If you want to learn more about clinical trials for colorectal cancer, but feel intimidated or overwhelmed by the science and research, this fireside chat about clinical trials is for you.

Our two clinical trial champions, Maia Walker, Lead Curator of the Fight Colorectal Cancer Clinical Trial Finder, and Manju George, Scientific Director of COLONTOWN, have both long been promoting education about clinical trials for the colorectal cancer community.

In this month's Clinical Trial Conversations blog, Maia and Manju discuss why clinical trials are important at every stage – not just as a last resort; the importance of knowing your tumor biomarkers; what to look for when searching for a clinical trial; as well as ways for patients to stay informed about clinical trials to treat colorectal cancer; and so much more educational information to help patients, caregivers, and loved ones make informed decisions about their treatment options.

We know there is already a standard of care for colorectal cancer. Why would patients and their advocates want to learn about experimental treatments too? What is your personal experience?

Maia:

I’d say that learning about clinical trials can help cancer patients and their advocates to make more informed decisions about their treatment options, from the moment of diagnosis. 

My personal experience is that many patients start to learn about clinical trials only after the second or third line of treatment, in the case of metastatic disease, and that most patients with earlier stages (I to III) may not read or even be aware of research studies. That often happens because of misconceptions about clinical trials. In those cases, some trials that might be of interest for patients go under their radar, and some regret this later.

"We say it often, because it’s true, but clinical trials are not a last resort."

–Maia Walker, Lead Curator of the Fight Colorectal Cancer Clinical Trial Finder

Maybe there was a trial for those just diagnosed to try a non-surgical approach or receive immunotherapy along with surgery to prevent recurrence, for example. Some patients receiving chemotherapy would have participated in a trial with a supplement or drug, given along the standard of care, to prevent certain side effects from chemo if only they had known such a trial existed. Others with metastatic disease would have appreciated receiving immunotherapy as part of the first-line therapy or a standard of care drug at a lower dose than usual, with less side effects.

As advocates, we want patients to have all the pertinent information, from as early as possible so they can learn about clinical trials and participate early, later, or never. It is a personal decision, depending on particular circumstances, so each case is unique.

Manju:

Current colorectal cancer treatments are quite limited for metastatic disease with only three or four effective lines of therapy available to patients. The earlier treatment lines are quite effective and while patients are on them, they usually think that the remaining lines of treatment will be as effective with similar response rates (how many people out of 100 respond to these therapies) and duration of responses (how long these treatments can keep their disease stable or shrink it). But this is not the case. After the first two lines of therapy, the remaining ones are effective only for a smaller proportion of patients or are effective for a much shorter time. As patients progress through these lines of therapy, their bodies bear the brunt of cumulative treatment side effects and disease progression. One of the best ways to expand on treatment options is to learn about clinical trials and how they may help expand what’s available to patients. 

As Maia wrote, there are clinical trials at every step of the journey. Incorporating appropriate clinical trials along one’s treatment journey can enable chemo breaks and allow the body to rest without being exposed to chemo side effects, for example, while the patient is on a trial with a targeted therapy combination or an immunotherapy combination.

Most patients look for trials after they have exhausted standard of care options and by this time because of how beat up their body is and how wide spread the disease is, they might not be eligible for clinical trials. Learning about clinical trials early on can allow patients to work with their care team to figure out how best they can include clinical trials as part of their treatment strategy.

"Your care team may tell you that you have many options and don’t need to think of a clinical trial at this time. However, with limited options of treatments for colorectal cancer, it is important for patients to let their care team know that they want to include clinical trials as applicable in their treatment journey."

–Manju George, Scientific Director of COLONTOWN

For patients with stage I through III colorectal cancer, there are many trials, which test newer approaches to treatment. This may mean being on a trial, which uses ctDNA testing for surveillance, or for escalation of therapy in patients most likely to progress to stage IV, or one that uses a transanal excision type of less invasive procedure to remove their tumors. These tests and procedures may not be available outside of clinical trials. So being on a clinical trial may enable earlier access to a promising experimental strategy that may take years to become commonplace in regular practice.

Knowing your tumor biomarkers (mutations, microsatellite status) is necessary for standard treatment of colorectal cancer. Does this information help in the search for a clinical trial?

