NRG-GI008 (CIRCULATE-NORTH AMERICA): Colon Adjuvant Chemotherapy Based on Evaluation of Residual Disease

This study is for patients who meet the following criteria:

• Have stage III colon cancer, i.e. cancer that has spread to your lymph nodes despite being treated with surgery
• Have stage IIB or IIC colon cancer that has been treated with surgery and has not spread to your lymph nodes

The  study will be seeking to determine whether chemotherapy is needed for all or
only some patients in the study population, and, if chemotherapy is needed,
what kind of chemotherapy to recommend to patients based on the presence or
absence of circulating tumor DNA (ctDNA) following surgery for colon cancer.

If you decide to take part in the study, you will be assigned to one of four study groups.

If you are ctDNA negative following surgery, you will be randomly assigned to Group 1 or 2, and if you are ctDNA positive, you will be randomly assigned to Group 3 or 4:

Groups 1 and 2 (for patients with a ctDNA-negative test)

If you are in Group 1, you will get the usual chemotherapy treatment of FOLFOX (5-FU, leucovorin, and oxaliplatin) for 3-6 months or CAPOX (capecitabine and oxaliplatin) for 3 months, as decided by your study doctor. This is the current standard of care for this disease.

If you are in Group 2, you will be monitored with ctDNA testing every 3 months through the first year, and then every 6 months for the second and third years, and you will not be treated with chemotherapy unless your ctDNA testing turns positive. Patients who develop a positive ctDNA test during monitoring will be asked to move into to one of the ctDNA-positive groups (Groups 3 or 4) with the type of chemotherapy as described below.

Groups 3 and 4 (for patients with a ctDNA-positive test at the time of enrollment or Group 2 patients who develop a positive ctDNA test)

If you are in Group 3, you will get the usual chemotherapy treatment of FOLFOX or CAPOX for 6 months, as decided by your study doctor. This is the current standard of care for this disease.

If you are in Group 4, you will get the study chemotherapy treatment of mFOLFIRINOX (5-FU, leucovorin, oxaliplatin, and irinotecan) for 6 months.

The usual approach for patients who are not in a study is treatment with chemotherapy drug combinations for colon cancer, which are 5-fluorouracil (5-FU), leucovorin, and oxaliplatin (FOLFOX), or capecitabine and oxaliplatin (CAPOX). The chemotherapy being used as part of this study is considered to be the usual approach for patients with colon cancer. For patients who get the usual approach for colon cancer, about 72 out of 100 are free of cancer after five years.

There are both risks and benefits to taking part in this study. It is important for you to think carefully about these as you make your decision. If you choose to take part in this study, there is a risk that:

• You may lose time at work or home and spend more time in the hospital or doctor’s office than usual.
• You may be asked sensitive or private questions which you normally do not discuss.
• You may be exposing yourself to the potential risks associated with ctDNA testing.
• If you choose to take part in this study and ctDNA is not found in your blood at the time of enrollment, there is a risk that the approach of ctDNA testing every 3 months and either not receiving or delaying chemotherapy may not be as good as the usual approach for your cancer.
• If you choose to take part in this study and ctDNA is found in your blood, there is a risk that the mFOLFIRINOX chemotherapy treatment may not be as good as the FOLFOX or CAPOX for your cancer.
• There is also a risk that you could have side effects from the mFOLFIRINOX chemotherapy treatment. These side effects may be worse and may be different than you would get with the usual chemotherapy treatment for your cancer.

Some of the most common side effects that study doctors know about are:

• Numbness, tingling or pain, “pins and needles” in the hands, feet, arms, and legs
• Tingling or a loss of feeling in your hands, feet, nose, or tightness in throat or jaw, or difficulty swallowing or breathing, which may be made worse by exposure to cold
• Infection, especially when white blood cell count is low
• Nausea, vomiting, and diarrhea
• Hair loss
• Sores in mouth which may cause difficulty swallowing
• Hand-foot syndrome (palmar-plantar erythrodysesthesia) redness, pain, or peeling of palms and soles
• Anemia
• Pain
• Loss of appetite

Your doctor will review all of the potential side effects with you, though there may be some risks that the study doctors do not yet know about. It is important to tell your doctor about any side effects as soon as possible during the study so that they can be addressed and so that potential adjustments to your treatment can be made.

There is some  evidence that the presence of ctDNA in patients after their surgery may mean
that there is a higher risk of their cancer returning. Only giving chemotherapy  to patients who develop a positive ctDNA test could potentially allow some
patients—ctDNA-negative patients—to avoid unnecessary chemotherapy. It is not  possible to know now if using chemotherapy based on results of ctDNA blood
testing will be better at extending your time without your cancer returning  compared to the usual approach. This study will give the study doctors
information that may help cancer patients in the future.

After you finish your treatment, your doctor and study team will continue to watch you for side effects, checking every 3-6 months for a total of five years. These checks will be completed during visits to your study doctor.

If you are ctDNA negative and do not develop a positive ctDNA test, you will receive regular check-ups every 3-6 months for a total of five years after you join the study without further treatment for your colon cancer.

