The COBRA Study: Circulating Tumor DNA Testing in Predicting Treatment for Patients With Stage IIA Colon Cancer After Surgery

This study is for men and women who have early-stage (Stage IIA) colon cancer that has been treated with surgery and for whom close monitoring, but not chemotherapy, would otherwise be recommended by their treating doctor.

We want to find out if testing for ctDNA in patients who have early-stage colon cancer that has been treated with surgery alone and offering additional chemotherapy for those who test “positive” is better or worse than the usual approach of close monitoring for all patients without chemotherapy after surgery. We are also doing this study to see if the ctDNA test can identify patients with colon cancer after surgery who do benefit from receiving chemotherapy.The usual approach for most people with early-stage colon cancer is surgery alone.

The COBRA Study has 2 groups. If you participate, you would be assigned to only one of these two groups, based on randomization – a process through which you have equal chance of being in one or the other group, but based completely on chance.

If you are in the first group, your treatment will be the same as it would be if you were not in the study, surgery only with close follow-up. You will receive regular check-ups with your doctor after you join the study, but no further treatments will be given to you for your colon cancer.You will have blood collected at different time points when you would be in the doctor’s office anyway, and your blood samples will be stored and tested in the future for ctDNA.

If you are in the second group, your blood will be tested at the beginning of the study, and your treatment will be determined by whether or not ctDNA is found in your blood. If ctDNA is found in your blood, you will receive chemotherapy for about 6 months after joining the study. The treatment will be one of the usual chemotherapy regimens for colon cancer: 5-fluorouracil (5-FU), leucovorin, and oxaliplatin (mFOLFOX6); or capecitabine and oxaliplatin (CAPOX). Your doctor will decide which of these regimens you receive. If ctDNA is not detected in your blood, you will receive regular check-ups with your doctor after you join the study, but will not receive any further treatment after surgery for your colon cancer, similar to if you were not in the study.

The usual approach for patients with your cancer is no further treatment after surgery.All patients entering this study are considered to be at low risk for their cancer returning based on the usual tests and scans done at the time their cancer is diagnosed and the testing done on their tumor after it is removed during surgery.So, close follow-up is all that is recommended.

In the past, testing for ctDNA was not offered to patients in this situation, but commercially available test(s) for ctDNA are now available outside of this study.A ctDNA test may help doctors determine a patient’s risk for having their cancer return.However, the use of ctDNA testing is not currently considered to be a standard of care, because it is not known whether ctDNA could identify patients that may benefit from chemotherapy.At this time, there is no test (including ctDNA testing) that exists that helps doctors identify with certainty which patients with early-stage colon cancer will or will not benefit from chemotherapy.Doctors have previously looked into other methods that might determine which cancers have a high risk of returning, but none of those other methods have been able to show for certain whether or not chemotherapy should be recommended.

The chemotherapy that may be recommended as part of this study is considered to be the usual approach for patients with a high risk for their colon cancer returning.

For patients who receive the usual approach for low-risk colon cancer, on average, about 90 out of 100 are free of cancer after five years.

• Spending more time than you would otherwise in the hospital or doctor’s office.

• Being asked sensitive or private questions about things you normally do not discuss.

• If you choose to take part in this study, your blood is tested for ctDNA at the beginning of the study, and if ctDNA is detected in your blood, then you may receive chemotherapy earlier than you otherwise would if your cancer were to be detected through more commonly used tests like CT scans.

• If you choose to take part in this study and your blood is not tested for ctDNA at the beginning of the study, you and your doctor will not know the status of your ctDNA, and you will receive the usual approach of no treatment and ongoing close follow-up with standard CT scans.Your doctor would start chemotherapy only if the cancer returned.It is not known at the present time if there is a benefit from early treatment with chemotherapy; that is an important question being addressed by this study.

• There is also a risk that you could experience side effects from the chemotherapy.These side effects may be worse and may be different than you would get with the usual approach for your cancer. Your doctor will review all of the possible side effects with you if chemotherapy is part of your treatment as part of this study. It is important to tell your doctor about any side effects that you experience during the study so that they can be addressed and so that potential adjustments can be made.

There is some evidence that the presence of ctDNA in patients after their surgery may mean there is a higher risk of their cancer returning. It is not possible to know now whether giving chemotherapy based on results of ctDNA blood testing or the usual approach of no further treatment will be better. Having a reliable test that could predict which patients should receive treatment to keep their cancer from returning would be helpful. This study will, enable study doctors to learn things that may help people in the future.

Patients will be followed for 3 years after joining the study.

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.These costs include:

• the costs of the tests, exams, procedures, and drugs that you get during the study to monitor your safety and to prevent and treat side effects.

• the cost of getting 5-fluorouracil, leucovorin, oxaliplatin [mFOLFOX6] or capecitabine and oxaliplatin [CAPOX]) and the cost of getting mFOLFOX6 and CAPOX 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 will pay for and what it won’t pay for if you take part in this clinical trial.Also find out if you need approval from your insurance 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 and which will be covered by your insurance provider.

Your privacy is very important to us, and the study doctors will make every effort to protect it.The study doctors have a privacy permit to help protect your records if there is a court case.However, some of your medical information may be given out if required by law.If this should happen, the study doctors will do their best to make sure that any information that goes out to others will not identify who you are.

Some of your health information, such as your response to cancer treatment, the results of study tests, and medicines you took, will be kept by the study sponsor in a central research database.However, your name and contact information will not be put in the database.If information from this study is published or presented at scientific meetings, your name and other personal information will not be used.

There are organizations that may look at your study records.Your health information in the research database also may be shared with these organizations.They must keep your information private, unless required by law to give it to provide information.

Some of these organizations are:

• NRG Oncology and any company supporting the study now or in the future.

• The National Cancer Institute (NCI) Central Institutional Review Board (CIRB), which is a group of people who review the research with the goal of protecting the people who take part in the study.

• The Food and Drug Administration (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 (NCTN) and the groups it works with to conduct research.

• Guardant Health, the Laboratory that will test for ctDNA. The laboratory will receive identifiable information from your pathology report that is sent with your tumor tissue.Your identifiable information will only be used for the purposes of the study and will be kept private.It will only be shared with the members of the study team.

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:

physician offices

hospitals

clinics

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