This month Maia and Manju talk about clinical trials for cancer prevention. These trials are for people who have not been diagnosed with colorectal cancer (FORTE and ASPIRED-XT), as well as for those with a diagnosis of Lynch syndrome (naproxen or aspirin for LS, LS vaccine trials).

As it has been mentioned before, there are clinical trials for any and all parts of the cancer journey, as well as trials for those with average risk for developing colorectal cancer, or those with a higher risk for developing cancer (example: people with Lynch syndrome). Learning about and educating ourselves about clinical trials can be helpful in our advocacy for better health for everyone, not just patients with colorectal cancer.

Five- or Ten-Year Colonoscopy for 1-2 Non-Advanced Adenomatous Polyps (FORTE) 

NCT05080673 

What is the best timing for a repeat colonoscopy for people with one or two small benign polyps removed during colonoscopy? There is not an optimal answer for that –yet.  

The randomized FORTE/NRG-CC005 trial (NCT05080673) is looking to answer that question by evaluating different frequency of surveillance colonoscopy in individuals with a first-time presentation and removal of one to two small, benign polyps. FORTE stands for “Five- or Ten-Year Colonoscopy for 1-2 Non-Advanced Adenomatous Polyps,” and it is a study sponsored by the NCI. 

This study will measure and compare the colorectal cancer (CRC) incidence rates in the two study groups. If the cancer rates are similar to each other, then a 5-year follow-up surveillance colonoscopy exam may not be needed. Additional outcome measures include incidence of advanced adenoma, CRC mortality, and incidence of stage III to IV CRC, all at 10 years. 

The study is expected to enroll 9500 participants ages 50 to 70 years; approximately 4750 individuals will be enrolled in each study group.  

This is a clinical trial for those who are not facing CRC: Those who have a prior history of CRC are excluded from enrollment on FORTE. The trial is open to participants with just a first-time diagnosis of one or two non-advanced tubular adenomas in a colonoscopy, even to those who had that colonoscopy within four years prior to the start of this trial.  

Why would one want to participate in this trial? What would be the benefit? As participants, patients will be followed up closely, since they are being asked to provide blood, stool, and other tissues for additional studies to help the researchers better understand how colorectal cancer develops from a polyp. The trial’s findings will guide clinicians in optimizing surveillance strategies, potentially reducing unnecessary procedures and improving patient outcomes, for all the community. 

FORTE is being conducted through a collaboration with the NCI Community Oncology Research Program and the National Clinical Trials Network. NRG Oncology, which is funded by grants from the NCI, will head the trial alongside the Alliance for Clinical Trials in Oncology, ECOG-ACRIN Cancer Research Group, and SWOG. 

For more details, you can visit the patient-facing webpage for the FORTE Study, where you will find a video and plain language information about this clinical trial: https://www.nrgoncology.org/FORTE. To follow updates on social media: X / Twitter (@fortestudy) and Instagram (@fortestudy). 

ASPIRED-XT: ASPirin Intervention for the REDuction of Colorectal Cancer Risk –EXTension

NCT05056896 

The ASPIRED-XT trial is a double-blind, placebo-controlled, randomized clinical trial that takes place at Massachusetts General Hospital (Boston, Mass.). Researchers aim to measure the effects of daily low-dose aspirin on various biomarkers associated with colorectal cancer. The study focuses on understanding how aspirin impacts these biomarkers and whether age influences these effects. It is a direct extension of an earlier study: the ASPIRED trial. 

Aspirin, a non-steroidal anti-inflammatory drug (NSAID), has shown promise in reducing the risk of colorectal polyps and cancer, but the exact mechanism by which aspirin prevents colorectal cancer remains uncertain. This trial may help researchers understand the mechanisms of aspirin's anti-cancer effect, which may lead to the discovery of new specific characteristics (markers) that can be used to select patients for aspirin treatment. 

Participants must have undergone a colonoscopy within the past nine months, during which at least one polyp was removed. Since polyps are a risk factor for colorectal cancer, the study aims to determine whether daily low-dose aspirin can serve as an effective preventive measure. Approximately 160 people are expected to participate during this 3-month-long research study; Half of the participants (80) will be randomly assigned to receive a daily low-dose aspirin (81 mg), and the other half (80) will receive a daily placebo (no aspirin) capsule. 

Participants may be contacted periodically after the study (no more than one to two times annually) for up to 10 years to follow-up on additional information including any continued aspirin use or follow-up colonoscopy results. 

A Phase IIa Randomized, Double-Blinded Clinical Trial of Naproxen or Aspirin for Cancer Immune Interception in Lynch Syndrome 

NCT05411718 

This phase IIa trial at the MD Anderson Cancer Center (Houston, Texas) tests naproxen or aspirin on the normal colon in patients with Lynch syndrome. Since Lynch syndrome is a genetic condition that increases the risk of various types of cancers, especially colorectal and endometrial cancers, the goal of this study is to determine whether taking naproxen or aspirin may help prevent the development of cancerous cells in the colons of people with this risk factor. 

