I-SPY 2 TRIAL: Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging And MoLecular Analysis

About the Trial

The I-SPY 2 TRIAL is enrolling women with newly diagnosed invasive breast cancer. If your tumor is 2.5 cm or larger in size, you are eligible to be screened for this study. The purpose of the screening phase of this study is to find out more about your cancer and if you are eligible to participate in the treatment phase of this study.

My Participation in I-SPY 2 »
I-SPY 2 Study Procedures »

My Participation in I-SPY 2

Screening Phase

A study doctor and study coordinator will discuss the trial with you and give you a screening consent form that explains the screening study procedures and tests (also shown in diagram below).

The screening phase includes taking some tissue from your tumor to do some tests to find out more about your cancer. The tissue can be collected either at the time of your diagnostic core biopsy or if you have already had a diagnostic core biopsy, you will have another core biopsy prior to your treatment for the purposes of this study.

You will also have an MRI scan of your breasts and a blood draw to find out more about your cancer. All of these procedures and test will be done to find out if you are eligible to join the treatment phase of this study.

To determine if you are eligible for the treatment phase of this study, the study will use common biomarkers used in breast cancer. These include: Estrogen Receptor (ER) status, Progesterone Receptor (PR) status, Her2 receptor status. The study will also use TargetPrint Her2 and MammaPrint risk score, which are approved research tests. TargetPrint Her2 is another test of the Her2 receptor that looks at the amount of these genes in your tumor. MammaPrint is a test to find out if your cancer is at high risk for recurrence if you did not have any treatment, other than surgery, for your cancer. All of these biomarkers will be used to help determine if you are eligible to join the trial. For more information about what a biomarker is, please visit What is a biomarker?

To be eligible for this trial, your cancer needs to be one of the following:

  1. MammaPrint High Risk score
  2. MammaPrint Low Risk score and ER negative
  3. MammaPrint Low Risk score and ER positive and Her2 positive

If your cancer does not match one of the groups listed or you have evidence of cancer in another part of your body, other than your lymph nodes, you will not be eligible to join the I-SPY 2 TRIAL. Please discuss other treatment options with your doctor.

Treatment Phase

If you are found to be eligible for the treatment phase of this study, you will be assigned to receive either standard chemotherapy or standard chemotherapy with an investigational drug before having surgery. Standard chemotherapy in this trial is Paclitaxel, with Trastuzumab if you are Her2 positive, followed by Anthracycline and Cyclophosphamide, also known as AC. For more information about having treatment before surgery, visit What is neoadjuvant therapy?

You will be given a treatment consent form by your study doctor or study coordinator that will give you information about the drugs you have been assigned to receive. If you decide to join the treatment phase of this trial, your tumor will be monitored by having multiple MRI scans throughout your treatment. You will also have additional blood draws and 1 additional core biopsy for research purposes. Below is a diagram of all of the study procedure you would have while you are in this trial.

I-SPY 2 TRIAL Study Procedures

I-SPY 2 TRIAL Study Procedure

Post-Surgery

After you have surgery, you and your doctors will determine what, if any, additional treatment would be in your best interest. You may be eligible for other clinical trials. To find out more information about other clinical trials for which you may be eligible, visit breastcancertrials.org.

I-SPY 2 Patient Study Schedule

I-SPY 2 Patient Schedule

Commonly Asked Questions about Participating in the I-SPY 2 TRIAL

If I join I-SPY 2, how long will I be in the study?
The screening phase of this study will last about 2 weeks. If you are found to be eligible and join the treatment phase of this study, it will last until you have surgery, about 6 months.

After your surgery, you and your doctors will choose what further treatment, if any, you will receive. A study coordinator will continue to monitor your health for 5 years by getting records from your regular visits with your doctors.

If I join I-SPY 2, how soon will I be able to start my treatment?
The screening phase of this study will last about 2 weeks. This time is used to find out what your tumor characteristics are and to assign you a study treatment. This time is also used for you and your doctor to do other standard tests and procedures needed before you start treatment. Deciding to join the screening phase of I-SPY 2 should not delay your treatment.

