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WHAT'S NEXT

CLINICAL TRIAL FAQS

EARLY TRIAL DATA THAT MAY SUPPORT ADDITIONAL TREATMENT OPTIONS

WHAT DIDN’T WORK

IMPORTANT CLINICAL TRIALS

ADVANTAGES OF TAKING PART IN CLINICAL TRIALS

INTRODUCTION

what you will find on this page

Clinical trials are research studies that test new ways of treating, diagnosing or preventing disease. They’re how doctors find out which treatments are safest and most effective before making them widely available. Each trial follows strict rules to protect participants and is run in stages – called “phases” – so that researchers can answer different questions at each step.

Clinical trials

INTRODUCTION

Clinical trials are the main way doctors find out if one treatment works better than another. Each trial is carried out in stages, called phases. Each phase has a different purpose:

  • Phase 1: Checks if a new drug is safe for people and works out the highest safe dose. Usually involves 8–20 patients.
  • Phase 2: Looks for early signs that the treatment is working and compares results with the standard treatment. Usually involves 20–60 patients.
  • Phase 3: Compares two treatments in much larger groups to see exactly how much better one is than the other. Usually involves 300–800 patients.
  • Phase 4: Monitors how a treatment works in everyday life after it’s approved, often following thousands of patients.

Sometimes doctors can design a trial that starts as Phase 2 and moves into Phase 3 if the early results look promising. But setting up a clinical trial takes a lot of planning, time, and resources. If you need treatment quickly, it’s often not possible to wait for a trial to open, as this can take months or even years.

Advantages of taking part in clinical trials

There are a few reasons. Lung and breast cancers are much more common, which means there are more patients available to join large trials. This makes it easier to attract research funding and interest from the pharmaceutical industry. Doctors and scientists also understand these cancers better, so new treatments can be developed and tested more quickly.

Brain tumours, especially glioblastomas, are less common and more complex. This makes them harder to treat and harder to study. It’s also more difficult to get drugs into the brain because of something called the blood–brain barrier, which acts like a protective shield. All of this means progress can be slower, but interest in brain tumour research is growing.

Why are there so many new trials for lung and breast cancer but not for brain tumours?

This is called using historical controls. It sounds simple: if patients today do better than patients a few years ago, the new treatment must be helping. But it’s not that straightforward.

There are two main problems:

  1. The type of patients in trials - People who join clinical trials are often younger, fitter, and more motivated than the average patient, so they may do better anyway.
  2. Who’s allowed into the trial - Trials often have entry rules that can filter out patients with more aggressive disease. For example, one trial for a vaccine only included people whose first scan after chemo–radiotherapy didn’t show progression. This automatically removed those with the fastest-growing tumours, making the results look better than they really were.

In that example, early trial results looked promising, but when the vaccine was tested in a much larger study, it made no difference at all. That’s why comparing against historical data isn’t usually a reliable way to measure whether a treatment truly works.

Why can’t we just compare how patients do now with how they did in the past?

Important clinical trials

Optune (EF-14 trial): This study looked at adding tumour treating fields (TTF) - a device that uses electrical fields to slow cancer growth - to radiotherapy and chemotherapy for newly diagnosed GBM. Adding TTF improved survival by almost 5 months on average. Patients who used the device more consistently tended to live longer. You can read a summary of the evidence [link] or a detailed review [link].

Optune (EF-14 trial)

Stupp trial: The most important brain tumour trial to date. This large study tested adding the chemotherapy drug temozolomide to the then-standard 6 weeks of radiotherapy. Chemotherapy was given at the same time as radiotherapy and then continued for up to 6 months afterwards. This combination - now known as the Stupp regimen - improved average survival by about 2.5 months and increased the number of people alive at both 2 and 5 years. It remains the standard treatment for younger, fitter patients with glioblastoma (GBM).

Stupp trial

BR02 trial: An older study that compared two different doses of radiotherapy (45 Gy vs 60 Gy). Patients who had the higher dose lived longer. Although it’s now dated, it provided important early evidence that helped guide later research.

BR02 trial:

High-Grade Glioma (HGG)

Here are some of the key clinical trials that have shaped the way doctors treat brain tumours. Some of these studies are older and need to be interpreted with care, while others are more recent but still ongoing. We’ve included both “positive” trials (where the treatment helped) and “negative” trials (where the treatment didn’t make a difference). Often, when people ask “Why not try X?”, there’s already been a trial showing that X doesn’t work.
This trial looked at adding chemotherapy to radiotherapy for certain low-grade gliomas. Results showed a survival benefit for some patients, which helped shape current treatment approaches.

RTOG trial:

Low-Grade Glioma (LGG)

This study established treatment combinations for children and young adults with medulloblastoma, helping improve long-term outcomes.

