive results with STI-571 in an early, small trial, however, led to a concerted effort to speed the development of the upcoming randomized study. As with the glioblastoma trial, the GIST trial also will open for enrollment around the country as Institutional Review Boards approve it.
In addition, a current trial in Europe (EORTC-62001) is using STI-571 to treat several different types of soft tissue sarcomas, including GIST.
NCI and Novartis plan to collaborate on further study of STI-571 for chronic
myelogenous leukemia (CML). They also plan to study its use in acute
lymphoblastic leukemia (ALL) cases in which cells have the abnormality known
as the Philadelphia chromosome (Ph+ ALL). Several small pilot trials will
pair the drug with chemotherapy in various phases of CML or in Ph+ ALL, and
one trial in chronic phase CML will pair it with interferon-alpha.
On its own, STI-571 has shown promise against CML. For instance, in a study highlighted at the December 2000 meeting of the American Society of Hematology (ASH) in San Francisco, the drug elicited a response in patients who had not responded to interferon-alpha. After six months of STI-571, half of the 500-plus patients had significantly fewer Ph+ bone marrow cells than at the beginning of the study, and about 90 percent achieved normal blood counts. Carried out by researchers including H. Kantarjian, M.D., of M.D. Anderson Cancer Center in Houston, Texas, the trial is one of many STI-571 clinical and laboratory studies that were presented at ASH.
STI-571, which Novartis has named Glivec, is one of the new class of biologic agents known as signal transduction inhibitors. Targeted at specific molecules, these drugs are designed to interfere with biochemical signals that spur the growth of cancer cells.
Current trials with STI-571 are listed in NCI's searchable database for clinical trials, PDQ, as are other trials for CML.
Patients interested in participating in STI-571 trials can also call Novartis at 800-340-6843.