Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Early clinical trial results back new drug for melanoma

16.04.2008
Rutgers University and the Cancer Institute of New Jersey collaborate in clinical trial

Rutgers Professor Suzie Chen has found that riluzole, a U.S. Food and Drug Administration (FDA) approved drug used to treat Lou Gehrig’s disease (ALS), slows the growth of melanoma, the most aggressive form of malignant skin cancer.

A Phase 0 (zero) clinical trial of riluzole (brand name Rilutek), conducted by James Goydos, a surgical oncologist with The Cancer Institute of New Jersey (CINJ), is in process with a small group of late-stage (stage 3 or 4) melanoma patients. Phase 0 is a recent designation by the FDA for exploratory, first-in-human trials. Goydos reported preliminary but encouraging findings from the trial during a plenary session today at the annual meeting of the American Association for Cancer Research in San Diego.

In about 70 percent of melanoma cases, the disease appears in places that are exposed to the sun. It can then spread to other parts of the body and may become lethal. This type of cancer is not generally responsive to chemotherapy. According to a report from the National Cancer Institute, the incidence rate of melanoma has more than doubled in the past 20 years in the United States.

... more about:
»Clinical »Goydos »Stage »glutamate »melanoma »riluzole »trial

Chen had reported in 2003 the discovery of a gene – Grm1 – responsible for melanoma in laboratory mice. Its normal functions are in the brain, where it is associated with learning and memory; but when this gene is expressed or turned on in certain skin cells, it leads to the development of melanoma.

A common feature to both ALS and melanoma cells is excess glutamate, a cellular growth factor or food for cells. An excess of this protein can overstimulate neurons to the point where they burn out – a possible explanation of what happens in ALS.

In a melanoma cell, the glutamate enters a pernicious loop where it binds to the malfunctioning cell surface protein. The protein operates as a receptor, stimulating the cell to produce more glutamate that, in turn, binds to the receptor, stimulating more production. This cellular “overfeeding” results in the growth and expansion of the melanoma.

“We fixed on riluzole because it is a known inhibitor of glutamate release, the suspected culprit in ALS and possibly melanoma,” said Chen, a professor of chemical biology at the Susan Lehman Cullen Laboratory of Cancer Research in the Ernest Mario School of Pharmacy of Rutgers, The State University of New Jersey, and a CINJ member. “While most of our studies five years ago were with animals, it is humans that we are really interested in.”

In new laboratory experiments using cultures of human melanoma cell lines, riluzole appeared to shut off the glutamate, thus slowing the growth rate of the melanoma cells. Moving forward with animal studies, riluzole demonstrated the same suppression of tumor cell growth and progression seen in cultured cells.

Building on this foundation, Chen joined Goydos to pursue human clinical trials. Goydos is a surgical oncologist and director of the Melanoma and Soft Tissue Oncology Unit at the Cancer Institute of New Jersey, part of the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School (UMDNJ-RWJMS). Goydos is also an Associate Professor of surgery at UMDNJ-RWJMS.

A grant from the National Cancer Institute enabled Goydos to begin an initial or Phase 0 trial. The use of late-stage patients is a requirement. It is a purely experimental exercise designed to make sure the drug that appeared to work in pre-clinical trials is actually performing as expected in humans – “to see if you are hitting your targets,” as Goydos phrased it.

Goydos and his colleagues recruited 11 patients to whom riluzole was administered for two weeks. The researchers tracked the patients’ progress before and after the treatment with biopsies and PET scans, a form of nuclear medicine imaging typically used to detect cancer. “Our preliminary results show three solid positive responses in nine of the patients who had been able to complete the trial to date,” Goydos said. “It is actually quite amazing that we got as many as we did.”

Goydos also noted that there were other patients in the group who showed some indications of responding to riluzole and they will be reassessed when the trial is completed.

“In this situation we hit our target in at least in three, possibly four or five patients,” Goydos said. “It provides enough data to show that we should go on to a more extensive trial.”

