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FDA program helps patients access experimental treatments

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The US Food and Drug Administration (FDA) determines whether any particular drug may be prescribed by doctors. It’s normally a years-long process to get a drug approved, across multiple phases, first to ensure a drug’s safety, then to determine its efficacy, and finally to assess its effectiveness compared against existing “gold-standard” treatments. Yet in some cases, patients with brain tumors and other serious conditions can get permission to try treatments that haven’t yet gone through this process, thanks to the FDA’s Expanded Access program.

Expanded Access, which is sometimes called “compassionate use,” due to its roots in offering drug options to terminally ill patients, gives patients a way to access investigational or experimental treatments outside of the structure of a clinical trial. In the past, clinical trials were the only way to access experimental treatments. According to the FDA, Expanded Access is for patients “with an immediately life-threatening condition or serious disease or condition to gain access to an investigational medical product (drug, biologic, or medical device).”

Treatments through Expanded Access remains something that is carried out under the supervision of your doctor, and so discussing all of your options with your neuro-oncologist remains the first step. Whenever possible, your doctor will probably recommend clinical trials before expanded access, because clinical trial drugs may be better understood from the perspective of safety, dosing, side effects, and drug interactions. Furthermore, data collected in clinical trials contributes to global progress against the disease.

Nevertheless, many brain tumor patients may be in a situation where standard treatments have been exhausted and clinical trial eligibility cannot be met. In those cases, Expanded Access might be the best or only way to use a drug that could help.

The program works like this:

  1. A doctor asks a drug company to provide an experimental treatment.
  2. The doctor submits the treatment plan to an Institutional Review Board (IRB), who act as a check on patient welfare and ensure that the patient can properly give their informed consent.
  3. The doctor and the IRB submit the request to the FDA, who approve most requests that have gone through the appropriate steps.

One obstacle to Expanded Access is that many doctors have limited experience going through the process. To remove roadblocks, the FDA launched an initiative in 2019 to make it easier for doctors and patients to take advantage of the program. The FDA’s oncology staff now run a call center for doctors wishing to submit Expanded Access requests on behalf of their patients. FDA staffers will now help the doctor with paperwork, drug company contacts, and IRB proposals.

While no patient hopes to find themselves in a position where throwing a Hail Mary pass seems like the best option, it remains an unfortunate reality that many brain tumor patients reach that point. When other approaches seem exhausted

Breaking Down a Glioblastoma Diagnosis

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Written by Head for the Cure Ambassador, Dr. Simon Khagi.

Dr. Khagi is an Assistant Professor of Medicine and Neurosurgery at the University of North Carolina, Director of the UNC Neuro-Oncology Program, and the Director of the UNC Brain Metastases Program.

Everyone approaches the diagnosis of a brain tumor in their own unique way. After being told of their diagnosis, patients with a glioblastoma can have a range of emotions. If they had prior knowledge of their disease before meeting me for the first time, they may have already taken the time to “Google” what this may mean to them. However, each individual glioblastoma can be as different and unique as the patient that is diagnosed with it.

A glioblastoma (GBM) is a cancer. Occasionally, these may be referred to as tumors. However, the word tumor implies a very different biology and can be disingenuous to the actual implications of being diagnosed with a GBM. Many patients may hear the word tumor and think that it can be readily removed given that it’s distinct and separate from the rest of the brain. The biology of a GBM varies greatly from one patient to another, but we know that these cancers are by no means confined to a solitary ball of cells that slowly gets larger. A GBM has the propensity to spread and diffusely infiltrate various parts of the brain. These areas of disease may not be readily apparent on a brain scan.

Imaging

When patients first present with their symptoms, some form of brain imaging is obtained to determine the cause of their complaints. It may start out with a computer tomography (CT) scan followed by a magnetic resonance imaging (MRI) scan. The diagnosis of a GBM cannot be made based on imaging alone; in fact, many times doctors may need to scan the entire body to rule out the possibility that a brain lesion is not part of a metastatic cancer arising from a different organ. If there are no other areas of disease within the body, the likelihood that the brain lesion represents a GBM is much higher. However, obtaining tissue is key in determining any further course of action.

Surgery

After being given medications for their symptoms (usually steroids with or without antiseizure medications), patients will likely meet with a neurosurgeon to discuss next steps. Ideally, the neurosurgeon they’re meeting has some expertise in the removal of brain tumors. Depending on the expertise of the surgeon, the location of the disease, and the physical fitness of the patient, either a biopsy or a more extensive resection is performed. Studies have shown that more extensive resections can lead to longer survival for patients with GBM. However, a surgeon, no matter how skilled, can never “get it all” given that, even at diagnosis, the disease has diffusely spread beyond what can be visualized during the surgery. 