Packer trial

Medulloblastoma

What didn’t work

These studies looked at whether giving radiotherapy earlier versus later, or at higher versus lower doses, made a difference in certain brain tumours. The results showed no survival benefit from earlier treatment or higher doses in these situations.

EORTC and RTOG trials

This large phase 3 trial tested a vaccine designed to target a specific mutation in the EGFR protein (called EGFRvIII) in patients with newly diagnosed GBM. To take part, patients had to:

  • Have an EGFRvIII mutation in their tumour
  • Receive the standard chemoradiotherapy treatment
  • Start the vaccine at the same time as their ongoing temozolomide chemotherapy
  • Over 700 patients took part, but the vaccine did not improve survival.

Looking back, one likely problem was that the earlier phase 2 trial wasn’t randomised and compared results to historical data instead of a control group. That made the results look better than they really were. When another research group compared those phase 2 patients to their own data, it suggested the apparent benefit was due to selecting patients who were already more likely to do well.

The company that developed the vaccine still exists, but no longer works in cancer research.

ACT IV trial

Increasing the dose of radiotherapy beyond the standard amount has not been shown to improve survival for patients with glioblastoma (GBM).

Dose escalation for GBM

Here are some of the larger clinical trials that showed certain treatments for brain tumours don’t work. Even when a trial is “negative” - meaning it didn’t show a benefit - it can still teach us valuable lessons about how research is done and how to design better studies in the future. Sometimes a big phase 3 trial fails because the earlier, smaller studies gave an overly positive impression. When that happens, researchers have to ask: What did we miss in the early work?

Early trial data that may support additional treatment options

  • More problems with low blood counts
  • Slightly higher risk of brain swelling

This same approach is now being tested in a larger US trial (NRG-BN011) with over 300 patients – results are not yet available.

There have also been “real-world” reports from Germany (70 patients across 5 hospitals) and the UK (40 patients across 3 hospitals, including our own) showing survival may be longer than with temozolomide alone, and that the treatment is possible to deliver in routine care.

In the UK, some hospitals now offer this combination routinely for eligible patients, but many do not.

Side effects:

Patients in this trial did better than we might expect even in the standard treatment group, possibly because they were a particularly healthy or carefully selected group.

What to keep in mind:

  • 129 patients followed for 2 years
  • Average survival: 48 months with both drugs vs 34 months with temozolomide alone

The study:

For patients with newly diagnosed MGMT-methylated glioblastoma (GBM) who are receiving chemo-radiotherapy, a small German trial (called NOA-09) suggests that combining two chemotherapy drugs – temozolomide and lomustine – may be more effective than temozolomide alone.

Combined chemotherapy (Temozolomide & Lomustine)

In the section above, we listed the main trials that support current standard treatments. These are well known to doctors working in brain tumour care.

Here, we look at some newer trials that suggest possible benefits from treatments that aren’t yet standard. The evidence for these is still developing, and results can change quickly as more research is done. Many of these studies involve small numbers of patients, so it’s harder to draw firm conclusions – especially when compared to the large trials used to set standard treatments.

For each option, we’ve included a short summary and our view on what the results might mean.

Pembrolizumab is a type of immunotherapy that helps the immune system recognise and attack cancer cells.

A small early study in 2019 looked at giving pembrolizumab before surgery (this is called “neo-adjuvant” treatment) for people with recurrent glioma. This study involved 35 patients and suggested a possible survival benefit.

However, when researchers followed this up with an additional 25 patients in 2024, they did not see the same benefit. These studies mainly aimed to understand how the drug affects certain markers in tumour tissue, rather than to prove it improves survival. At the moment, pembrolizumab is not a standard treatment for glioma.


Pembrolizumab

Immunotherapy and vaccines

The CeGaT vaccine is made in Germany and is designed to target specific markers in a person’s tumour. A retrospective study looked at 173 patients with glioblastoma who had the vaccine as part of their usual care and compared them to historical data from other patients.

Of these, 70 patients received the vaccine before their disease progressed, and there was some evidence that those who developed an immune response to the vaccine lived longer.

However, there are important limitations. People who can travel abroad for treatment are often younger, fitter, and more able to afford the costs, which can make results look better than they might for the general population. This makes it hard to be sure how much of the benefit is from the vaccine itself.

Vaccines – CeGaT vaccine

DCVax is another vaccine treatment that has been studied in a large phase 3 trial. While the trial was set up to compare patients receiving DCVax with those on standard treatment, the published results instead compared the DCVax group with patients from other, unrelated trials.

This way of presenting the results has been widely criticised because it makes the findings harder to interpret and less reliable, and was not how the trial was originally designed.