Manju:

Yes, knowing your tumor biomarkers is important when looking for trials as well. Even though there are very few actionable targets – colorectal cancer mutations against which targeted therapies are available, knowing if you have these mutations can be a life-changer. For example, if your tumor is microsatellite instability-high (MSI-H), immunotherapy and trials with combinations of immunotherapy and other agents can be effective for you. 

With microsatellite stable (MSS) colorectal cancer, if your tumor has a BRAF V600E mutation, there are trials that target this mutation. If your tumor has an HER2 or ERBB2 amplification, there are clinical trials for you. Same with KRAS G12C and KRAS G12D mutations now.

If your tumor is wild type for RAS/RAF or unmutated for RAS/RAF, there are trials for you. So knowing your tumor biomarkers can help find trials that may be best-suited for you. Like how knowing your shoe size or dress size can help you find shoes or dresses that fit you, your tumor biomarkers can help you find trials that may be the best fit for you.

What to look for when searching for a clinical trial?

Maia:

When looking for a clinical trial for colon or rectal cancer, the first filtering should be for stage (I, II, III, or IV) and for microsatellite status (MSS/ pMMR or MSI-H/ d MMR). Biomarkers are something to consider, just as Manju said.

If there is some currently targetable mutation/alteration present (KRAS, BRAF, HER2, NTRK), trials centered on them should be considered. However, it is important to remember that many clinical trials are “mutation agnostic” – that is, no particular mutations are being targeted. This happens with most immunotherapy-centered trials. Immunotherapy is a treatment that uses a person’s own immune system to fight cancer. Instead of targeting a tumor or its mutations, immunotherapy can boost or change the way the immune system works so it can find and attack cancer cells.

Another aspect to take into consideration when looking for clinical trials is what prior lines of therapy are required. It is a myth that clinical trials are the last resort: Many studies take only patients who have not received third-line therapy yet, or even require patients who had not any line of therapy for metastatic disease, for example. As mentioned above, there are trials for patients just diagnosed, “treatment naïve.”

Finally yet importantly, location for the clinical trial is often a key aspect for most patients. While some studies will cover travel and lodging expenses (like those at the National Institutes of Health (NIH)), that is not often the case. Then, many people would favor trials that take place not too far away from home, or in another state where they have family or friends who can support them. Time involved is also something to consider. Logistics play an important role when considering a clinical trial.

Are there potential risks or downsides of clinical trials?

Manju:

Yes, cancer clinical trials test experimental therapies to see if these drugs are safe and effective in people with cancer. The reason these trials are run is because we don’t yet know if these new drugs being tested can help shrink tumors. A clinical trial is the way to collect this information. This means that there is the possibility that drugs being tested may turn out to be not as effective as expected, and your tumors may continue to grow while you are on a trial. This is why you will have frequent scans and blood tests to find out how your tumors are responding to treatment while on a trial. 

Since lots of information on side effects of drugs being tested in early phase trials may be unknown, patients on the dose-finding part of trials may experience side effects including mild, severe, or very severe side effects. However, clinicians running trials take many steps to ensure patient safety. Each clinical trial goes through a long process of institutional regulatory approval to make sure participants on trials are protected, and there are many measures in place to ensure patient safety. 

Phase I trials may have drugs that have not been previously tested in humans, so these trials are likely to have drugs with not as known side effects. Even if it’s a yet untested drug in humans, there are extensive safety and toxicity studies done in animal models before a drug advances to testing in humans. As a drug or combination progresses to phase II and III, it is very likely that a lot is known about side effects, and there are effective strategies for dealing with them. It is good to remember that standard of care treatments also have side effects, but clinicians have a lot of experience managing them. 

In phase III trials, patients may get randomized to an arm, which does not include the experimental treatment, but instead get on the standard of care arm. If patients were keen on getting the novel experimental therapy, there is the risk that they might not get that particular arm in a randomized trial.

What are the potential benefits of participating in a research study?

Maia:

First, the access to potentially more effective treatments: Clinical trials often involve testing new treatments or combinations of treatments that have not yet been approved by regulatory agencies.

"Participating in a clinical trial may give patients access to these potentially more effective treatments before they become widely available."

–Maia Walker

For example, let us consider trials investigating how fruquintinib works for metastatic colorectal cancer. Fruquintinib is an oral targeted therapy that selectively blocks VEGFR 1, 2, 3. That means that it only blocks those particular signaling pathways involved in angiogenesis (angiogenesis is the formation of new blood vessels, which is imperative for tumor growth and metastasis).

