A pragmatic randomized controlled trial of physician’s-choice systemic anticancer therapy versus best supportive care in patients with end-stage advanced solid tumors: the TRUE trial protocol

When a person has advanced cancer that has spread throughout the body, doctors often reach a point where the standard medicines designed to fight the tumor no longer work. At this stage, the medical community faces a difficult choice. One path is to continue trying different drugs, hoping that one might still shrink the cancer or slow its growth, even though the odds are low. The other path is to stop trying to cure the disease and focus entirely on keeping the patient comfortable, managing pain, and helping them live their remaining time with as much ease and dignity as possible. This second approach is known as best supportive care. It is not about giving up; it is about actively treating symptoms like pain, nausea, or trouble breathing, and providing emotional support. The question that haunts many families and doctors is whether pushing forward with more cancer drugs offers any real benefit, or if it only adds side effects and stress without extending life.

A new study called the TRUE trial is designed to answer this question directly. The researchers are not testing a specific new drug or a single treatment plan. Instead, they are comparing two different ways of thinking about care for patients who have run out of standard options. One group of patients receives the cancer drugs their doctors choose, while the other group receives the best supportive care described above. The goal is to see which approach leads to a longer life and a better quality of life. The study involves 300 patients across 46 hospitals in Japan, and it is currently recruiting. By following these patients closely, the researchers hope to provide clear evidence that can help doctors and families make the hardest decisions with more confidence.

The study focuses on patients with solid tumors, such as cancers of the lung, stomach, breast, or colon, that have reached an advanced stage. These patients have already tried the treatments that medical guidelines recommend, and their doctors feel that no further standard therapy is strongly advised. Despite this, in everyday practice, many doctors still prescribe additional drugs, sometimes out of hope or because the patient wants to try everything possible. This situation is often called "desperation oncology," where treatment continues even when the evidence for its success is very weak. The TRUE trial seeks to find out if this extra effort actually helps. The researchers are not comparing treatment against doing nothing. The control group receives active, specialized care that addresses symptoms and supports the patient, which is a vital part of medicine in its own right.

The trial is set up as a randomized study, meaning patients are assigned by chance to one of two groups. One group gets the physician's choice of systemic anticancer therapy, which means the doctor picks a drug or combination of drugs they believe might help, following the rules of the country's health insurance system. The other group receives best supportive care for a specific period of twelve weeks. During this time, they do not receive any cancer-fighting drugs, but they do get all the necessary support for their symptoms, including pain management, oxygen if needed, and procedures to relieve blockages or fluid buildup. After those twelve weeks, the doctors in the control group are free to start cancer drugs if they feel it is necessary. This design allows the study to compare the two strategies fairly while still respecting the reality that a patient's condition can change quickly.

The main thing the researchers are measuring is how long the patients live. They want to know if the group receiving the extra cancer drugs lives longer than the group receiving only supportive care. However, they know that living longer is not the only thing that matters. A treatment that adds a few months to life but leaves the patient feeling terrible might not be worth it. So, the study also looks at how the patients feel every day. They use surveys to ask about pain, energy levels, and overall well-being. They also track how often patients need to go to the hospital or the emergency room, and how many days they spend in the hospital. This gives a full picture of the burden of treatment versus the benefit.

The researchers are careful to make sure the study reflects real life. They do not force doctors to use a specific drug or follow a rigid schedule. Instead, they let the doctors treat the patients as they normally would, which makes the results more useful for everyday practice. The study is large enough to detect a meaningful difference if one exists. The researchers estimate that if the best supportive care group lives for an average of six months, they are looking to see if the treatment group can extend that to nine months. They have planned to enroll 300 patients to ensure they have enough information to draw a solid conclusion.

This approach is different from many other cancer studies that test a single new drug against a standard one. Here, the comparison is between two different philosophies of care. One philosophy prioritizes trying to fight the cancer with more drugs, while the other prioritizes comfort and quality of life first. The study acknowledges that some patients might still respond to the drugs, and that is why the control group is allowed to start treatment after twelve weeks. This flexibility makes the study more ethical and practical, as it does not deny patients the possibility of treatment forever.

The results of this trial are expected to be very important for shared decision-making. When a doctor and a patient sit down to discuss the next steps, they often have to guess whether the extra treatment will help or hurt. This study aims to replace that guesswork with facts. If the data shows that the extra drugs do not extend life or improve how patients feel, it will give doctors and families the confidence to focus on comfort care without feeling like they are missing out on a cure. If the data shows that the drugs do help, it will provide a clear reason to continue them.

The study is being conducted by a team of experts from many different hospitals across Japan, from the north to the south. It is supported by the National Institute of Public Health, which ensures that the research is conducted with high standards. The findings will be shared with the medical community and the public once the study is complete. Until then, the trial continues to enroll patients, gathering the data needed to answer one of the most difficult questions in modern medicine: how best to care for people when the cure is no longer possible. The hope is that this work will bring clarity to a confusing and emotional time, helping everyone involved to make choices that truly support the patient's well-being.