Participants in this trial must have Lynch syndrome. They must not have evidence of active/recurrent malignant disease for six months and be at least six months from any prior cancer-directed treatment. They will be randomly assigned to take two naproxen or two aspirin matching capsules by mouth 1 time every day for approximately 1 year. This study has “triple masking,” which means that all three parties involved in the clinical trial (participant, care provider, and investigator) will not know which treatment the participant is receiving. 

Naproxen and aspirin are anti-inflammatory drugs that may have anti-cancer effects by modulating the immune system and reducing inflammation.  

Aspirin has been shown to reduce the risk of colorectal cancer in people with Lynch syndrome. Updated analyses of a large study called the CAPP2 trial, with all participants having surpassed 10 years of follow-up, show that people with Lynch syndrome who took aspirin daily had a 35% lower risk of developing colorectal cancer than those who did not take aspirin.  

Regarding naproxen, a trial (NCT02052908) has shown recently that this common pain reliever is safe to take daily and activates immune pathways in the colorectal mucosa of people living with Lynch syndrome. 

Cancer Preventive Vaccine Nous-209 for Lynch Syndrome Patients  

NCT05078866 

This 45-participant phase Ib/II trial evaluates the safety and effect of the Nous-209 vaccine in Lynch syndrome patients. Lynch syndrome is an inherited condition, where people affected have a higher chance of developing colorectal cancer and certain other types of cancer at a young age. In Lynch syndrome, because of specific Lynch syndrome mutations, abnormal proteins called “neoantigens" that are different from normal cellular proteins are produced.  

Neoantigens are recognized by the body's immune system as foreign, and the body tries to get rid of them. Tumors arise when the body is not successful in eliminating cells with neoantigens. Nous-209 is a vaccine made with man-made copies of some of those neoantigens to see if “vaccinating” participants with Lynch syndrome can help with development of an immune response and prevent the development of tumors with these neoantigens. This trial aims to see whether the Nous-209 vaccine is safe to give to patients with Lynch syndrome, and how the immune system of Lynch syndrome patients responds to the Nous-209 vaccine. This trial may help researchers determine whether receiving Nous-209 has an effect on the development of polyps or tumors in the colon.  

Eligible participants must have a diagnosis of Lynch syndrome and have no evidence of disease for six months prior to screening and must be at least six months from any prior cancer-directed therapy. The complete list of inclusion/exclusion criteria can be found here. 

The main objectives of this trial are 1) to check the safety and tolerability of the adenoviral tumor-specific neoantigen priming vaccine GAd-209-FSP (1 prime) and MVA tumor-specific neoantigen boosting vaccine MVA-209-FSP (1 boost) when given as a single agent in participants with Lynch syndrome (LS); and 2) to see immune responses to it in the participants. 

Participants will receive the prime dose on day 1 and the booster at week 8. 

The main trial outcomes are the 1) rates of adverse-events and symptom reactivity, and 2) the rate of immunogenicity after vaccination. 

Testing a Combination of Vaccines for Cancer Prevention in Lynch Syndrome 

 NCT05419011 

A Phase IIb Clinical Trial of the Multitargeted Recombinant Adenovirus 5 (CEA/MUC1/Brachyury) Vaccine (TRI-AD5) and IL-15 Superagonist N-803 in Lynch Syndrome 

This 186-participant phase IIb trial tests whether the trivalent Tri-Ad5 vaccine in combination with N-803, an immune enhancer, works to prevent colon and other cancers in people with Lynch syndrome. There are three injections in Tri-Ad5 vaccine, which contains a different component that is in precancer and cancer cells. The idea is that vaccinating with these may cause the immune system to develop an immune response to these, so it can recognize and destroy any precancer and cancer cells that produce these components in the future. The hope is that giving Tri-Ad5 in combination with immune enhancing N-803 may lower the chance of developing colon and other cancers in participants with Lynch syndrome. 

The main objective of this trial is to find out if the combination of the trivalent adenovirus-5 (Tri-Ad5) vaccines and the immune enhancer N-803 reduce the incidence of colorectal cancer in patients with Lynch syndrome. This trial will also look at the safety and tolerability of this combination; the effect of other factors like smoking, use of pain reliever drugs and alcohol on the immune response; and the effect of this vaccine on the development of extra-colonic tumors. 

To be eligible, participants must have Lynch syndrome and part of the colon and/or rectum intact. For the complete list of inclusion and exclusion criteria, please check out the trial listing here. 

The trial has safety phase I and II parts. In the safety phase I and II, participants will get the trivalent vaccine as a subcutaneous injection at weeks 0, 4, 8, and 52. Participants also undergo standard of care (SOC) colonoscopy with biopsy at baseline, at 52 weeks, and 104 weeks. 

In the randomized control phase, participants are randomized to the experimental or placebo arms. In arm I, they will receive Tri-Ad5 SC and N-803 SC, while in arm II, participants will get the placebo subcutaneously in the same schedule as in the safety phase. They will have similar monitoring with colonoscopies. All participants will have blood sample collection throughout the study. 

The main outcome for this trial is the cumulative incidence rate of the composite endpoint of adenomas (tubular, tubulovillous, and serrated), advanced adenomas and colon cancer at 104 weeks. 

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  

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