Making the Diagnosis

After acquiring the tissue sample, a diagnosis can be made by a pathologist. However, that is only the beginning of how we define a GBM. In the past 20 years, there has been an extensive amount of research that has yielded insights into the “genetic drivers” of GBM. These are not the genetics of the patient, but rather of the disease itself. In a way, a GBM is a separate entity from the patient—almost like another person with their own set of genes that is potentiating its own existence. Among the more standard genes that we look at is isocitrate dehydrogenase (IDH), methylguanine methyltransferase (MGMT), and telomerase reverse transcriptase (TERT). Alterations in these genes yield important insights into the potential behavior of the disease, with the MGMT gene alterations predicting either a good or inadequate response to chemotherapy and radiation.

Next Steps

After discharge from the hospital, patients will meet the team that will be taking care of them moving forward. This team is usually comprised of a medical oncologist or a neuro-oncologist, as well as a radiation oncologist. Other members of the team may include a nurse navigator and advanced practice provider (i.e. nurse practitioner or a physician assistant). The initial meeting can be overwhelming, but sets the foundation for how a treatment plan will be formulated. Further genetic testing may be discussed and requested, with these results offering even more insight into the biological behavior of the disease and potential options for novel treatment strategies. It is important to consider the expertise of the team that is taking care of the patient. Clinicians with significant experience in the management of GBM should be a part of the treatment team; particularly, a fellowship-trained neuro-oncologist can provide significant insight regarding novel treatments, management of neurological complications, and clinical trial options. 

Centers with Clinical Trials

Clinical trials play an incredibly important role in the management of GBM. Being plugged into a center with clinical trial options at the time of diagnosis is ideal. If that isn’t an option, then having access to a center with clinical trial options at the time of disease recurrence is the next best thing. In the absence of a clinical trial at the time of diagnosis, a patient could be offered chemotherapy combined with radiation. After the completion of this combined course of therapy, maintenance chemotherapy combined with a device called Optune® may also be recommended.

Chemotherapy and Radiation

The role of chemotherapy and radiation in GBM has been established from clinical trials done almost 20 years ago, which showed a survival advantage in those patients who had chemotherapy combined with radiation versus radiation alone. The theorized mechanism of action of chemotherapy and radiation is that, when combined, the two treatments lead to DNA damage in tumor cells. If a tumor cell has damaged DNA, that cell will stop replicating and potentially die. The hope is these treatments kill off enough tumor cells and leave healthy cells alone, which would lead to a prolonged period of survival and minimal side effects for these patients.

Chemotherapy prescribed after this combination form of treatment entails taking it 5 days on and 23 days off. We call this a 28-day cycle and are repeated 6 to 12 times depending on the rationale of the treating physician. This is meant to keep the tumor from dividing; however, tumor cells may not be dying and, instead, are being kept from dividing. The addition of Optune® is also considered.

What is Optune®?

Optune®, otherwise known as tumor treating fields, is a first-of-its-kind device that is applied externally to a shaved scalp. It uses rapidly alternating electromagnetic fields (similar to radio waves) to interfere with the process of cell division. It is meant to only impact those cells that are rapidly dividing (i.e. cancer cells) and leave normal brain cells alone. In a large randomized clinical trial, the combination of Optune® and chemotherapy yielded a survival advantage compared to just chemotherapy alone.

Additional Chemotherapy

In select patients with glioblastoma who have a poorly functioning MGMT gene (i.e. methylated), there is emerging evidence that the combination of two types of chemotherapy might be more effective than one chemotherapy alone. A study out of Germany evaluated the addition of lomustine (CCNU) and temozolomide (TMZ) with radiation, followed by 42-day cycles of CCNU and TMZ, compared to the standard regimen (described above), and found that the combination prolonged survival significantly. This regimen did not include the use of Optune®. The explanation behind these promising results is that the more chemotherapy a particularly sensitive GBM sees, the better. Of course, tolerance needs to be considered when recommending such a regimen and age plays an important factor in recommending this kind of treatment approach.

Patient’s Age

Age is a very important factor when considering therapy for GBM. Given that the disease afflicts mainly people over the age of 60, a physician needs to take in to account other medical problems of the patient and their baseline “fitness” (i.e. performance status) when deciding on a course of action. For very frail patients, sometimes the best course of action is a short course of radiation or perhaps chemotherapy alone. In others, an abbreviated (i.e. 3 week) combination can be tolerable, as demonstrated in a recent clinical trial in patients over the age of 65. When treating GBM it is very important to listen to the patient and family, and really understand how they feel about potentially losing some quality of life in pursuit of a minimal amount of quantity of life. Values are important.

