Colon or rectal cancer spread to the liver

Introduction.

Do you have colon or rectal cancer that has spread to your liver? Doctors often call this ‘metastatic colorectal cancer to the liver’.

If you have the disease – and the cancer in your liver is currently untreatable with surgery - you may be able to join this medical research study.

That’s provided at least 80% of all the cancer in your body (excluding your colon or rectum) is located in your liver. And you haven’t started chemotherapy yet.

Study purpose

The study’s purpose is to test the effectiveness of a ‘study device’ when used in combination with standard chemotherapy. It’s hoped this combination might help kill liver tumors in people with your condition better than standard chemotherapy alone.

Why is it called a ‘study device’? Because it hasn’t been approved by the Food and Drug Administration (FDA) as a treatment for metastatic colorectal cancer to the liver.

The study device consists of thousands of tiny round beads (about the diameter of the human hair) called LC beads. These contain a chemotherapy drug called irinotecan that is used in the treatment of metastatic colorectal cancer. 

Half of the 60 people who participate in this trial will be chosen at random to have the LC beads inserted in their liver in combination with standard chemotherapy. This random selection process will be done in a way that’s similar to flipping a coin. The people who don’t receive the LC beads will receive standard chemotherapy alone.

This standard chemotherapy is called FOLFOX. It is the first treatment given to almost everyone diagnosed with your disease. All study participants will also be able to receive the cancer-fighting drug, Avastin.

These standard treatments will be managed and delivered by your existing Medical Oncologist. Importantly, your Medical Oncologist will be kept fully informed about the study-related procedures that you undergo. And how you respond to them.

The study is open to people across the United States. However, if you join and are then chosen to receive the LC beads, you’ll need to make up to 3 or 4 visits to one of the participating hospitals or medical research centers. These are located in cities around the country.

How the study device works

Before describing how the study device works, it’s worth explaining how people with your condition are usually treated when first diagnosed. Known as the ‘standard of care’, the treatment involves the chemotherapy drug FOLFOX mentioned above.

FOLFOX is given via an intravenous drip. Because it’s then allowed to travel through the entire body, the treatment is called ‘systemic’ chemotherapy.

FOLFOX systemic chemotherapy often gets good results. However, it tends to be less effective in cases where 80% or more of all the cancer in a person’s body lies within their liver.

One way doctors can deal with this problem is to combine FOLFOX with the chemotherapy drug, irinotecan. However, if the irinotecan is allowed to travel with FOLFOX through the whole body, most patients will experience severe side effects.

The study’s research team believes these severe side effects can be minimized by restricting the irinotecan’s movement to the tumours in your liver and the area immediately around them.

To do this, the irinotecan must be delivered directly to the tumors rather than being given to your whole body. Delivering the drug in this targeted way is the role of the irinotecan-loaded LC beads in this study.

Doctors call this targeted delivery of a chemotherapy drug ‘chemoembolization’ or ‘TACE’ (Trans Arterial Chemo Embolization).

The bead procedure explained

If you join this study and are selected to receive the beads, they’ll be inserted into the blood vessels in your liver that feed your tumor. This is called a ‘minimally invasive’ procedure as it’s done through a blood vessel in the groin and does not involve open surgery.

Once in place, the beads will act in two ways. Firstly, they will stop blood flowing to your tumor. Researchers hope that this blockage may help to kill it. Secondly, the beads will release the irinotecan directly into your tumor. It’s hoped this will further assist in your tumour’s death.

As mentioned earlier, researchers expect the irinotecan to be contained within your tumor and the area immediately around it. If this targeted approach works, there will be two benefits.

First of all, it will stop the irinotecan harming healthy liver tissue and other areas of your body. That may mean fewer irinotecan-related side effects like hair falling out. In turn, this will allow stronger doses of irinotecan to be given than is possible when given to the whole body.

LC bead and irinotecan approved for other uses

As mentioned earlier, the study device doesn’t have FDA approval as a treatment for metastatic colorectal cancer to the liver. However, the LC beads - without irinotecan - are approved as a means of blocking blood vessels that supply blood to tumours in the liver.

Meanwhile, irinotecan – without LC beads – is approved by the FDA as a treatment for metastatic colorectal cancer to the liver.

You can leave at any time

Participation in this study is voluntary. That means you’re free to withdraw without having to give a reason. Doing so will not affect your standard medical treatment for metastatic colorectal cancer to the liver in any way.

What participation entails.

If this clinical trial interests you, it’s important you understand what’s involved before deciding to join. To build this understanding, you’ll obviously need to discuss the trial with the healthcare professionals who’re running it. And ideally with your Medical Oncologist, friends and family.

Your first conversation with the clinical trial team will be on the phone. Then, if you and they wish to continue the discussion, you’ll attend a face-to-face meeting. This will be with the physician running the clinical trial. Also at the meeting will be the Research Coordinator. This person manages the clinical trial on a day-to-day basis.

These conversations will allow you to fully understand how the trial works. And they’ll allow the research team to find out whether you might be eligible to participate.

The Informed Consent Document

If, after these conversations, you’re still interested in joining, you’ll be invited to read a so-called ‘Informed Consent Document’. This explains the study in detail. And it’s written in a style that’s easy to understand.

