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

If you are over the age of 18 with advanced-stage prostate cancer that has returned and spread with a limited number of metastases (up to 5 lesions) following treatment and you are NOT currently receiving androgen deprivation therapy, you may be able to participate

This study is being done to determine if we can lower the chance of your prostate cancer growing or spreading by adding the drug relugolix to the usual radiation therapy.

We are doing this study because we want to find out if this approach is better or worse than the usual approach for your prostate cancer. The usual approach is defined as care most people get for prostate cancer.

If you decide to take part in the study, you get randomly assigned to one of two possible treatments.
Trial participants who are assigned to Treatment Group 1 will receive a placebo with high dose stereotactic ablative body radiation (SABR) to the sites of their metastasis. Trial participants who are assigned to Treatment Group 2 will receive the study drug relugolix with SABR to the sites of their metastasis. However, you and your doctor will not know which group you will be in.

People who are not in a study are usually treated with hormonal therapy or radiation therapy to help treat their cancer. In prostate cancer that has spread to only a few areas, the usual treatment either involves short term hormone therapy or radiation therapy to the sites of metastasis to delay hormone therapy. Radiation therapy directed at the sites of metastasis is a very focused high dose of radiation used to control the cancer (called stereotactic ablative body radiotherapy, or SABR). Sometimes a lower dose of radiation is used at the sites of metastasis for symptom relief only. For patients who undergo the high dose radiation alone, about 66 out of 100 start hormonal therapy within 5 years.

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.
• The study drugs may not be as good as the usual approach for your cancer at shrinking or stabilizing your cancer and preventing your cancer from spreading.
• The drugs used on this trial may cause side effects. Your doctor will review all of the potential side effects with you. It is important to tell your doctor about any side effects during the study so that they may be treated and so that potential adjustments to the study drugs may be made.

There is evidence that adding the study drug, relugolix, is effective in stabilizing your type of cancer. It is not possible to know now if the study drug will extend your time without disease spreading compared to the usual approach. This study will help the study doctors learn things that will help people in the future.

Both groups will receive the drug or placebo for 6 months and the SABR treatment for 1-3 weeks.

After you finish your study treatment, your doctor will continue to follow your condition and watch you for side effects. They will check at 3 and 6 months after you finish treatment, then every 6 months for 4 years, and then yearly.

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 cancer.
This includes:

• the costs of tests, exams, procedures, and drugs that you get during the study to monitor your safety and prevent and treat side effects. 
• the costs of getting the study drug, relugolix, or placebo ready and giving it to you. 
• the costs of the radiation therapy 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. 

You or your insurance provider will not have to pay for the study drug, relugolix, or placebo while you take part in this study. 

You will not be paid for taking part in this study.

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, Myovant Sciences GmbH, Pfizer Oncology, or the companies supporting the study now or in the future. This would include any organization helping the company with the study. 
• The National Cancer Institute (NCI) Central Institutional Review Board, 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 and the groups it works with to conduct research including the Imaging and Radiation Oncology Core (IROC).

Men or women may be able to participate if they have colorectal cancer that is known to have a specific alteration that may or may not be hereditary (MSI-high/DNA mismatch repair deficient), has spread to other parts of their body (metastatic), and they have not yet received treatment for their metastatic colorectal cancer. Your healthcare team is the best source for information about your treatment options, including cancer clinical trials. Be sure to take this information to your doctor to discuss your questions and concerns in general and specific to this trial.

Immunotherapy is a standard first-line treatment for MSI-high/DNA mismatch repair deficient metastatic colorectal cancer.

This study is trying to answer the question of whether adding chemotherapy FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) and bevacizumab (biologic therapy routinely added to FOLFOX) to immunotherapy (atezolizumab) treatment improves efficacy compared to atezolizumab alone.

Patients in this study will be randomly assigned to receive one of these two treatment options.

All patients will be randomly assigned to one of two groups in the study. Group 2 will receive immunotherapy alone with atezolizumab. Group 3 will receive the same immunotherapy with FOLFOX and bevacizumab. The type of chemotherapy you will receive is a combination called FOLFOX which includes 5-fluorouracil (5-FU), leucovorin, and oxaliplatin. Bevacizumab, a biologic therapy, is routinely added to FOLFOX. NOTE: there was previously a Group 1 in this study who did receive FOLFOX and bevacizumab chemotherapy and no atezolizumab. This treatment group is no longer an option.

Patients with metastatic colorectal cancer which is MSI-high/DNA repair deficient who are not in a research study are usually treated with immunotherapy. The Food and Drug Administration (FDA)-approved immunotherapy with pembrolizumab for the first-line treatment of patients with unresectable or metastatic MSI-high/DNA mismatch repair deficient colorectal cancer

• 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.
• There is a risk someone could get access to the personal information in your medical records or other information researchers have kept about you.  Someone might be able to trace this information back to you.  The researchers believe the chance that someone will identify you is very small, but the risk may change in the future as people come up with new ways of tracing information. In some cases, this information could be used to make it harder for you to get or keep a job.  
• Adding FOLFOX and bevacizumab to atezolizumab for this type of cancer may not be better than atezolizumab alone, and could possibly be worse, than the standard immunotherapy alone for your cancer.  

It is not possible to know if adding chemotherapy and biologic treatment to the standard immunotherapy treatment is better than immunotherapy alone, so this study may or may not help you.  However, all of these treatments are commonly used for patients with this disease.  This study will help researchers learn things that may help future patients with this type of cancer.

You will receive atezolizumab (Group 2) or atezolizumab with 5-FU, leucovorin, oxaliplatin and bevacizumab (Group 3). If you are in Group 3, for as long as you continue to benefit or as long as your doctors think it is safe to keep you on therapy, you will continue on treatment with 5-FU, leucovorin, and bevacizumab. Oxaliplatin will continue up to a total of 10 cycles in this group. 

In either group, you will receive atezolizumab for up to 2 years. 

If you stop study treatment for any reason, your study doctor will see you about 1 month after you stop to check for any side effects that you may be having. If your cancer has not progressed (grown) at the time you stop study treatment, you will continue to have scans until your cancer grows or until you begin another treatment for your cancer.  After that, the researchers who are conducting this study would like to know how you are doing about every 6 months from the time you stop study therapy through about 5 years from when you joined the study.  This can be done at a visit to your study doctor or by a phone call from your study team.

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.

Atezolizumab will be supplied at no charge while you take part in this study.  It is possible that atezolizumab may not continue to be supplied while you are on the study. Although not likely, if this occurs, your study doctor will talk to you about your options.

Neither you nor your health care plan/insurance carrier will be billed for the collection and shipping of blood or tumor samples associated with this study. 

You and/or your health plan/insurance company will need to pay for all of the other costs of treating your cancer while in this study, including the cost of the other standard treatment drugs, 5-fluorouracil, leucovorin, oxaliplatin, and bevacizumab and the cost of getting the IV drugs ready and giving them to you, the cost of tests and procedures, and the cost of managing any side effects. Before you decide to be in the study, you should check with your health plan or insurance company to find out exactly what they will pay for. 

You will not be paid for taking part in this study.

• The study sponsors, NRG Oncology and SWOG, and Genentech or any other drug company supporting the study
• Alliance for Clinical Trials in Oncology and ECOG-ACRIN Cancer Research Group
• The Institutional Review Board, IRB, 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 and the National Cancer Institute (and its agents) in the U.S.