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IPI-504 (Retaspimycin)
IPI-504 (generic name retaspimycin) is under development by manufacturer Infinity Pharmaceuticals in conjunction with MedImmune, a part of AstraZeneca. This drug targets Heat-shock protein 90 (Hsp90). Hsp90 is one of a class of chaperone proteins, whose normal job is to help other proteins acquire and maintain the shape required for those proteins to do their jobs. Chaperone proteins work by being in physical contact with other proteins. Hsp90 can also enable cancer cells to survive and even thrive despite genetic defects which would normally cause such cells to die. Thus, blocking the function of Hsp90 and related chaperone proteins may cause cancer cells to die, especially if blocking chaperone function is combined with other strategies to block cancer cell survival.
New RING Trial
Infinity, in collaboration with its partner MedImmune (a unit of AstraZeneca), has launched a registration trial of IPI-504 in refractory GIST. This trial is listed as NCT00688766 and is now open. The trial is known as the RING trial (Retaspimycin hydrochloride IN GIST). A dedicated website describing the trial, locations as they open, and details is available at http://www.ringtrial.com/
In this trial, patients will be randomized to receive either IPI-504 (retaspimycin hydrochloride) or placebo intravenously two times a week for two consecutive weeks, followed by a week of rest. This three-week period is called a cycle. Patients are required to visit the clinic to receive an infusion twice a week during each treatment week of the cycle.
The length of time a patient participates in the trial will depend on how long a patient responds to treatment. CT scans or MRIs will be performed early and often in the clinical trial to best evaluate a patient’s response to IPI-504 or placebo. Patients will receive scans on weeks 2, 5, and 8 for the first 8 weeks of the study and then every 6 weeks thereafter. If it is determined that a patient’s cancer has grown and the patient has been receiving placebo, the patient will have an opportunity to switch to treatment with IPI-504.
This is a list of currently open trial sites. Additional trial sites will be opened on an ongoing basis. Please visit this site regularly for updates. Eventually there will be numerous locations in the USA and in Europe.
California
Site: Ceders Sinai Medical Center
Physician: Dr. Charles Forscher
Contact: Ginny Naessig
Phone: 310-423-0721
Email: vnaessig@csocc.com
Site: City Of Hope
Physician: Dr. Warren Chow
Phone: 626-256-HOPE (4673)
Massachusetts
Site: Dana Farber Cancer Institute
Physician: Dr. George Demetri
Contact: Tarsha Colon, RN
Phone: 617-632-5117
Email: tcolon@partners.org
Site: Massachusetts General Hospital
Physician: Dr. Edwin Choy
Phone: 877-789-6100
Illinois
Site: Oncology Specialists S.C.
Physician: Dr. Pamela Kaiser
Phone: 866-611-1991
North Carolina
Site: New Bern Cancer Center
Physician: Dr. Rick Gorman Jr.
Contact: Jenifer Haggard
Phone: 252-638-0422
Email: jenifer.haggard@quintiles.com
Pennsylvania
Site: Fox Chase Cancer Center
Physician: Dr. Margaret Von Mehren
Contact: New Patient Office
Phone: 1-888-FoxChase
Results from the Phase I trial
IPI-504 entered a Phase I trial for GIST patients in January 2006, which has been completed and is closed. As of January 2008, an expansion of the Phase I trial was fully accrued.
Data about IPI-504 trial performance were presented at the June 2008 ASCO meeting: you can link to this abstract by clicking the title below:
Inhibition of heat shock protein 90 (Hsp90) with the novel agent IPI-504 in metastatic GIST following failure of tyrosine kinase inhibitors (TKIs) or other sarcomas: Clinical results from phase I trial. Abstract - No. 10503
Here is a link to more IPI-504 information from the manufacturer.
To download a pdf of a poster presented at EORTC 2006 about early results with IPI-504, click the preceding word "poster" and then use the magnification feature of Adobe reader to enlarge the poster for easy reading (try viewing at 200% manification). This poster was graciously provided by Infinity Pharmaceuticals.
A January 2007 presentation about IPI-504 at the ASCO Gastrointestinal Cancers Symposium is available at this link. You can choose to view the slides only or the webcast (voice of speaker plus slides) by selecting either the "slides" or "video" icon under #2 below the abstract.
A scientific paper about IPI-504 published electronically in November 2006 is available free-access through the journal Proceedings of the National Academy of Sciences at this link. The paper, by Sydor et al, is entitled "Development of 17-allylamino-17-demethoxygeldanamycin hydroquinone hydrochloride (IPI-504), an anti-cancer agent directed against Hsp90."
Here is a link to a very detailed scientific article in Medscape about
Here is a link to information about Hsp90 in Wikipedia.
http://www.gistsupport.org/treatments/emerging-treatments/hsp90-inhibitors/ipi504-retaspimycin.php