Fruquintinib was approved in China for the treatment of metastatic colorectal cancer (mCRC) in 2018 and had been fast-tracked by the U.S. FDA in 2020. Since then, more than 30 trials have investigated this drug in different combinations or compared it against several agents.

The FRESCO 2 is a phase III clinical trial testing fruquintinib that takes place in Asia, EU, and the U.S. It recruited patients who already had received many treatments, including the third-line therapies regorafenib (Stivarga^®) and trifluridine/tipiracil (TAS-102, Lonsurf^®). Other recruiting criteria were also quite inclusive, so more patients with limited or no other treatment options were able to participate.

Last year, at ESMO 2022, researchers reported study results. The overall survival (OS) was 7.4 months for patients treated with fruquintinib vs. 4.8 months in the placebo arm, while the median progression-free survival (PFS) was 3.7 months with fruquintinib compared to 1.8 months in the placebo arm. Main side effects are hypertension, and 6%-7% of patients experienced hand-foot syndrome and asthenia (abnormal weakness or loss of energy).

These results represent a statistically significant improvement relative to controls. It is not a cure, but it is one more option for treatment that is likely to be approved for standard of care treatment this year, in the U.S. By participating in this trial or others that involve fruquintinib, some patients have access to it before approval.

I started to keep an eye on colorectal cancer clinical trials about 10 years ago, when regorafenib, TAS-102 and anti PD-1 inhibitors (for those with metastatic MSI-H CRC) were not approved for colorectal cancer treatment. I remember friends from forums looking to participate in them, some participating. Those agents are now part of the standard of care.

Some of those patients benefited directly from participating, but many did not. However, that leads us to another, second potential benefit from participating in a research study. By participating in a clinical trial, patients can help advance medical knowledge about cancer and potentially benefit future cancer patients. Every patient achieves that, regardless of the results: They contribute to the advancement of cancer treatment. We could mention a third potential benefit: an emotional benefit, which contributes to well-being, despite the dire circumstances. Participating in a clinical trial can give some patients a sense of empowerment and control over their treatment.

How can patients stay informed about the latest news related to clinical trials to treat colorectal cancer?

Manju:

Attending oncology meetings like ASCO-GI, Annual ASCO, AACR, etc. is one way to stay updated about clinical trials. Many of these meetings have a virtual component that allows colorectal cancer patients and caregivers to attend it from any part of the world. Twitter is a great way to stay connected to news in colorectal cancer oncology. The hashtag #CRCSM can be used to search for the latest colorectal cancer-related information on Twitter. Many clinicians who work on and treat colorectal cancer are active on Twitter and most meetings have meeting hashtags. Most new results from meetings, as well as journal articles are discussed on Twitter, and it is possible to learn about different viewpoints around the latest results by following oncologists, surgeons, and radiation oncologists on Twitter. 

COLONTOWN University (CTU) is the educational arm of COLONTOWN. It has the Clinical Trials Basics Learning Center section which introduces colorectal cancer patients and caregivers to clinical trials. The CTU Lecture Hall is another place to learn about enrolling clinical trials. I invite leading clinicians to talk about work they do, as well as to discuss results of clinical trials that have been recently presented at meetings or published as peer reviewed articles. CTU has a Featured Trials section, where enrolling trials relevant to colorectal cancer patients are presented.

The Tom’s Science & Trials School neighborhoods in COLONTOWN are an excellent place to learn about clinical trials. There are eight groups where clinical trials are discussed, and it is strongly recommended that patients and caregivers join those relevant for them, focused on MMR (MisMatch Repair) status or mutations. In addition, the Alanna Project is a patient-created resource that collects self-reported information on trial participation by members and can be a great place to learn about other people’s experiences with clinical trials. 

COLONTOWN’s Clinical Trials Searching Safari workshop is a four-week virtual course for members and is intended specifically for patients and caregivers who are considering clinical trials in their future but are potentially overwhelmed and don’t know where to start. The course brings the abstract, academic topic of trials to a practical, individual level by focusing on what a potential trial participant needs to understand coupled with a process and tools (including the FIGHT CRC Trial Finder) to use to be able to identify and assess trials in the context of their individual needs, goals, constraints, and decision-making. 