Importance of Clinical Trials 

Another important aspect of care to consider are clinical trials. The field of neuro-oncology is rapidly evolving and new ways of treating cancer are being tested. Some clinical trials are looking to make radiation even more potent. Other studies are assessing how best to implement immunotherapy by inducing immunological memory through peptide and DNA vaccines. And still others are looking to infect cancer cells with viruses and further stimulate the immune system with medicines that activate a robust response against the virally-infected cancer. There are hundreds of studies that are being run across the country. Any patient who is diagnosed with a GBM, should start the process early in identifying potential studies and inquiring with the center that is running the study about enrollment eligibility. There are lots of caveats to enrollment. Be sure to check out my previous post about clinical trials to understand what to expect and what questions to ask.

Empowering Patients

Living with a GBM is a journey. Along this journey, I recommend to all my patients that they educate themselves about their disease, treatment options, and potential clinical trials for the future. I consider myself a guide in the process and I hope to empower my patients to make informed decisions about their care, to balance the quality-quantity of life equation, and to be advocates for themselves.

Jenguin’s Journey – Facing a Different Front: No Good Time for Treatment

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No time is a good time for cancer treatment. Brain cancer interrupted my twenties with surgeries, chemotherapy and radiation therapy. When I was told I needed to start another course of chemotherapy nearly two months ago, I thought the timing couldn’t be any worse, with the world turned upside down from COVID-19 pandemic. But the more I thought about it, there are certainly some positives to doing chemo during this time:

  1. Work: My entire department has been working remotely from their homes, reducing my physical contact with other people. When I had to do treatment in the past, I needed to limit my exposure to others, which made collaboration difficult. Now, meetings conveniently happen over video conferencing.
  2. Face Coverings: I can wear a mask in public without a thousand stares for it because everyone else is wearing one too. And the designs I’ve seen are kind of nifty. Welcome to the world of cancer patients, everyone.
  3. Hospitals: At least the ones by me are fairly empty. No more waiting in a crowded waiting room. Of course, that means that most the time I’m alone, but let’s not focus on that.

I finished putting on my mask before exiting the car as my boyfriend dropped me off at the front entrance of our local hospital. The hand-written sign thanking healthcare workers brought a smile to my face. It was early on a Wednesday morning, which was the day designated for checking my blood counts. I proceeded through the checkpoint inside and into the quiet, somewhat desolate waiting room beyond.

“Hi Jennifer!” the lab technician chirped, before even looking down at the order. She already knew me and why I was there. The benefits of being a weekly regular. She quickly and painlessly extracted a vial of liquid from my left arm and compared the label to my wristband, all while exchanging some nice conversation, mostly about my cute dog at home.

Later that day, I received a call from the nurse with the results. There had been some causalities of war this week. Bystander blood cells destroyed in the wake of the destructive chemotherapy. I like to imagine the chemo as little elite warriors, tearing through my system to kill those wild, unwanted cancer cells. And I feel it too. My insides ache, but my fighting spirit still carries on.

Research Roundup: AI to read brain scans, progress in immune treatments

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UT Southwestern: AI may help brain cancer patients avoid biopsy

Brain tumors vary a lot, and those variances shape what kind of treatment is most appropriate. A typical journey for a person with a brain tumor goes like this: an MRI produces a preliminary brain tumor diagnosis, followed by surgery to remove the tumor, and then a biopsy—that is, a detailed chemical analysis—gives doctors a clear understanding of what key traits and mutations a tumor has. Only then can the rest of the treatment plan come together.

But researchers at UT Southwestern’s O’Donnell Brain Institute have developed a new AI that can determine the key mutations in a brain tumor from scans alone—no surgery necessary. They’re using a “deep learning” AI model, which is the same technique your phone’s photos app uses to identify faces. The technique classifies the mutation status of a brain tumor from 3D scans with over 97% accuracy. The researchers are planning some additional experiments but they hope that it will lead to more patients with gliomas able to be treated without resorting to surgery.

UF brain tumor researcher embarks on first-in-human clinical trial of novel immunotherapy vaccine

A pediatric oncologist at the University of Florida will launch the first in-human trial of a brain tumor immunotherapy treatment this summer. All immunotherapy techniques for cancer are based on the principle of teaching the immune system to recognize cancer cells as foreign invaders.