Once you’ve understood the Informed Consent Document, you must sign it if you still wish to participate. If you do this, you’ll move to the next stage, known as ‘screening’.

How you’ll be screened

The screening process involves tests to check whether you’re eligible to join the clinical trial. And whether you’re healthy enough to participate.

These include blood tests and a CT scan to measure your tumors.

If you pass the screening tests, you’ll be enrolled in the clinical trial. And if you’re one of the 50% of study volunteers randomly selected to receive the LC beads, you’ll have your first injection one week after your Medical Oncologist gives you your first FOLFOX chemotherapy treatment.

The bead injection procedure

The procedure to inject the LC beads is minimally invasive. In fact, you remain awake throughout. At the start of the procedure, you’ll be given pain medication and sedatives.

Next, a small flexible tube will be inserted into the artery in your groin. This tube is called a catheter and is about the size of a piece of spaghetti.

The catheter will be guided towards the blood vessels in your liver that feed your tumor. This is done using X-ray equipment. Once the catheter is in place, the LC beads are injected through it and out into the target blood vessels.

After the procedure, you’ll stay in hospital for observation for up to 23 hours.

About two weeks after receiving your first injection of beads, you’ll receive another. If only one side of the liver has cancer, the beads will be injected into that area again. Meanwhile, where both left and right halves have cancer, the next bead injection will be into the opposite side. The procedure is the same.

In total, you’ll receive two to three injections into each affected area of the liver. Therefore, you could have up to six injections if you have tumors throughout the liver.

Your standard treatment continues

In the weeks when you’re not receiving the beads, you’ll receive your standard FOLFOX chemotherapy treatment. As mentioned earlier, this will be managed and delivered by your existing Medical Oncologist.

Meanwhile, you’ll undergo medical tests throughout the trial. These will include CT scans, blood tests and evaluations of your vital signs. The tests will reveal how your body is responding to the combination of FOLFOX systemic chemotherapy and LC beads loaded with irinotecan. And show whether you’re healthy enough to stay in the clinical trial.

What happens once all your bead injections are complete? You’ll be monitored in the study for a further two years.

Meanwhile, the beads don’t need to be taken out. As a result, they’ll stay in your body permanently.

Potential risks.

What risks might you face by participating in this study? First of all, it’s possible the colon or rectal cancer that has spread to your liver may not get better.

Also, there are a variety of other risks you need to consider before deciding to participate. Each of these will be explained to you by the research team. They’re also explained in the Informed Consent Document.

Side effects are amongst the things you’re most likely to experience. These could arise from your standard FOLFOX chemotherapy and/or the LC beads containing irinotecan.

Using FOLFOX and irinotecan-loaded LC beads together may increase the chance of side effects compared to when they’re used separately. However, any side effects would probably be the same as those that occur when each is used alone.

So which side effects do you have a 50% chance or greater of experiencing?

Firstly, FOLFOX chemotherapy can be associated with unwanted symptoms like:

• Mouth sores
• Poor appetite
• Taste changes, metallic taste in mouth during infusion
• Discoloration along the vein through which the medication is given
• Low blood counts.  Your white and red blood cells and platelets may temporarily decrease.  This can put you at increased risk for infection, anemia and/or bleeding.
• Peripheral neuropathy – numbness and tingling and cramping of the hands or feet often triggered by cold.
• Fatigue
• Loss of appetite
• Non-life threatening allergic reaction – rash, itching, facial flushing.

Many of these are managed using other medications.    

Besides side effects, the trial also involves procedures that give rise to a variety of risks. For example, you might experience pain where the catheter is inserted. And the blood draws may cause you some discomfort.

There are also risks associated with some of the technologies used in the study. For example, x-rays and CT scans.

While the above are known risks, there may also be risks that are unknown or unforeseeable.

Potential benefits.

If you choose to join this study, there is the potential for several benefits to arise.

Firstly, if you receive standard FOLFOX chemotherapy and the study device, your tumor or tumors might shrink more than in people who only receive standard FOLFOX chemotherapy. If so, this may prolong your survival. However, this is not certain.

Secondly, by joining this study, you will help medical researchers find a better treatment for colon and rectal cancer that has spread to the liver.

Costs of participation.

If you’re interested in joining this study, you need to understand the financial consequences of doing so.

For a start, you and your insurance company will be billed for all of the standard of care (i.e. routine) costs of treating you in the study.

Examples include doctor’s office visits, blood tests, x-rays, CT scans and EKGs that would be done even if you weren’t participating in the trial.

You will be responsible for paying your co-pay that is associated with any procedures.

None of the charges from the doctor’s office or hospital during your participation in this study will be paid for by the research program.

Importantly, some insurance companies won’t cover routine treatment costs for people who participate in a research study. Therefore, you must ask your insurance company what they will pay before participating in this clinical trial. If needed, a study staff member may be able to help you do this.

If your insurance company won’t pay your study-related bills, you’ll have to pay them yourself.

Meanwhile, you won’t be billed for the tests and procedures that are only done for this clinical trial. In other words, those that wouldn’t be necessary if you were not taking part.

Finally, please note that if you’re injured by the research, you may incur extra costs.