Vaccines – DCVax

PATIENT TIP

  • Small numbers: If a study only involves a few patients, random chance can make the results look better or worse than they really are.
  • Special patient groups: People who join certain trials (especially those abroad) may be healthier, younger, or wealthier than the average patient – which can make the treatment look more effective than it might be for everyone.
  • Unusual comparisons: Comparing trial results to patients from other studies (rather than to a group in the same trial) can be unreliable, because those other patients may have had different care, follow-up, or health backgrounds.

That’s why a single small or unusual study is rarely enough to change standard treatment – larger, well-designed trials are needed to confirm results.


Why small or unusual trials can be misleading

There are two main trials that look at the combination of Optune (tumour treating fields) and the immunotherapy drug pembrolizumab.

2-THE-TOP trial – Newly diagnosed GBM
This small, non-randomised trial included 26 people with newly diagnosed glioblastoma (GBM). All patients had standard chemoradiotherapy, plus Optune and pembrolizumab.

  • Median survival: 24.8 months
  • Key point: This survival time did not seem to be explained by the usual “good prognosis” factors, such as MGMT methylation.

The results have only been shared so far in summary form (not a full published paper), so more detail is needed before firm conclusions can be made.

LUNAR trial – Metastatic lung cancer
This trial looked at people with advanced lung cancer who were already receiving standard second-line treatment. A total of 276 patients took part, and half also used Optune.

  • The benefit from Optune alone was modest.
  • However, in patients who were also taking pembrolizumab as part of their standard care, the benefit was much greater.

This suggests that Optune and pembrolizumab may work better together than either treatment on its own – at least in lung cancer. This finding is why researchers are interested in testing the combination in brain tumours.

Optune + Pembrolizumab

Patient tip

  • Abstract-only results: If a study has only been presented at a conference and not yet published in full, it means other experts haven’t had the chance to review all the details. Important information about side effects or how the study was done may be missing.
  • Very small studies: When only a few patients take part, results can be strongly affected by chance or by the type of people who join.
  • Early findings can change: Promising early data often looks different when tested in larger, more rigorous trials.

That’s why doctors will usually wait for more complete data before changing standard treatment.

Why “abstract-only” or very small studies should be treated with caution

Modelling is a way of using detailed information about a tumour’s genetics to predict which treatments might work best. This is not the same as a clinical trial - it’s more like an advanced computer simulation based on research data.

Cellworks

  • Uses genetic data from the tumour (including whole exome sequencing and copy number variation) to run in-house models.
  • Has published retrospective analyses suggesting they can predict survival and whether a GBM tumour will not respond to temozolomide – even if it is MGMT-methylated.
  • Has also shown an ability to predict immunotherapy resistance in lung cancer.

ENLIGHT

  • Uses information about how genes are turned on or off in a tumour (transcriptomic data) to predict response to targeted therapies and immunotherapy.
  • Their main research paper includes some GBM patients, but there is limited detail on the GBM-specific findings.

At present, these modelling approaches are still in the early stages of development. While they may guide future personalised treatment, they are not yet part of routine care for GBM.

Modelling-based approaches

Patient tip

  • Lab studies (in vitro) test drugs on cancer cells in dishes or animal models – they don’t always translate into success in humans.
  • Modelling uses existing research and genetic data to make predictions, but these predictions need to be tested in real patients before we know if they work.
  • Clinical trials are the only way to know for sure whether a treatment helps people live longer or improves quality of life.

These early studies are important for finding new ideas, but they are just the first step in a long process before a treatment can be recommended.

Why “lab” or “computer model” results aren’t the same as proven treatments

clinical trial FAQs

In short: The idea is possible - and there are research teams trying to make it happen - but the rarity, complexity, and cost of brain tumour research mean progress is slower than anyone would like.
The blood–brain barrier protects the brain from harmful substances, but it also blocks many drugs. So even if researchers identify a genetic “target” in the tumour, getting a drug to that target inside the brain can be very difficult.

6. Even if we find the cause treatment is still hard

Brain tumour research is underfunded compared to more common cancers. The kind of detailed analysis this question suggests is expensive - it needs advanced technology, specialist staff, and ongoing data collection.

5. Funding and resources

Genetic and health data is sensitive. Using it for research requires strict consent and privacy safeguards. Not all patients agree to this, and the laws around how data can be used can slow or limit large-scale studies.

4. Ethics and privacy

Histology (how the tumour looks under a microscope) and sequencing (its genetic code) produce huge amounts of information. Bringing that data together from different hospitals, using different methods, and analysing it in a standardised way is a massive task.