If you are ctDNA negative and develop a positive ctDNA test during monitoring and agree to change to the ctDNA-positive group or have a positive ctDNA test at study entry (Group 3 or Group 4) and receive study treatment, your doctor and study team will watch you for side effects after you finish your treatment, checking every 6 months for four and a half years after treatment.

It is possible that you could be on this study for up to eight years.

No. Taking part in this study is voluntary. You are free to choose to participate or not to participate. If you choose to participate in this study, you are able to leave the study at any time. If you decide not to take part in this study, your doctor will discuss other treatment options with you.

You and/or your insurance plan will need to pay for the costs of medical care you get as part of the study, just as you would if you were getting the usual care for your colon cancer. This includes:

• the costs of the ctDNA testing done using the Signatera assay, if done as part of your usual care for your colon cancer
• the cost of tests, exams, procedures, and drugs that you get during the study to monitor your safety and prevent and treat side effects
• the cost of getting FOLFOX, CAPOX, or mFOLFIRINOX ready and giving it to you
• your insurance co-pays and deductibles

Talk to your insurance provider and make sure that you understand what your insurance pays for and what it doesn’t pay for if you take part in this clinical trial. Also, find out if you need approval from your plan before you can take part in the study.

Ask your doctor or nurse for help finding the right person to talk to if you are unsure which costs will be billed to you or your insurance provider.

You and/or your insurance provider will not have to pay for exams, tests, and procedures done for research purposes only or that are covered by the study. These include:

• the ctDNA blood tests done while you are on the study.

Taking part in this study may mean that you need to make more visits to the clinic or hospital than you would if you were getting the usual approach to treat your cancer. You may:

• Have more travel costs
• Need to take more time off work
• Have other additional personal costs

You will not be paid for taking part in this study, nor will you be paid if the research leads to new tests, drugs, or other products for sale.

Your privacy is very important to us and the researchers will make every effort to protect it. Your information may be given out if required by law. For example, certain states require doctors to report to health boards if they find a disease like tuberculosis. However, the researchers will do their best to make sure that any information that is released will not identify you. Some of your health information and/or information about your specimens from this study will be kept in a central database for research. Your name or contact information will not be put in the database.

There are organizations that may inspect your records. These organizations are required to make sure your information is kept private, unless required by law to provide information. Some of these organizations are:

• NRG Oncology and Janssen, the company supporting the study now or in the future. This would include any organization helping the company with the study.
• The NCI Central IRB, which is a group of people who review the research with the goal of protecting the people who take part in the study.
• The FDA and the groups it works with to review research.
• The NCI and the groups it works with to review research, including the Cancer Trials Support Unit (CTSU).
• The NCI’s National Clinical Trials Network and the groups it works with to conduct research including the Imaging and Radiation Oncology Core (IROC).

Doctors and researchers conduct a clinical study, also called a “clinical trial,” to find better ways to prevent, diagnose, or treat an illness. NRG Oncology is supported by the National Cancer Institute (NCI) and runs clinical studies specifically for patients with cancer or to prevent cancer. Most clinical studies test something we know against something we don’t know. In all situations, these studies are strictly evaluated before they are allowed to be offered to any patient. The study is designed to answer the question that we do not know the answer to, so that current and future patients may have better treatments or information than what we currently have. There are different types of clinical studies that might be available for patients. For more information see “Types of Clinical Trials” and “Phases of Clinical Trials”.

Patients who volunteer to take part in a clinical study are followed closely by their health care professionals and members of the research team. For more information see “Research Team Members”.

Yes. They are exactly the same thing.

The care cancer doctors provide to cancer patients today is the direct result of clinical studies (also known as clinical trials) that were done in the past. Clinical studies give doctors and the treatment team information about what types of treatments work and what treatments do not work, in a number of different situations. Some studies focus on treating the cancer, others on preventing the cancer, and others on helping patients feel better or healthier during or after treatments. When you take part in a clinical study, you add to our knowledge about cancer and it may help improve cancer care for future patients. Clinical studies are available to patients with many types of cancer and at all stages of treatment. In some situations, the only way to get these new treatments is by joining a clinical study.

A clinical study may take place in many locations, such as:

A study is typically led by a principal investigator who is a doctor or other advanced health care professional. A clinical study is carried out by following a very specific plan known as the “protocol”. The protocol is designed so all patients in the study are treated as well as possible and in the same way. The protocol also provides rules for the doctors and clinical study staff to follow to keep patients safe and make sure the study is run in an ethical manner.

No, not at all. Participation in a clinical study is completely voluntary. For more information see “Deciding to Take Part in a Clinical Trial”. You are free to choose to participate or not to participate. If you choose to participate in a study, you may still decide to leave the study at any time. If you decide not to participate in a study, your doctor will discuss other treatment options with you. For more information see “Questions to Ask Your Doctor about Treatment Clinical Trials“.

• You may choose to have the usual treatment approach (known as “standard of care”)
• You may choose to take part or learn more about a different study, if one is available
• You may choose not to be treated for cancer