The next step is a combined Phase 1/2 trial. Phase 1 will be a toxicity trial where the dosage is increased gradually to determine the appropriate dose and identify possible toxic side-effects.

“We will administer riluzole to the first five or six patients, look for toxicity and then move on to Phase 2,” Goydos said. “We can do this in one combined trial since we are dealing with an FDA-approved drug and not an experimental drug that has never been given to people before.”

Goydos said that the Phase 1/2 trial should begin in August, and he anticipates that it will include between 50 and 100 patients with stage 4 melanoma.

“I think this drug is going to be extremely important as an adjunct to surgical treatment of stage 3 or stage 4 melanoma,” Goydos said. “The challenge is to keep it from recurring, which has happened in patients on the order of 50 percent. With low toxicity likely, riluzole could potentially be given for long periods of time to slow down the metabolic processes responsible for the disease’s recurrence.”

Joseph Blumberg | EurekAlert!
Further information:
http://www.rutgers.edu

Further reports about: Clinical Goydos Stage glutamate melanoma riluzole trial

More articles from Life Sciences:

nachricht Russian scientists show changes in the erythrocyte nanostructure under stress
22.02.2019 | Lobachevsky University

nachricht How the intestinal fungus Candida albicans shapes our immune system
22.02.2019 | Exzellenzcluster Präzisionsmedizin für chronische Entzündungserkrankungen

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: (Re)solving the jet/cocoon riddle of a gravitational wave event

An international research team including astronomers from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has combined radio telescopes from five continents to prove the existence of a narrow stream of material, a so-called jet, emerging from the only gravitational wave event involving two neutron stars observed so far. With its high sensitivity and excellent performance, the 100-m radio telescope in Effelsberg played an important role in the observations.

In August 2017, two neutron stars were observed colliding, producing gravitational waves that were detected by the American LIGO and European Virgo detectors....

Im Focus: Light from a roll – hybrid OLED creates innovative and functional luminous surfaces

Up to now, OLEDs have been used exclusively as a novel lighting technology for use in luminaires and lamps. However, flexible organic technology can offer much more: as an active lighting surface, it can be combined with a wide variety of materials, not just to modify but to revolutionize the functionality and design of countless existing products. To exemplify this, the Fraunhofer FEP together with the company EMDE development of light GmbH will be presenting hybrid flexible OLEDs integrated into textile designs within the EU-funded project PI-SCALE for the first time at LOPEC (March 19-21, 2019 in Munich, Germany) as examples of some of the many possible applications.

The Fraunhofer FEP, a provider of research and development services in the field of organic electronics, has long been involved in the development of...

Im Focus: Regensburg physicists watch electron transfer in a single molecule

For the first time, an international team of scientists based in Regensburg, Germany, has recorded the orbitals of single molecules in different charge states in a novel type of microscopy. The research findings are published under the title “Mapping orbital changes upon electron transfer with tunneling microscopy on insulators” in the prestigious journal “Nature”.

The building blocks of matter surrounding us are atoms and molecules. The properties of that matter, however, are often not set by these building blocks...

Im Focus: University of Konstanz gains new insights into the recent development of the human immune system

Scientists at the University of Konstanz identify fierce competition between the human immune system and bacterial pathogens

Cell biologists from the University of Konstanz shed light on a recent evolutionary process in the human immune system and publish their findings in the...

Im Focus: Transformation through Light

Laser physicists have taken snapshots of carbon molecules C₆₀ showing how they transform in intense infrared light

When carbon molecules C₆₀ are exposed to an intense infrared light, they change their ball-like structure to a more elongated version. This has now been...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Global Legal Hackathon at HAW Hamburg

11.02.2019 | Event News

The world of quantum chemistry meets in Heidelberg

30.01.2019 | Event News

Our digital society in 2040

16.01.2019 | Event News

 
Latest News

JILA researchers make coldest quantum gas of molecules

22.02.2019 | Physics and Astronomy

Understanding high efficiency of deep ultraviolet LEDs

22.02.2019 | Materials Sciences

Russian scientists show changes in the erythrocyte nanostructure under stress

22.02.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>