3. Data is complex and hard to combine

Brain tumours are relatively rare, especially specific subtypes. To compare tumours meaningfully, researchers need large databases with complete, high-quality data - but for brain tumours, these are harder to build than for more common cancers such as breast or lung.

2. There aren’t enough patients to compare

Even tumours with the same name can look and behave very differently under the microscope and at the genetic level. This makes it hard to find a single cause or clear pattern. Some genetic changes are known to be linked with certain brain tumours, but these vary widely from person to person.

1. Brain tumours are extremely varied

Many people - including surviving caregivers - wonder why doctors don’t routinely compare each patient’s tumour in detail with the tumours of others to understand where brain tumours come from and how to treat them more effectively. It’s an understandable question, but there are several challenges:

Why isn’t there more detailed analysis of every patient’s tumour to guide treatment?

UK-focused tool specifically for brain tumour patients, with information on how trials work and how to get referred. 

Brain Tumour Charity – Find a Clinical Trial

A UK-based, patient-friendly trial search tool with simplified summaries of each trial. 

Cancer Research UK Clinical Trials Database

A European database with information on trials taking place in EU member states and the EEA.

EU Clinical Trials Register

The largest international database of clinical trials. You can search by condition, location, and trial phase. It can be overwhelming, but it’s comprehensive. 

ClinicalTrials.gov

A global platform that helps patients and doctors find clinical trials and expanded access programmes. They can work with your medical team to help you access treatments that aren’t yet widely available. 

myTomorrows

If you want to explore your options further, there are independent services and resources that can help you find and understand clinical trials, expanded access (compassionate use) programmes, and other treatment pathways. These can be useful if:

  • You’ve been told there are no more treatment options, but want to check for yourself
  • You’d like a second opinion from another doctor or centre
  • You want clear, accessible information without medical jargon

Where else can you find help with clinical trials and new treatments?

patient tip

You don’t need to wait for your current doctor to bring up these resources. You can take the information you find to your medical team, or seek a second opinion from a centre with more trial experience.

IS THERE MORE? – Exploring Beyond Standard Care

HINO SUPPORT GROUP

PATIENT-FOCUSED SEMINARS AND YOUTUBE ARCHIVE

You can keep exploring:

Looking for your next step?

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Looking into clinical trials can bring up a lot of questions and sometimes feel overwhelming.

If you’d like expert guidance to help you understand your options, whether that’s clinical trials, emerging treatments or personalised care plans, you can explore treatment options or learn more about booking a consultation:

What's next

Patients family

Access to a website like this would have been a breath of fresh air during the chaos and confusion that followed my husband’s diagnosis. Having clear, specialist-led information in one place would have helped us better understand what was happening, what options existed and how to navigate decisions with more confidence. At a time when everything felt overwhelming, clarity and compassion in how information was presented would have made a real difference. I’m really glad that this website now exists for others facing a similar situation.

Patients family

Tackling a GBM diagnosis is extraordinarily overwhelming, the stats bulldoze you & researching treatment options online is sole destroying. Having one consolidated place to connect with other patients, understand additional treatment options & potential trials & follow others journeys is incredibly comforting and very much needed. Thank you. It’s a tough journey and we only get through it by all sharing our discoveries to make each others experiences that little bit easier.  

Thank you for putting the time aside for this website. Being a caregiver to a 10momths in GBM patient I can honestly say that this website will benefit future patients enormously.

Patient

When everything changed, I didn’t want medical jargon or endless links. I just wanted clear, honest information I could actually understand.
Having it all in one place helped. Finding the information together was a huge relief. We could stop Googling and start getting a clearer picture of what was going on.
I could come back when I was ready. Some days I read a lot. Some days I couldn’t read anything at all. Knowing I could come back without pressure really helped.
Knowing more made things feel less chaotic. Understanding my options didn’t fix everything, but it helped things feel a little less out of control.
This was about more than treatment. This affected my whole life - not just my health. Seeing emotional and practical support included made me feel like that was understood. I didn’t feel like I was doing this alone. It felt like someone had already done the hard work of pulling this all together for me - and that meant a lot!

This website is an independent resource, developed by the Horizons in Neuro-Oncology (HINO) team in the UK. Initial development was supported by Dr Matt Williams and Lillie Pakzad-Shahabi, with grant funding from Novocure to support ongoing work.

HINO maintains editorial independence. While the team collaborates with a range of healthcare organisations and receives grant support from Novocure, all content is created and reviewed by the HINO team and reflects their combined clinical expertise, professional experience, and lived experience as patients and caregivers.

While content is based on UK clinical practice, much of the information may be relevant to international readers. It is provided for general guidance and should not replace medical advice from your own healthcare team.

Please use this information to support discussions with your local oncology team, or see our advice on obtaining a second opinion.