I organize a monthly #CRCTrialsChat TweetChat around topics of interest to colorectal cancer patients and caregivers on Twitter. These are one-hour sessions with clinician moderators that start with basics around the topic and end with enrolling clinical trial information. A wakelet link of previous tweetchats can be found at https://wakelet.com/@CRCTrialsChat257, including the March 2023 session on RAS mutated stage IV colorectal cancer. CRCTrialsChat sessions also cover clinical trials basics and introduce people to clinical trials. One of the previous sessions of CRCTrialsChat covered the Fight CRC Clinical Trial Finder and discussed how to use it.

Maia:

Fight CRC's Colorectal Cancer Clinical Trials page is a great place to start. Additionally, the Clinical Trials Brochure, Your Guide in the Fight, Clinical Trial Finder, Clinical Trial Conversations Blog, and @FightCRC Twitter are helpful, educational, patient-friendly resources to help you navigate finding a clinical trial that may benefit you.

The Fight CRC Clinical Trial Finder, Powered by Patients, serves patients and their caregivers with a curated list of potential clinical trials for MSS mCRC, for them to subsequently discuss with their medical team. The tool is an enhanced version of a spreadsheet begun by stage IV patient and scientist Dr. Tom Marsilje.

Reading about "cancer breakthroughs" in newspapers, social media, and online can be misleading because the information provided in such articles may not necessarily apply to the specific type of cancer that a patient may have. For example, a breakthrough in treating lung cancer may not necessarily be applicable to a patient with breast cancer or colon cancer. Moreover, the biomarkers, genetic mutations, and other characteristics of the cancer cells can also differ from one colorectal cancer patient to another, making it difficult to generalize about treatments and their effectiveness. It is also important to consider the quality and reliability of the sources providing the information, as some news outlets may prioritize sensationalism over accuracy when reporting on scientific advancements.

Therefore, it is important for patients and their loved ones to be cautious when interpreting news about cancer breakthroughs and to always consult with their health care provider to determine the best course of treatment for their specific case. 

What other resources are available to a patient who wants to know more about clinical trials?

The section about clinical trials at Cancer.Net, from the American Society of Clinical Oncology (ASCO), offers comprehensive information and links to many resources for people with cancer, families, and caregivers. 

If you or your loved one are searching for a clinical trial for cancer treatment, including colorectal cancer, these are the main trustworthy resources:

National Cancer Institute (NCI) Clinical Trials: Clinical trials that are sponsored or otherwise financially supported by NCI (part of the National Institutes of Health, NIH) and that are taking place at many locations across the United States, Canada, and internationally. The NCI's Cancer Information Service can also provide a tailored clinical trials search that you can discuss with your doctor. To reach them call 1-800-4-CANCER (1-800-422-6237) and select option 2. This is a free service. Keep in mind that the search results do not replace advice from your doctor.

Center of Cancer Research (CCR) at the NIH: Clinical trials that take place at the NIH Clinical Center in Bethesda, Maryland. They are open to patients with cancer, regardless of where they live in the United States. Once a patient is enrolled in a clinical trial at the Clinical Center, medical care is free.

ClinicalTrials.gov: This is a searchable registry and results database of federally and privately supported clinical trials conducted in the United States and around the world.

Stay Tuned for More!

Once a month, Maia and Manju spend time unpacking important research trials, tips, and advice for our community. Be sure to subscribe to sign up with Fight CRC and join COLONTOWN’s online community to continue receiving the most relevant updates in the CRC world!

You can also follow Maia (@sassycell) and Manju (@manjuggm) to stay updated on research and trials and visit ClinicalTrials.gov for more information on trials.

Clinical trials are critical to finding a cure for colorectal cancer. As an advocacy organization dedicated to supporting and empowering a community of patients, caregivers and families, Fight CRC has partnered with COLONTOWN to deliver a monthly blog series highlighting everything patients need to know about clinical trials and the best treatment options available. 

In this series, we hope to cover promising trials that are enrolling, lessons learned from past research, logistics and resources to joining a clinical trial, and provide relevant and timely updates for our colon and rectal cancer community. 

Be Sure to Check Out These Fight CRC Resources:

Clinical Trial Finder

• Colorectal Cancer Clinical Trial Finder
• Colorectal Cancer Clinical Trials Brochure  

More Clinical Trial Conversations

• Clinical Trials for Early-Stage Colorectal Cancer or Minimal Residual Disease
• 2023 GI ASCO Clinical Trial Studies
• ESMO 2022 Research Update: A Patient Research Advocate Viewpoint
• Recruiting Phase III Clinical Trials for Colorectal Cancer
• Clinical Trials That Involve Surgery

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