Dr. Elias Sayour has developed a technique that extracts genetic material from a patient’s own tumor, encases it in a fat-like nanoparticle, and injects the particles into patients. To the immune system, these particles look like a dangerous virus, and this triggers an immediate strike, not just on the injected particles, but on the similar-looking tumor cells.

UCalgary study finds a common vitamin may help our immune system battle a deadly brain tumour

Researchers at the Cumming School of Medicine at the University of Calgary recently published a new study that showed that combining Niacin, aka vitamin B3, with chemotherapy, helps the immune system attack glioblastoma cells, which can dramatically slow the advance of the disease.

One reason glioblastoma is so deadly is that it often hijacks the immune system, causing it to help the cancer instead of destroying it. The researchers found that this common compound can help reverse that and give drugs and the immune system the leg up it needs.

However, the lead researcher of the study, Dr. Wee Yong, cautioned that just because the findings involve a widely available compound, people shouldn’t try and dose themselves. “It’s extremely important to follow strict protocols and conduct a clinical trial first, even though this treatment involves two well-known, existing therapies. It’s important people don’t rush out and try adding niacin on their own, as we need to confirm dosage, delivery and length of time for optimum clinical results,” Yong told UCalgary News.

Therapy Harnesses Immune System to Slow Progression of DIPG Brain Tumors

Diffuse intrinsic pontine glioma, or DIPG, is one of the most common and most deadly forms of pediatric brain tumors, and it is usually inoperable because it attacks the brain stem.

Researchers at the University of Michigan have found positive results in mouse models using a gene therapy that stimulates the immune system. Normally, DIPG tumors suppress immune system activity in their surrounding tumor microenvironment. But the researchers introduced a gene called TK/Flt3L, which encourages immune activity in the region. They found that introducing this gene increases immune activity around the tumor without causing adverse side effects. This looks to be a promising step in developing future clinical immune therapies for DIPG.

Jenguin’s Journey – Facing a Different Front: Round 1

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Written by Jenny Williams (aka ‘Jenguin’) – Head for the Cure Ambassador

Change of Plans

In the brain tumor community, we “Go Gray in May” for Brain Tumor Awareness Month. I personally like the hashtag #GrayMatters, because I love the play on words.

This year, I was prepared to kick off this important month with a trip to Capitol Hill, where I was joining a bunch of fellow “thrivers” to advocate for more funding to the awesome researchers working on a cure for this disease. Unfortunately, COVID-19 foiled these plans, and the event was turned into a virtual one. Forced to stay home and send an email instead, I knew it just wouldn’t have the same impact as a meeting in-person with my members of Congress. As disappointing as this was, it turned out for the better as I headed into treatment.

Education Day

The clock was ticking, and Day 1 of my first chemotherapy cycle was quickly approaching. Beforehand, I headed back to the hospital to get my blood drawn and meet with the nurse. My boyfriend was not allowed in the building with me this time, so he dropped me off and I proceeded through the automatic doors of the cancer center. Getting used to the drill, I lifted my hat as I approached the temporary table in front, so the women behind it could scan my forehead and ask me a few questions before handing me a card with the word “APPROVED” and my temperature handwritten on it.

After a quick blood draw in the lab, I went upstairs where the waiting room had tape over some of the chairs to prevent people from sitting too close to one another. Thankfully, it wasn’t long until the nurse led me to a room where she would educate me on my treatment. I received a folder full of information on the chemo drugs and a calendar outlining my next couple months of pills, lab tests, and remote doctor visits.

Beginning Treatment

I’ve done these drugs before. It’s a well-established chemotherapy for brain cancer, a cocktail of three drugs called PCV: Procarbazine, CCNU and Vincristine. The first two are capsule form, and the third is given over IV. Last time, Vincristine gave me peripheral neuropathy, so I stopped it and continued on the other two (PC). This time, I’m foregoing the third entirely, and sticking to the first two (which is enough).

I went home to await the delivery of these two tumor-killing toxins. Bringing the packages inside reminded me of Snow White accepting her poison apple. Cycle 1 started with my first dose of CCNU, otherwise known as Lomustine. It’s an agent so strong that I have to wait 8 weeks between doses, with constant monitoring of my blood levels.

One week later, and it was Day 8 of my first cycle. I started the day off with some labs at my local hospital. A quick call from my oncologist told me everything was normal, and I finished the night with my first dose of Procarbazine, which I reluctantly take every night for 14 days.

It’s the beginning of a long journey, during a very unique time in history. I’m actually glad they are requiring face coverings in public now; it allows me to fit in with my own protective gear.