The National Cancer Institute has expanded an ongoing Phase I clinical trial of a therapeutic vaccine targeting the brachyury protein to include up to 10 patients with chordoma, a cancer that is defined by expression of brachyury.

About the Trial

Researchers at the National Cancer Institute (NCI) are conducting a Phase 1 clinical trial of a therapeutic vaccine, GI-6301, in patients with cancers known to express a protein called brachyury. Brachyury is sometimes over-expressed in a variety of important tumor types including breast, colon, lung, prostate cancers, and others, but is not generally found in normal tissues. Additionally and importantly, brachyury is also present in nearly 100% of chordomas and it has become a defining marker for the disease. The GI-6301 vaccine is intended to stimulate the immune system to fight cancer cells that express the brachyury protein.

The NCI Phase 1 trial of GI-6301, led by Dr. James Gulley, has completed the dose-escalation portion of the trial and has reached the maximum planned dose without any serious adverse reactions. Now the NCI is beginning to enroll a group of 10 patients at the highest dose. Originally, the trial was designed to enroll only patients with metastatic or unresectable locally recurrent cancers, not including chordoma. However, because chordomas nearly always express brachyury, the clinical protocol was recently modified to allow any patient with recurrent chordoma to be enrolled in the trial. This phase of the trial aims to (i) continue to assess the safety of the vaccine, (ii) test whether it causes an immune response to the brachyury protein, and (iii) to assess signs of clinical benefit.

The trial is taking place at the National Institutes of Health clinical center in Bethesda, MD. It involves injections of the vaccine every other week over the course of 7 visits, and then monthly until disease progression. The NCI will pay for transportation costs (including airfare) and a portion of lodging costs for patients enrolled in this study.  If you are interested in learning more about possibly enrolling in this study, please contact Christopher Heery, M.D. at heerycr@mail.nih.gov.

About the Treatment

GI-6301 is a therapeutic vaccine being developed through a Collaborative Research and Development Agreement between the National Cancer Institute and the biopharmaceutical company, GlobeImmune. Designed to stimulate the human immune system to fight cancer, GI-6301 is composed of heat-inactivated S. cerevisiae yeast that expresses human brachyury protein. This product candidate is the fifth of a novel class of yeast-based immunotherapeutics designed to stimulate immune responses to eliminate diseased cells.  Spanning cancer and infectious diseases, these products have been evaluated in ten different Phase 1 and Phase 2 clinical trials.  They have shown a good tolerability profile in clinical programs to date.  Over 400 subjects have been treated thus far, including some who have received monthly dosing for over four years.  Expected adverse events from these products are limited to redness, swelling and tenderness at the injection site, and mild, brief flu-like symptoms.

For eligibility criteria and more information about this trial visit http://clinicaltrials.gov/ct2/show/NCT01519817

Following the Fourth International Chordoma Research Workshop, letters of intent poured in with new ideas and potential collaborations that researchers hope to pursue with a $50,000 seed grant from the Chordoma Foundation. These grants are intended to help researchers start projects, test hunches, and generate preliminary data that could leverage additional funding and lead to sustained chordoma research programs.

By the April 15^th deadline, 45 researchers indicated their intention to submit a grant application - more than double that of the Foundation’s last seed grant review cycle. This large increase in applications reflects the growing number of researchers drawn to study chordoma by the promising opportunities created by recent discoveries.

Applications are due June 3^rd and will be evaluated by a peer-review committee. Funding decisions will be made at the Foundation’s August 12^th board meeting based on the recommendations from the review committee and the availability of funding. Dozens of talented researchers have risen to the challenge of searching for treatments for this once-neglected cancer and the Chordoma Foundation is determined to provide the funding needed to make their work possible. Please help meet the needs of these dedicated researchers by making a donation today!

Last month, doctors, scientists, patients and family members from around the world gathered in Boston for the Fourth International Chordoma Research Workshop and Community Conference.

