Testing the usual treatment of radiation therapy and HER2-targeted therapy to HER2-targeted therapy alone for low-risk HER2-positive breast cancer

If you are over the age of 18 and have a grade II meningioma that has been completely removed through surgery, you may be able to participate.

This study is being done to compare any good and bad effects of using radiation to treat a meningioma that has been completely removed compared with the more common approach of observing the tumor and treating it with radiation if it returns. Researchers want to know if radiation therapy following surgery is better than observation alone.

If you decide to take part in this study, you will have surgery then you will either be observed without any radiation treatment (Group 1) or you will receive radiation therapy to the area of the brain where the meningioma was removed with careful attention to minimizing the amount of radiation received by normal tissue (Group 2).

People who are not in a study and who have had a grade II meningioma completely removed may be observed without treatment; treated with radiation following surgery; or treated with radiation therapy only if their tumor comes back. For patients who receive the common approach of observation, about 50 to 75 out of 100 are free of meningioma at three to five 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 approach may not be as good as the usual approach for your cancer. 
• The study approach 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.

It is not possible to know at this time if observing you after surgery or treating you with radiation only if the meningioma returns, is better than treating you with radiation immediately after surgery, so this study may or may not help you. This study will help researchers learn things that will help people in the future.

If you are randomized to Group 2, you will receive the radiation therapy 5 days per week for 6 1/2 to 7 weeks (33 treatments). After you finish radiation therapy, your doctor will continue to watch you for side effects and follow your condition through office visits at months 3, 6 and 12 for the first year from randomization, every 6 months for year 2 and 3, then yearly for 10 years. If you are randomized to Group 1 (post-surgery observation), your doctor will follow you through office visits at the same intervals. Patients in both Groups will have MRIs at least every 6 months from randomization for 5 years, then at least yearly for 10 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 health plan/insurance company will need to pay for all of the costs of treating and monitoring your meningioma while in this study, including the cost of tests, procedures, or medicines to manage any side effects, unless you are told that certain tests are supplied at no charge. 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.

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 
• Other organizations in the National Clinical Trials Network (NCTN): Alliance for Clinical Trials in Oncology (ALLIANCE), ECOG-ACRIN Cancer Research Group (ECOG-ACRIN), SWOG, and Imaging and Radiation Oncology Core (IROC) 
• 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 in the U.S., and similar ones if other countries are involved in the study.

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.