Research into cancer of unknown primary

Researchers around the world are looking at better ways to monitor and treat cancer of unknown primary (CUP). Go to Cancer Research UK’s clinical trials database if you are looking for a trial for CUP in the UK. You need to talk to your specialist if there are any trials that you think you might be able to take part in.

Some of the trials on this page have now stopped recruiting people. It takes time before the results are available. This is because the trial team follow the patients for a period of time and collect and analyse the results. We have included this ongoing research to give examples of the type of research being carried out in CUP. 

Research and clinical trials

All cancer treatments must be fully researched before they can be used for everyone. This is so we can be sure that:

• they work
• they work better than the treatments already available
• they are safe

Research into the diagnosis

Knowing where the cancer started (the primary tumour) helps doctors plan the treatment. So, researchers are looking at how cancer tests can improve the diagnosis of CUP.  

Doctors can often tell where a cancer started by looking at the cancer cells under a microscope. These doctors are called pathologists. But sometimes this does not give enough information. So, they may use other techniques such as:

• immunohistochemistry (IHC)
• genetic and molecular profiling

Immunohistochemistry (IHC)

IHC is a way of staining tissue to find proteins (antigens). It can sometimes tell what type of cancer you have, even when other tests haven’t found out the primary cancer.

Genetic and molecular profiling

Researchers are testing techniques called gene expression profiling and molecular profiling. Both techniques look at the genes  in the secondary cancer, to try to find where the cancer started. Molecular profiling also looks at the genes in the tissue sample.

Looking at the genes or genetic profiling can also help doctors decide on treatment with new targeted cancer drugs.

Some studies have shown that genetic profiling can tell where the cancer started. This is for some not all people. Doctors want to do more research to see if having these tests improves survival for people with CUP. 

Testing tissue samples of CUP in the head and neck

Some people are diagnosed with squamous cell carcinoma (SCC) that has spread to the lymph glands in the neck. But it is not known where the primary cancer started. So, it is classed as a cancer of unknown primary (CUP) of the head and neck.

Researchers are hoping a new way of testing tissue samples might help work out where the primary cancer started.

Squamous cell carcinoma (SCC) is a cancer that starts from the cells lining the body. One place where this cancer can start is in the oropharynx. This is the part of the throat (pharynx) behind the mouth. It includes tonsil cancer and cancer of the back part of the tongue. 

A surgical technique called tongue based mucosectomy (TBM) can remove this tissue to see if the primary cancer is in it.

This trial will use the TBM samples and carry out a new testing method on them. This looks at the tissue in more detail. The researchers hope this will be better at finding the primary tumour.

Research into treatment

There are some clinical trials looking at treatment for CUP. Researchers are mainly looking at targeted cancer drugs. You may have these drugs alone or in combination.

Targeted cancer drugs

Targeted cancer drugs are one of the main treatments for some types of cancer. They work by targeting differences that a cancer cell has that helps them to survive and grow. There are many different types of targeted drugs.

Some of the targeted cancer drugs that doctors are looking at for CUP include: 

• alectinib

• vismodegib

• olaparib

• erlotinib and bevacizumab

• vemurafenib and cobimetinib

• trastuzumab

• pembrolizumab

Research into surgical techniques for CUP in the head and neck

A study is looking at a new type of robotic surgery in people who have squamous cell CUP of the head and neck. The study will focus on cancers of the mouth and throat (oropharynx).

The study will use a new robot called Versius. Versius helps surgeons perform surgery with fewer cuts (incisions). Versius has a set of robotic arms. One arm has a camera and a light on it, the other arms have surgical instruments attached to the ends. The surgeon controls the arms with hand controllers. The surgeon performs the surgery while seeing the surgical area on a screen. They put the camera and instruments through the mouth and throat to cut away the cancer.

This study aims to see how safe the Versius robot is compared to other surgical techniques. It will also record any possible side effects of the treatment and for 30 days afterwards.

Research into chemotherapy

A phase 1 trial is looking at the safety of a new drug called AVA6000 in people with CUP and other cancers. The trial team want to find out the safest dose to give to people.

AVA6000 is similar to the chemotherapy drug doxorubicin. It aims to slow or stop the cancer cells from growing. The difference with AV6000 is that it doesn’t start working until it reaches the cancer cell. This means it may have fewer side effects than doxorubicin.

Research into coping with CUP

A small study looked at the experiences of people affected by CUP. Researchers found out that people with CUP have similar issues to people with other cancer types. But they found they had them to a much greater extent.

The trial team found that many people had not heard of CUP before their diagnosis. They found it difficult to get information. And they felt anxious that some medical teams couldn’t agree on the best treatment option.

They also found that people with CUP often got referred from one medical team to another. People often lost contact with their specialist nurse as they moved between teams. This can make it more difficult for people and their families to cope.