Highlights from the Research Workshop

• More than 100 participants from nine countries participated, a 30% increase from 2011
• 28 presentations and 18 posters on new, unpublished data
• Six pharmaceutical and biotech companies in attendance, reflecting a growing sense of opportunity to translate discoveries into new therapies for this orphan disease
• Three new clinical trials are planned that will soon open to chordoma patients
• Several drugs were found to stabilize or shrink chordoma tumors in mice
• New chordoma cell lines, mouse models and zebrafish models are being developed, which will enable more compounds to be tested
• The first clinical practice guidelines for chordoma were presented, accomplishing a goal identified at the first research workshop
• Plans were discussed for developing an international patient registry to track patient outcome and quality of life over time and more accurately determine the benefits of various therapies

Photos | Agenda | Presentations | Speaker Abstracts

Highlights from Community Conference

• More than 70 patients, family members and friends from as far away as Romania participated
• Participant questions were answered by six expert physicians
• Research updates were presented by leading chordoma scientists
• Sessions were offered on nutrition and cancer, patient navigation, parenting with chordoma, scanxiety, the skill of happiness and more

Photos | Agenda | Presentations | Speaker Bios

Thank You to Our Sponsors

The Chordoma Foundation is deeply grateful to the individuals, organizations and companies whose support made the Research Workshop and Community Conference possible.

Research Workshop Sponsors

Gold Sponsor
NIH Office of Rare Diseases Research

Silver Sponsors
National Cancer Institute
National Institute of Neurological Disorders and Stroke
UPMC Center for Cranial Base Surgery

Bronze Sponsors
Burroughs Wellcome Fund
MGH Cancer Center
MGH Department of Orthopaedics
MGH Department of Pathology
MGH Harris Center for Chordoma Care
NCI Division of Cancer Epidemiology and Genetics
Sanofi

Community Conference Sponsors

Gold Sponsor
Genentech

Individual Sponsors
Joel and Shari Beckman
Heather Lee and Steve Straus
Jeffrey Nadaner
Karen and Gary Sain
Michael Torrey

Whether a patient, family member, volunteer, donor, physician, or researcher, our connection to chordoma makes us uncommon in what we make of that connection to chordoma; uncommon, as in exceptional, special, or remarkable. At this year’s Community Conference we presented the Foundation’s first annual Uncommon Awards recognizing the contributions of a few supporters.

Dr. Tom DeLaney of Massachusetts General Hospital is leading a new Phase II study that will utilize the newest technology in radiation therapy to treat chordomas.

The study, Phase II Study of High-dose Beam Scanning Proton Radiation Treatment +/- Surgical Resection of Sarcomas of the Spine, Sacrum, and Base of Skull, will enroll patients with chordomas of the base of skull, spine or sacrum; or chondrosarcomas of the spine or sacrum.  The study will also be open soon at MD Anderson. Proton beam scanning potentially allows delivery of the planned radiation dose to the tumor to a greater degree, while shaping the radiation dose to avoid important structures close to the tumor.  The study investigators believe that the higher tumor dose delivered with this technology will lead to improved tumor control and fewer side effects from radiation.

For more information about this clinical trial, click here.  To see a complete list of clinical trials open to chordoma patients, visit www.clinicaltrials.gov

Over the past several years, interest in chordoma has grown and numerous new investigators have ventured into chordoma research. During the same period, opportunities for new research have also multiplied as cell lines and animal models have become available, and key features of chordoma biology have been revealed.

The Chordoma Foundation has previously awarded seed grants to eleven investigators. Dozens of additional researchers across the world are ready to begin new chordoma research projects, but, to get started, the vast majority of these researchers need seed funding from the Chordoma Foundation. To meet this need, the Chordoma Foundation is offering peer-reviewed seed grants of up to $50,000 to support investigator-initiated projects that will advance the development of effective treatments for chordoma.

An important component of the Foundation’s comprehensive Research Roadmap, these grants are intended to enable researchers to start projects, test ideas, or generate preliminary data that could help leverage additional funding sources and lead to sustained chordoma research programs. Projects that will be supported include, but are not limited to: identifying mechanisms driving chordoma pathogenesis; characterizing potential therapeutic targets for chordoma; developing and characterizing chordoma model systems; and developing and testing therapies for chordoma.

Applications are reviewed by an independent NIH-style peer review committee comprised of subject-matter experts. Applications that are scored favorably but not funded during the initial awards cycle may be funded as additional money becomes available.

Letters of intent are due April 15th, and, for those invited to submit an application, the due date is June 3rd. Awards will be made by August 31st.

For more information, see the request for applications on our funding opportunities page.

Chordoma Foundation Executive Director, Josh Sommer, has been named by Forbes to its list of “30 Under 30,” 30 individuals under the age of 30 in each of 15 fields who are poised to change the world . “Josh is a courageous young man who refused to accept a bad hand lying down; he exemplifies the spirit of Forbes’ 30 Under 30,” said Forbes Executive Editor, Michael Noer.

