|
By Suzie Siegel
LMS patients can participate in one of the largest clinical trials ever attempted for people with sarcoma.
The Sarcoma Multi-Center Clinical Evaluation of the Efficacy of Deforolimus (SUCCEED) started in September. ARIAD Pharmaceuticals has partnered with Merck & Co. to develop deforolimus worldwide. They hope to have 50 sites in the United States before April, said Dr. Camille Bedrosian, chief medical officer of ARIAD.
She said deforolimus, the first oral mTOR inhibitor, has "exquisite specificity for mTOR," a protein that serves as a "master switch" in cancer cells. Blocking mTOR can starve cancer and keep it from growing. Eventually, she said, deforolimus may be combined with other targeted therapies as well as cytotoxic agents (the more common chemotherapy).
Dr. Bedrosian discussed the phase III trial at the International Sarcoma Patient Advocate Network (iSPAN) meeting Oct. 31, 2007, in Seattle, as well as at a dinner afterward with advocates. She and her colleagues also answered questions during the meeting Nov. 1-3 of the Connective Tissue Oncology Society (CTOS).
Dr. Gina D'Amato presented a paper on deforolimus at the CTOS conference. It was co-authored by other prominent medical oncologists who study sarcoma. To read an abstract, as well as more about the conference, go to:
http://www.ctos.org/meeting/2007/07mtgProgram.pdf
In a phase II trial, deforolimus (also known as AP23573) was tested on 212 people with bone and soft-tissue sarcoma, including LMS. Most had been "heavily pre-treated" with chemo, and their cancers were growing, said Dr. D'Amato, formerly of the Moffitt Cancer Center in Tampa and now with Winship Cancer Institute in Atlanta.
A third of the patients got some benefit from deforolimus, she said, and patients who responded to the drug lived twice as long as patients who didn’t respond.
Dr. Bedrosian predicts deforolimus will work best for patients with faster-growing sarcoma. ARIAD will follow trial participants for up to five years, she said. She said it gets records from physicians; it doesn’t contact patients.
Some patients saw rapid growth in their LMS after leaving the phase II trial. Dr. Bedrosian said deforolimus functions like Herceptin and Gleevec in the sense that it suppresses tumor growth. Once that suppression is removed, tumors may grow again.
For the phase III trial, ARIAD hopes most people who want to participate will find a site near them, Dr. Bedrosian said. It has no provision for paying travel or lodging costs, she said, but might consider doing so on an individual basis if a prospective patient lived far from any site.
People must be age 13 or older to enroll. They must have had at least four cycles of chemo, with an "ongoing favorable response." That could be remission, shrinkage or stability. The hope is that deforolimus can maintain that status as long as possible.
Why would someone who has had a favorable response to chemo want to take deforolimus? People who have gotten remission are unlikely to stay on chemo, but they may want to take deforolimus in hopes of staving off a recurrence. Also, it is common for people on chemo to take a break from time to time to let their body recover a bit. Those who have had shrinkage or stability may want to take deforolimus while on a break from chemo. Others may have reached their limit of a certain kind of chemo or be waiting to figure out what to do next.
Participants can't do other treatments at the same time as the deforolimus trial. That would make it harder to gauge the effectiveness of the deforolimus, Dr. Bedrosian said.
People will be chosen at random to receive either deforolimus or a placebo. Patients don't like the idea that they might get a placebo, but doctors noted that this trial doesn't involve patients with advancing disease. Even so, why test the drug against a placebo?
"How are we going to know if it works?" Dr. Bedrosian said. Dr. Sant Chawla of Los Angeles added, "Someone has to prove this to the nonbelievers. Otherwise, we’ll be talking about this for 10 years."
If people get new tumors or their existing tumors grow, they have to leave the trial. Those who were on the placebo can't get the drug, Dr. Bedrosian said, because that would affect the trial results. People who complete the trial will be told whether they got the drug or the placebo. If they got the placebo, they will not be allowed to get the drug.
If people get side effects, won't they know they are getting the drug, not the placebo? For example, she said, about 70 percent of the people who took deforolimus before have gotten mouth sores.
But some of these sores were minor – similar to what people get in the general population, she said. People who have had chemo recently may have a hard time distinguishing chemo side effects from the side effects of deforolimus.
ARIAD doesn't have a compassionate-use program, but will consider it, she said. This would entail giving the drug to people who don't qualify for the trial but have few other options.
Although "overall survival" is the goal, ARIAD has gotten FDA permission to use "progression-free survival" as its endpoint for judging the effectiveness of deforolimus.
"It’s very difficult to get FDA approval with an endpoint of progression-free survival," Dr. Bedrosian said. "The fact that ARIAD got to do this is phenomenal."
The FDA has approved very few drugs to treat sarcoma. Some doctors are reluctant to try a drug that has been approved for a different kind of cancer, and some insurance companies and government programs won't pay for these drugs. An example is Medicare's refusal to pay for Gemzar + Taxotere for LMS patients in some states.
For more information, go to:
http://phx.corporate-ir.net/phoenix.zhtml?c=118422&p=irol-newsArticle&ID=1054494&highlight
People interested in participating in the deforolimus trial can call 1-877-621-2302 or go to www.succeedtrial.com.
|
