Clinical trials for discovering new treatments in earlier state diagnoses.

Clinical trials are so important for advancing our knowledge of diseases and treatments. When we talk about clinical trials, many may think of those for metastatic, or stage IV cancer survivors; however, clinical trials are just as important for discovering new treatments in earlier state diagnoses as well.

This month, we’re talking with Maia and Manju about trials for those who have stage II or III colorectal cancer (CRC).

Why is it important that patients with earlier stage CRC start to look for trials?

Manju: Great question! There may be new developments in the field that are being tested out via clinical trials that early-stage patients may only have access through trials, such as new approaches to treating rectal cancer for example, or trials looking at the clinical utility of CtDNA. In many of these cases, early-stage patients would likely be randomized to get Standard of Care (SOC) treatments for their condition or that plus the experimental intervention. Early-stage CRC clinical trials allow patients as a group to have more treatment options. Maia, did I cover the important points?

Maia: Absolutely. Stages II and III patients receive surgery with curative intent, so it’s unlikely most patients and even doctors will think about clinical trials in those cases. However, as you said, a clinical trial may provide access to a cutting-edge technology (without compromising standard of care, of course), for example: a new surgical approach; a new way to dose chemotherapy, to maximize results while minimizing side effects; a non-invasive monitoring tool, like CtDNA; an immunotherapy to prevent recurrence.

Which trials are you both excited about that the stages II and III communities should know about?

Maia: I’d like to highlight the clinical trials that aim to prevent recurrence by enlisting the immune system for that task. Our powerful immune system works constantly to recognize and eliminate cells that have damaged DNA and, hence, have the potential to become cancerous. In that sense, cancer is a manifestation of malfunctions in immunity. While surgery, chemotherapy, targeted therapy, and radiation target the cancer itself, immunotherapy is a class of treatments that works by helping the immune system recognize and attack cancer cells, as it’s supposed to do. By doing so, immunotherapies are providing durable responses for many cancers. 

For CRC patients, one type of immunotherapy is in clinical trials for early stage patients: vaccines.

iNeST RO7198457 (Autogene cevumeran) is an mRNA-based, personalized cancer vaccine, given intravenously over 12 months to stage II (high risk) and stage III CRC patients whose ctDNA test came positive after resection. In this trial, outcomes for the patients receiving the vaccine will be compared to results from patients receiving the standard of care (“watchful waiting” approach). 


Even if the vaccine is a novel agent, it is not totally unknown by now:  A prior trial used this vaccine combined with other immunotherapy for treatment of stage IV patients. Even if the clinical response was low when trying to treat patients with active cancer, the researchers determined that the vaccine does generate tumor-specific immune responses, and it is safe. The vaccine may have a role when used to prevent recurrence, with no active disease, and this trial looks forward to answering that question and, hopefully, helping many patients to keep no evidence of disease (NED).

Ad5.F35-hGCC-PADRE is another vaccine being investigated in a clinical trial for many cancers, and that recruits stages I, II, III (and even stage IV with NED) CRC patients. This Guanylyl Cyclase C Vaccine is for prevention of recurrence, in patients treated with curative intent, who have NED following front-line therapy with surgery, radiation therapy, and/or chemotherapy. Thomas Jefferson University (Philadelphia, PA) has been researching and conducting other trials with this vaccine for years, so there is literature about its safety and efficacy.

And there are more clinical trials for stages II and III patients that may help to avoid recurrence and will benefit them by providing thorough follow-up.

At risk of sounding like a broken record: There are clinical trials for every step in this journey, for those who think a clinical trial might be helpful. Clinical trials are not the last resource, nor do they always use completely unknown agents. Just keep on the loop: You or a loved one may be helped by a clinical trial.

Manju: I have been watching the early-stage CRC CtDNA space, and two trials are very interesting to me. There are many new trials coming up, so this is an exciting area to follow.

The COBRA Trial for Stage II Colon Cancer (PI: Dr. Morris) is for early stage (IIa) colon cancer patients after curative intent surgery, for whom chemotherapy is not otherwise recommended. This trial has two arms: In arm one, patients receive standard follow-up as they would otherwise. They will have regular surveillance checkups including blood collection for CtDNA testing, but they won’t get any additional treatments.

In arm two, based on their CtDNA test when they enroll in the study, if CtDNA positive, their doctor will start them on the course of chemotherapy that is best for them. If their CtDNA test is negative, then they will get regular checkups including ctDNA tests for a period of three years while they are on the study.

The Stand Up To Cancer CtDNA Trial (PI: Dr. Parikh) is for stage III colon cancer patients who have recently completed all their treatments. They get tested for CtDNA and if positive, they are randomized to 1) active surveillance, or 2)  be eligible based on their tumor characteristics, to receive either the next line of chemotherapy (FOLFIRI), or targeted therapy (if BRAF mutated or Her2 amplified), or immunotherapy if MSI-H. Those who test CtDNA negative will have active surveillance recommended for stage III patients. The purpose of the trial is to figure out if there are differences in cancer recurrence and health between CtDNA positive patients on active surveillance versus more treatments, and how more treatments affect CtDNA levels. The trial is now open at Massachusetts General Hospital, Memorial Sloan Kettering Cancer Center, Cornell, Dana-Farber Cancer Institute, and Johns Hopkins.

These trials are very interesting to me because they can tell us whether detecting recurrence early via CtDNA positivity and treating early with chemotherapy (before things show up on a scan) affects the outcomes for patients with stages II and III colon cancer. Such trials are critical to assess the clinical utility of CtDNA testing.

To learn more about clinical trials, be sure to check out our resources and download the Fight CRC Clinical Trial Mini Magazine.

You can also follow Maia (@SassyCell) and Manju (@manjuggm) on social media for the latest CRC updates!

The process of finding a clinical trial and enrolling can be daunting. Fight CRC and COLONTOWN are committed to providing the resources and tools to help the patient community identify the best option to improve quality of life, and improve access to care. 

Fight CRC works in step with the patient community to discover new ways to improve and extend lives by addressing issues like these. For clinical trials to benefit the populations they are intended for, the racial and ethnic diversity amongst participants must be increased.

Be sure to learn more about Fight CRC’s clinical trial efforts and our work addressing health care disparities.

Stay Tuned for More!

Once a month, Maia and Manju will 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.

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