Forbes collaborated with experts in diverse industries to develop a list of the brightest stars making waves in each field. Josh, representing Science & Healthcare, is highlighted on the Forbes website and in the upcoming edition of Forbes Magazine. In a video interview with Michael Noer, Josh spoke of the need to strategically allocate research dollars. “You have a lot of power,” Josh says of patients diagnosed with a rare disease.

Beyond recognizing Josh for jumpstarting the field of chordoma research and fighting to improve the lives of people affected by chordoma, his selection calls attention to the power patients have as a group. The Chordoma Foundation has made great strides under Josh’s leadership but this progress was only possible with the support of many chordoma patients, family members, and friends, and the generosity of the Foundation’s many donors. The story of the Foundation is not one person’s – it’s the story of many people who care about improving the lives of chordoma patients coming together to cure an otherwise neglected disease.

The Foundation is only as powerful as the supporters who stand behind it, and, given the rarity of chordoma, everyone in our community counts. Find out how you can help continue the momentum with these ways to take action »

The University of Pittsburgh and Dignity Health’s Barrow Neurological Institute at St. Joseph’s Hospital and Medical Center are the latest institutions to partner with the Chordoma Foundation Biobank. They join two initial partner sites – the University of California at San Francisco and the University of North Carolina at Chapel Hill – to routinely bank and share high-quality chordoma tumor tissue needed for research.

The addition of these new partner sites will significantly accelerate the expansion of the Biobank’s collection and will enable the Foundation to begin distributing samples sooner in 2013. Partnering with the Chordoma Foundation in this way signifies a strong commitment to advancing chordoma research and improving the treatment of chordoma patients. The Foundation is deeply grateful to the physicians, staff and administration at each of these hospitals for contributing to this important collaborative effort.

Chordoma patients who have surgery at these hospitals will be given the option to donate part of their tumor – only what is not needed for clinical care – to be used for research. If a patient consents, a portion of their tumor will be saved locally, and a portion will be shipped to the Foundation’s centralized Biobank to serve as a resource to the entire chordoma research community.

While these four partner sites have agreed to routinely collect tissue on behalf of the Foundation, patients can request to donate tissue to the Biobank regardless of where they have surgery (in the United States) by contacting the Biobank at 877-230-0164 or biobank@chordoma.org.

Since the Biobank was launched in April, 28 patients treated at over a dozen hospitals have contributed tissue. The Chordoma Foundation is currently working to set up partnerships with additional hospitals across the US. To learn more about the biobank and current partner sites, click here.

In the year following the Third International Chordoma Research Workshop, participants formed 30 new collaborations (thick lines) and 174 new relationships (thin lines), increasing network density by 57%. View full-size network graphs: 2011 | 2012

Measuring the evolution of a research network

When the Chordoma Foundation started in 2007, research on chordoma was at a near-standstill, and only a handful of labs spread across the globe were actively studying this rare disease. Among the most important factors that impeded progress in the field – in addition to scarcity of funding and lack of critical biological materials – was the isolation and lack of coordination among these disparate chordoma researchers.

To connect and expand the global chordoma research community, between 2007 and 2011 the Foundation hosted a series of three International Chordoma Research Workshops (ICRW) in partnership with the National Institutes of Health. In total, these meetings brought together over 150 physicians and scientists from nine countries, many of whom were new to the field of chordoma research.

Over the past five years we have observed numerous examples of new research projects being prompted by unpublished data that was exchanged, or new relationships that were formed, during the workshops. For example, at the last workshop, a researcher from Johns Hopkins who developed a mouse model of chordoma connected with scientists from the NIH who had identified approved drugs that showed promise in chordoma cell lines, leading to a collaborative drug screening project now funded by the Chordoma Foundation. However, while there is anecdotal evidence that the workshops stimulated fruitful new collaborations, we want to actually quantify the impact they have on relationships among participants.

To measure how relationships among participants change after attending a workshop, we conducted a survey immediately prior to and one-year following the 2011 ICRW asking all participants to what extent they knew each other workshop participant. A participant could indicate that he or she (i) does not know, (ii) knows of, (ii) has interacted with, or (iv) has collaborated with each other participant.

Based on survey results, 174 new relationships and 30 new collaborations were formed following the workshop. Social network analysis (courtesy of Eric Giannella, UC Berkeley) revealed that the network density (proportion of potential relationships actually established) increased by 57% and the average path length (the number of steps between any two individuals in the network) decreased by 23%.

