In this month’s clinical trial conversations blog, Maia and Manju review the Evaluating Radiation, Ablation, and Surgery (ERASur; NCT05673148, A022101/NRG-GI009) trial, a phase III study for patients with limited metastatic colorectal cancer (mCRC) alongside Dr. Eric Miller, principal investigator (PI) of the trial and a GI radiation oncologist at the Ohio State University Comprehensive Cancer Center. Special thanks to Dr. Miller for contributing to this blog.

Highlights of the ERASur trial:

• Who: Stage IV patients, MSS, BRAF wildtype, no liver-only metastases or mets to the peritoneum or omentum.
• What: Comparing outcomes of patients with ablative therapies + systemic therapy to systemic therapy only
• When: Active since 2023
• Where: 100 locations nationwide, additional locations added monthly
• Why: To improve overall survival for patients with limited metastatic disease

Here, we take a deeper dive into the trial with Dr. Miller.

What is the primary objective of the ERASur study?

Dr. Miller: The primary objective of ERASur is to answer this question – Do patients with limited metastatic colorectal cancer live longer if we treat all sites of disease with ablative therapy (e.g., surgery, radiation, and thermal ablation) and standard-of-care chemotherapy (a systemic therapy) or standard-of-care chemotherapy alone?

For patients with stage IV colorectal cancer that has only spread to the liver, we know that there is a benefit when the metastatic tumors are treated with both ablative therapy and systemic therapy. However, for patients with metastatic disease that has spread to sites other than the liver or who have metastases of the liver and other sites in the body, we don’t know if there is a benefit to adding ablative treatment to all sites of metastatic disease along with systemic therapy or if treatment with systemic therapy alone is enough to improve survival. 

Without a benefit to adding ablative treatment to systemic therapy, patients could spend needless extra time and money traveling to appointments or experience unwanted and unnecessary side effects of ablation therapy.

When can patients enter and what are the study inclusion criteria for patients with metastatic CRC (colorectal cancer)?

Dr. Miller: 

Patients can enter the study early by pre-registering before they start standard-of- care therapy (systemic therapy) or anytime up to completing 39 weeks of systemic therapy.

The inclusion criteria for pre-registration are straightforward:

1. a diagnosis of metastatic colorectal cancer either through a biopsy of the primary tumor or a metastatic site,
2. the tumor must be microsatellite stable and BRAF V600E wild-type (no BRAF V600E mutation present), and
3. no liver-only metastatic disease or peritoneal/omental metastasis.

Patients can register for the study as long as they have not developed new or enlarging metastases during initial systemic therapy, completed a minimum of 12 weeks and a maximum of 39 weeks of systemic therapy, and have 4 or fewer sites of disease remaining after initial systemic therapy on repeat imaging. A single “site” of disease is defined as each liver lobe (right and left), each lobe of the lungs, each adrenal gland, lymph nodes addressable in a single surgery or radiation field, and bone metastases that can be treated in a single radiation field. Importantly, there are no restrictions on the number of tumors per site. For example, if a patient has 3 tumors in the right lobe of the liver or 3 tumors in the right upper lobe of the lung, those are each considered one site of disease. The primary tumor also needs to be either already removed surgically or amenable to surgical removal. 

As of August 2024, the trial is open in the following states: Arizona, California, Florida, Georgia, Iowa, Idaho, Kentucky, Maryland, Michigan, Minnesota, Missouri, Mississippi, Montana, North Dakota, Nebraska, New Jersey, New Mexico, Nevada, New York, Ohio, Oklahoma, Pennsylvania, South Dakota, Tennessee, Texas, Utah, Wisconsin.

What treatments are being compared in the ERASur study?

Dr. Miller: Following completion of initial systemic therapy (12-39 weeks), patients who meet eligibility criteria are randomized to either total ablative therapy (TAT) plus systemic therapy or systemic therapy alone. For patients in the TAT group, the treatment team will decide on which ablative therapies are appropriate to address all areas of disease. Those therapies may include surgical removal, stereotactic body radiation therapy (high doses of radiation delivered in a precise manner to ablate the tumor), and/or microwave ablation (focused heat to kill the tumor). Following TAT, it is left to the treatment team and patient to come to a joint decision about continued systemic therapy. In both the TAT group and the systemic therapy alone group, there is a lot of flexibility regarding treatment. Patients can continue systemic therapy, transition to maintenance systemic therapy, or go on a treatment break at any time.

What are the expected outcomes or endpoints being measured in the ERASur study? 

Dr. Miller: The primary endpoint in the study is overall survival – comparing patients in the TAT group to those in the systemic therapy alone arm. We have additional secondary endpoints of event-free survival, toxicity of the treatments, and local control of metastatic disease in patients treated with TAT. Of note, we also have an optional blood collection in the study with planned future ctDNA analysis. 

How does the trial address patient participation barriers?

Dr. Miller: Leaving as many decisions as possible to the treatment team and patient is one of the ways that we have made this trial pragmatic. We also permit patients to receive systemic therapy closer to their home and not necessarily at the site where they register for the trial which helps make participation in the trial much more feasible for patients who don’t live close to a site where the trial is open. I want to acknowledge the outstanding input from Manju and her colleagues from COLONTOWN for their input in making this truly a pragmatic trial. 

To continue learning about the ERASur trial, check this X (Twitter) thread by @CrcTrialsChat, with short videos with the three Principal Investigators, and also this DocTalk of Manju with them, posted on Colontown University.  You can also view this clinical trial in Fight CRC’s Clinical Trial Finder.

Acknowledgements:
The PIs of the ERASur trial: Dr. Eric Miller, GI radiation oncologist and member of the Translational Therapeutics Program at the Ohio State University Comprehensive Cancer Center –James; Dr. Paul Romesser, radiation oncologist and early drug development specialist, director of Colorectal and Anal Cancer, Department of Radiation Oncology, at the Memorial Sloan Kettering Cancer Center, New York; and Dr. Kate Hitchcock, Clinical Associate Professor, Department of Radiation Oncology, University of Florida Health Cancer Center.

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.  

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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