AuthorisedTherapeutic confirmatory (Phase III)Interventional

NACRE 2_Randomized phase III study evaluating two treatment strategies for locally advanced rectal cancer in patients ≥75 years old

This research study, called NACRE 2, is for people aged 75 and over who have advanced bowel cancer. It's comparing two main ways to treat the cancer: one involves surgery (called TME) after other treatments, and the other aims to avoid this big surgery if possible, by using radiotherapy and chemotherapy (medicines like oxaliplatin and fluorouracil) to shrink the tumour. The main goal is to see how many people are alive and well after two years, and importantly, how many can avoid the major surgery related to the bowel. Researchers want to understand which treatment pathway gives the best results and quality of life for older patients.

At a glance

Status

Authorised

Phase

Therapeutic confirmatory (Phase III)

Sponsor

Unicancer

Enrolment target

160

Start

02 Feb 2026

Patients ≥75 years old with cT3/T4 rectal adenocarcinoma eligible to radiotherapy FOLFOX chemotherapy and total mesorectal excision (TME) surgery

What is this study about?

This study, called NACRE 2, is for older patients, aged 75 and above, who have a type of bowel cancer called rectal adenocarcinoma that has grown a bit deeper into the bowel wall or nearby tissues. It's an important study because doctors are trying to find the best way to treat this cancer in older people, who might have other health conditions and could find major surgery more challenging.

Currently, many patients with this type of cancer have a big operation called a total mesorectal excision (TME) to remove the part of the bowel with the cancer. This study is comparing this standard approach with a different plan. The alternative plan still uses powerful treatments like radiotherapy (targeted X-rays to kill cancer cells) and chemotherapy (cancer-fighting medicines), but it aims to see if these treatments alone can shrink the tumour enough so that major surgery might not be needed. This is often called 'organ preservation' because it tries to protect the natural function of the bowel.

The main thing the researchers are looking at is how many people are alive and without the need for TME surgery after two years. They also want to see how many people can successfully avoid TME surgery while keeping the cancer under control. By comparing these two treatment pathways, the study hopes to find out which one offers the best balance of effective cancer treatment and a good quality of life for older patients.

Key takeaways

This study is for people aged 75 and over with advanced bowel cancer.
It compares standard surgery with a plan to avoid major surgery if possible.
Treatments include radiotherapy and chemotherapy.
The main aim is to see which approach works best for older patients, focusing on survival and avoiding surgery.
Your health and quality of life are key considerations.

Who may be eligible?

This study is specifically for people aged 75 and older.

You would need to have been diagnosed with a type of bowel cancer called rectal adenocarcinoma. This cancer needs to be at a stage where it has grown into the deeper layers of the bowel wall or into nearby lymph nodes. Your doctors would also need to feel that you are generally well enough to have radiotherapy, certain chemotherapy drugs, and potentially major surgery.

If you're unsure if you meet these initial criteria, it's always best to discuss it with your cancer care team, as they have all your medical details.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

Are you 75 years old or older?
Have you been diagnosed with locally advanced rectal adenocarcinoma?
Are you considered by your doctor to be well enough for radiotherapy, certain chemotherapy, and possibly surgery?
Are you able to attend regular appointments for treatment and follow-up scans?

Answer every question to see your result.

What does participation involve?

If you decide to take part in this study, you would first be randomly assigned to one of two treatment groups – like flipping a coin for fairness. One group will follow a treatment plan that involves standard surgery (TME) after receiving radiotherapy and chemotherapy. The other group will also receive radiotherapy and chemotherapy, but their care team will try to avoid major surgery if the cancer responds very well.

Throughout the study, you would attend regular appointments for your treatments, which include radiotherapy and specific chemotherapy drugs (like oxaliplatin and fluorouracil). You'd also have regular check-ups, scans (such as MRI and CT scans), and examinations (like endoscopic evaluations and digital rectal exams) to see how the treatment is working and monitor your health. The researchers will be looking at your progress over at least two years. The total time you're involved in the study's follow-up will be decided by your care team.

Potential risks and benefits

Taking part in a clinical trial offers potential benefits, such as receiving state-of-the-art care and access to new treatment approaches that might be more effective or have fewer side effects than standard treatments. You would also be contributing to medical knowledge to help future patients. However, there are potential risks, including side effects from the radiotherapy and chemotherapy, which can vary from person to person. As with any medical treatment, there's no guarantee the treatment will work for you, and some treatments may have unexpected side effects. You are always free to withdraw from the study at any time, for any reason, without it affecting your usual medical care.

Locations (1)

Some site locations are approximate. We're improving this — please verify with the trial team before travelling.

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Unverified
France

Common questions

What is 'locally advanced rectal cancer'?

It means bowel cancer in the lower part of your gut (rectum) that has grown a bit deeper or into nearby glands, but hasn't spread widely to other parts of your body.

What is TME surgery?

TME stands for Total Mesorectal Excision. It's a major operation to remove the part of the bowel with the cancer, along with surrounding tissue, to try and get rid of all the cancer cells.

What does 'organ preservation' mean in this study?

It means trying to treat the cancer with radiotherapy and chemotherapy so effectively that you might not need the major TME surgery, aiming to keep your bowel functioning as normally as possible.

Will I definitely avoid surgery if I'm in the 'no TME' group?

The goal is to avoid surgery if the cancer responds very well to other treatments. However, if the cancer doesn't shrink enough or grows again, surgery might still be recommended to ensure the best possible outcome.

What kind of chemotherapy medicines are used?

The study uses a combination of chemotherapy drugs including oxaliplatin and fluorouracil. Your doctor will explain how these work and what to expect.