Network density is a measure of how “close knit” a network is; it is the proportion of potential connections that are actually established. Characteristic path length is the average number of steps between any two nodes in a network.

Accelerating research by optimizing the network

Creating relationships and collaborations among researchers is not an important end in itself. It is important because each individual instance of collaboration represents investigators coming together to accomplish something that they could not do alone, and each relationship represents the potential for future collaborations or sharing of information, know-how and ideas that could lead to new research and new discoveries. Similarly, studies of scientific networks have demonstrated that higher network density (proportion of realized connections) [1-3] and lower characteristic path length (average number of steps between nodes) [4] are associated with increased innovation within the network.

Thus, the marked increase in the number of relationships and collaborations among workshop participants, the increase in network density, and the decrease in characteristic path length of the network could portend a further acceleration of progress in the coming years. Over time, we will test whether in fact the observed increase in cohesiveness among workshop participants results in an increase in discoveries, as measured by the number of chordoma-related publications produced by participants after the workshop.

To our knowledge, the effect of a scientific conference on the interconnectedness of a research community, and the productivity of that community, has never been measured. However, we think that understanding how a conference, or any other intervention, affects the dynamics of the network, could help us be smarter about how we focus efforts in the future (e.g. might we design future meetings to intentionally connect certain isolated regions of the network?). Therefore, we will administer the survey again before and after the next research workshop and intend eventually to survey the entire chordoma research community annually.

Our responsibility as a Foundation seeking to accelerate the development of new treatments for chordoma is to use the resources entrusted in us to catalyze meaningful research as efficiently and effectively as possible. The results of this survey suggest that among the possible ways to stimulate research — awarding grants, offering prizes, distributing biospecimens, etc. — convening the global research community produces a large return on investment. In light of these findings, we embrace the role of the Foundation as chief connecter within the chordoma research community, and we are doubly committed to investing in programs to facilitate communication and collaboration among chordoma researchers. The next research workshop will be held March 21-22 in Boston MA. Click here to learn more »

References

1. Singh J. Collaborative Networks as Determinants of Knowledge Diffusion Patterns. Management Science. 2005;51(5):756–770.
2. Abrahamson E, Rosenkopf L. Social Network Effects on the Extent of Innovation Diffusion: A Computer Simulation. Organization Science. 1997;8(3):289–309.
3. Ebadi YM, Utterback JM. The Effects of Communication on Technological Innovation. Management Science. 1984;30(5):572–585.
4. Fleming L, King C, Juda AI. Small Worlds and Regional Innovation. Organization Science. 2007;18(6):938–954.

The newest member of the Chordoma Foundation’s growing team, Patty Cogswell brings over 25 years of cancer research experience to her role as the Foundation’s first full-time manager of research. Patty joined the Foundation this spring from the University of North Carolina at Chapel Hill (UNC) Lineberger Cancer Center, where she served as a research scientist and lab manager for 21 years. There, she became involved in chordoma research through a collaboration between UNC, Duke, and the Chordoma Foundation. At the Foundation, Patty has assumed responsibility for the biobank, cell line and animal model repositories, prizes, and research grants. In addition to first-hand perspective as a scientist studying chordoma, Patty adds to the Foundation’s staff valuable cancer biology expertise and extensive experience managing research projects.

“I’m inspired by the innovative way in which the Foundation is addressing the need for research on this rare disease,” says Cogswell. “At the Foundation I see real opportunities to advance research on many fronts, and I’m hoping to finish my scientific career by being a part of something that really makes a difference.”

Patty’s position is supported through a fellowship of the Carolina Kickstart Program at the NC Translational and Clinical Sciences (NCTraCS) Institute, UNC’s home of the NIH Clinical and Translational Science Award. This fellowship is funded by a generous gift from long-time Chordoma Foundation supporters, Adam and Rosalind Abram, who recognized that having a manger of research on staff is critical to achieving the Foundation’s research goals, and to taking advantage of a growing number of new research opportunities. As a Kickstart Fellow, Patty maintains affiliation with the UNC Lineberger Cancer Center, giving the Foundation access to valuable resources and capabilities within the University. Patty’s work at the Foundation also provides an opportunity for the University to study the Foundation’s approach to accelerating research in chordoma, which could serve as a template for other rare cancers.

The Foundation is deeply grateful to the Carolina Kickstart Program and to the Abram Family for their strategic investment in this position, which greatly increases the Foundation’s capacity to catalyze progress against chordoma.

Meet the Foundation’s staff »