People across the world are mourning the death of Apple co-founder Steve Jobs, who passed away Wednesday, Oct 5, following a battle with pancreatic cancer. Jobs' death has turned attention to rare form of cancer, for which the U.S. Food and Drug Administration this May approved a new drug - the first new option in nearly 30 years. Learn more about the drug, everolimus, and how it's helping patients with pancreatic neuroendocrine tumors.
Not many emails make you cry. But tears of joy rolled down Carmen Jacobs' face when she read that the drug everolimus had been approved by the U.S. Food and Drug Administration (FDA) for patients with pancreatic neuroendocrine tumors (pNET).
She considers this treatment one of her biggest efforts as a research nurse, and this news meant it had just been delivered to patients everywhere. It's a much-anticipated arrival, since this is the first new treatment option for these patients in nearly 30 years.
"I was there when Dr.Yao treated the first patient in the very first clinical trial about six years ago," says Jacobs, research nurse supervisor, Gastrointestinal (GI) Medical Oncology, who also worked on each subsequent trial. "I was so happy when I got his message saying it was approved. Now all of these patients have access to a new treatment that provides more hope for a longer and better life."
One patient produces the light bulb moment
What made James Yao, M.D., think of using everolimus, an organ transplant rejection drug, for his cancer patients?
"It goes back to one specific patient," says Yao, associate professor, GI Medical Oncology. "I was treating this young woman in her early 20s who had two rather rare diseases. I began looking for similarities in the diseases to see if a commonality might present a treatment target."
The young woman had pNET, which is much less common than adenocarcinomas -- the more common and more aggressive form of pancreatic cancer. She also had tuberous sclerosis, a rare, multi-system genetic disease that causes several types of tumors to grow in organs throughout the body.
Many of our bodies' normal and disease processes result from a chain of events, similar to a relay race. And there are lots of "tracks" in the body called signaling pathways.
Both diseases have malfunctions in the track called the mTOR signaling pathway. (mTOR stands for mammalian target of rapamycin.) mTOR is involved in nutrient sensing, energy metabolism and signaling downstream of various receptors. Yao theorized that a drug that targets this pathway could trick the tumor into thinking it was starving.
"mTOR inhibitor drugs, which evolved from a discovery on Easter Island, have an interesting history and range of applications," Yao explains. "When we started, mTOR inhibitors had been approved to help prevent rejection in kidney transplant patients. A few were being explored to coat heart stents and for cancer."
It takes a village to run a clinical trial
Yao's idea was the first of many steps involved in conducting the clinical trials that resulted in an approved new treatment for pNET patients.
The first trials, called Phase I and II trials, include small numbers of patients. They ensure the proposed treatment is safe, and they provide early evidence of whether or not the treatment will work.
The protocol is the map for clinical trials. It's critical, because once it's approved, it must be followed explicitly. People with different expertise work with the physician to develop and manage the protocol.
"We work as a team on the administrative aspects of clinical trials," says Yvonne Lassere, manager of clinical protocol administration in GI Medical Oncology. "Our regulatory and financial team, along with the research nurses, helps review the protocol's feasibility, including the financial and technical aspects of each project. Our goal is to identify and correct potential challenges and to provide the physicians the assistance needed to obtain Institutional Review Board (IRB) approval on a study as smoothly as possible."
In addition to these collaborations, there are interactions with other institutional groups such as Protocol Research, Clinical Research Finance and Legal. There also are negotiations with external groups, such as trial sponsors.
As the name implies, there's no guarantee a trial will succeed. When an investigator comes up with an idea, such as in Yao's trial, a pharmaceutical company might offer its drug at no cost, but won't always provide support for the full cost of conducting early phase trials.
MD Anderson offers institutional support to help our investigators explore novel ideas.
For example, Yao credits our Investigational New Drug (IND) Office for helping him navigate the requirements mandated by the FDA for investigator-initiated trials such as his.
"Things really have changed in the last 10 years. The FDA now holds academic institutions to the same requirements as industry, so we're here to help our physicians meet all these obligations," says Agueda Cohen, M.D., medical monitor, IND.
Once Yao's protocols were approved, work remained before patients were enrolled.
"Some might think that research nurses only take care of patients enrolled in trials," Jacobs explains. "But I have many responsibilities before the trial begins, including reviewing the protocol, creating educational materials and educating staff and patients about the trial."
"Conducting clinical research is complex," Yao says. "I'm grateful for the support of many people here who make it possible to pursue my research."
What we're all about: research that improves care
The Phase II proof-of-concept trial was conducted at MD Anderson. Given the positive results, the treatment moved to a Phase III trial. Pivotal Phase III trials are the last step before approval. They involve more patients and, given their expense, typically are sponsored by companies or large cooperative groups.
Since pNET is rare, facilities around the world joined the trial to enroll enough patients. Yao led the international effort.
When the news came out that the FDA had approved everolimus for pNET patients, a common response was: "This is what MD Anderson is all about."
"We focus on all cancers. Our patient volume and research resources make us uniquely positioned to conduct this type of research, especially for rare cancers," says Raymond DuBois, M.D., Ph.D., provost and executive vice president. "Dr. Yao's outcome is what we're all working toward: changing the standard of care for cancer patients."
Until May 4, 2011, pNET patients had one treatment option: chemotherapy that was highly toxic. Today, they can take a pill once a day that delayed cancer progression for an average of 11 months for those taking everolimus in the trial. This was a substantial improvement. Those who weren't taking everolimus had their cancer progress, on average, in 4.6 months.
"Most of our patients tolerated the pill very well, so their quality of life was greatly improved using this drug," says Physician Assistant Jeana Garris. "Some patients from our early trials have gone three years without their cancer progressing. It's wonderful that now we can offer this to all of our pNET patients."
One patient on the trial confirms that and more
"I was thankful to have an option other than the standard chemotherapy," William Settle says. "I responded very well and right away. It was kind of miraculous."
Although Settle eventually had to be taken off the drug, he's thankful for the treatment.
"I think the drug ran its course of effectiveness for me, but Dr. Yao had another treatment for me, and I've been stable since then," Settle says. "I credit being here today to Dr. Yao, Carmen and all of those who've helped me. I'm very grateful."
Further advances being studied
Yao's far from finished. "It's been amazing to have taken this from the first patient treated to presenting before the FDA Oncologic Drugs Advisory Committee. We continue to explore things such as combination therapies and ways to tailor treatments and timing to produce that best outcome for patients," Yao says.
Our clinical trials database includes detailed information on current studies.