NRG-BR009 (OFSET): Testing the Addition of Chemotherapy to the Usual Treatment of Ovarian Function Suppression Plus Hormonal Therapy in Premenopausal ER-Positive/HER2-Negative Breast Cancer Patients Who are at High Risk of Cancer Returning

This study is for pre-menopausal women who meet the following criteria:

• Have early-stage breast cancer that is sensitive to hormones, HER2-negative, premenopausal, and have an Oncotype DX Recurrence Score® equal to or less than 25 (if they have positive axillary lymph nodes at surgery) or an Oncotype DX Recurrence Score® between 16 and 25 (if they have negative axillary lymph nodes at surgery).

The purpose of this study is to compare two commonly used treatment choices for early-stage breast cancer in premenopausal women Patients with your type of breast cancer may receive chemotherapy as part of their usual care.It is not clear with current information how much more benefit chemotherapy adds and if putting women into early menopause may give the same benefit as chemotherapy.The addition of chemotherapy to the other usual treatment could prevent your cancer from returning.

This study has two study groups.

If you are in Group 1, you will get the usual hormonal drugs to treat your type of cancer.You will get a drug as a pill you take by mouth every day.You will continue to receive the hormonal drug daily for at least 5 years unless you develop an allergy or severe side effects to the drug, or your breast cancer returns.You will be given an injection of an ovarian suppression drug.Your study doctor will talk with you about the choice of drug to be used for ovarian suppression and the injection schedule. There will be about 1980 people in this group.

If you are in Group 2, you will get the usual chemotherapy chosen by your doctor to treat your type of cancer.You also will get the usual hormonal drugs to treat your type of cancer. You will get a hormonal drug as a pill you take by mouth every day.You will continue to receive the hormonal drug daily for at least 5 years unless you develop an allergy or severe side effects to the drug, or your breast cancer returns.You will be given an injection of an ovarian suppression drug.Your study doctor will talk with you about the choice of drug to be used for ovarian suppression and the injection schedule. There will be about 1980 people in this group.

The usual approach for patients who are not in a study is treatment with surgery, radiation therapy, hormonal therapy, ovarian suppression, and sometimes chemotherapy using drugs approved by the Food and Drug Administration (FDA). For patients who get the usual approach for this cancer, about 93 out of 100 are free of cancer after 5 years.

General Risks

If you choose to take part in this study, there is a risk that using chemotherapy may or may not be better as the other usual approach of endocrine therapy with ovarian function suppression for preventing your cancer from coming back.

You also may have the following discomforts:

• Spend more time in the hospital or doctor’s office.
• Be asked sensitive or private questions about things you normally do not discuss.
• May not be able to take part in future studies.

The drugs used in this study could be very harmful to an unborn or newborn baby.There may be some risks that doctors do not yet know about.It is very important that you check with your study doctor about what types of birth control or pregnancy prevention to use during the study and for 3 months after you complete ovarian suppression and hormonal therapy and for 3 months after you complete chemotherapy.Hormonal methods of contraception may not be used.

Side Effect Risks

The study drugs used in this study may affect how different parts of your body work such as your liver, kidneys, heart, and blood. The study doctor will test your blood and let you know if changes occur that may affect your health.

There is also a risk that you could have other side effects from the study drugs.

Here are important things to know about side effects:

1. The study doctors do not know who will or will not have side effects.
2. Some side effects may go away soon, some may last a long time, and some may never go away.
3. Some side effects may make it hard for you to have children.
4. Some side effects may be mild.Other side effects may be very serious and even result in death.

You can ask your study doctor questions about side effects at any time.

There is evidence that adding chemotherapy to hormonal therapy is effective in preventing your cancer from returning.It is not possible to know if chemotherapy given with ovarian suppression and hormonal therapy will extend your time without disease compared to the ovarian suppression and hormonal therapy, a usual treatment.This study will help the study doctors learn things that may help people in the future.

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 breast cancer. This includes:

• 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 the ovarian suppression and hormonal therapy drugs, and chemotherapy if you receive chemotherapy.
• the cost of getting the ovarian suppression or chemotherapy 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 research blood samples drawn for the study.
• The Oncotype DX Recurrence Score testing if you only have a MammaPrint Low Risk or MP1 result.Genomic Health will cover the cost of the test for patients with a MammaPrint result that do not have an Oncotype DX Recurrence Score.

Taking part in this study may mean that you need to make more visits to the clinic or hospital than 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. The research may lead to new tests, drugs, or other products for sale.If it does, you will not get any payment.

Your privacy is very important to us. 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, 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 or receive copies of some of the information in 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 another group.

Some of these organizations are:

The study sponsor and any company supporting the study drug 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.
• The NCI’s National Clinical Trials Network and the groups it works with to conduct research.

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