If I join I-SPY 2, how likely am I to receive an investigational drug?
Patients in I-SPY 2 will be assigned to standard chemotherapy or standard chemotherapy with an investigational drug. You will have an 80% chance of receiving investigational drug and a 20% chance of receiving just standard chemotherapy. A patient’s assigned treatment will depend on their tumor characteristics. The study will learn how effective the treatments are for the group of women who received them based on the information gathered from the multiple MRI scans and the amount of cancer that remains at the time of their surgery. Future patients entering the study have a higher chance of being assigned to the treatments that appear to be working for the group of women with similar tumor characteristics who have already received these treatments. This will hopefully allow us to provide better treatment for patients in this trial and for patients in the future. The investigational treatments may be better than, worse than, or no different than standard chemotherapy. The goal of the I-SPY 2 TRIAL is to find out which investigational treatment(s), if any, are better than standard chemotherapy.

How does the I-SPY 2 TRIAL assign which treatment I receive?
After you have completed the required tests and procedures during the screening phase and it is determined you are eligible for the treatment phase, a computer will randomize you to a treatment group, taking into account your tumor characteristics. By doing this, you have a higher chance of receiving treatment that targets your particular type of tumor. The tumor characteristics we will use are ER, PR, and Her2 status, along with MammaPrint risk score. Being randomized means that you will be put into a treatment group by chance.

Can I choose which treatment I want to receive?
No. A computer will randomize you into a treatment group. Once you are put into a treatment group, you must receive the treatment assigned to you in order to continue participating in the trial. We do not know yet which investigational drugs best treat which tumor types. The purpose of this trial is to learn this and make the drugs that are effective available to those who will benefit from them.

Can I switch investigational drugs during the treatment phase of I-SPY 2?
After you have been randomized to a treatment group, you will not be allowed to switch treatment groups as part of this study. If you or your doctor feel that is not in your best interest to continue in the treatment phase of this trial, you can stop participating in the trial at any time. Your participation in any clinical trial is voluntary.

Does my participation in I-SPY 2 affect other patients in I-SPY 2?
The I-SPY 2 TRIAL is designed to learn from every patient as they complete the treatment phase of the trial. How each patient responds to the treatment she was assigned, will impact future women who join the trial. A patient’s response to her treatment is determined by measuring the size of her tumor by MRI over the course of her treatment and by measuring the amount of tumor left at the time of her surgery.

You could have a positive response to a treatment, meaning your tumor gets smaller. You could have a negative response to a treatment, meaning your tumor does not get smaller or becomes larger. If you have a positive response to your treatment, future women that join this study with similar tumor characteristics to you will have a greater chance of being randomized to the same treatment group as you. On the other hand, if you have a negative response to a treatment, future women that join the study who have a similar tumor as yours will have a smaller chance of being randomized to the same treatment as you. This type of randomization is called adaptive randomization. This is how the study is able to learn from each patient while she is in the study. This will allow the study to test several investigational drugs in a short period of time and may help tailor breast cancer treatment for patients.

If I join I-SPY 2, how many MRI scans will I have, and will I know the results?
You will have 1 MRI scan as part of the screening phase, and another 3 as part of the treatment phase:

  1. First MRI scan: During the screening phase of this study, before you start treatment.
  2. Second MRI scan: At the end of your 3rd week of treatment.
  3. Third MRI scan: In between your 2 different types of treatment.
  4. Fourth MRI scan: Before you have surgery.

All MRI scan results will be available to you and your doctors. For more information about MRI scans, visit MRI scans.

If I join I-SPY 2, how many times will tissue be collected, and how will the tissue be collected?
You will have a total of 2 research core biopsies. Tissue will also be taken at the time of your surgery:

  1. First core biopsy: Done during the screening phase of this study, before you start treatment, to make sure you are eligible to join the treatment phase of this study.
  2. Second core biopsy: At the end of your 3rd week of treatment.
  3. Tissue sampled at surgery: At the time of your surgery.

For each study core biopsy, a needle about the size of pencil lead (diameter of 1.6 mm) will be inserted into your breast 4 times. A small amount of tissue will be removed each time. This procedure will be done with local anesthetic to minimize any discomfort and pain you may have from the biopsy.

A tissue sample will also be collected at the time of your surgery. This means that you may have your tissue collected for a total of 3 times if you participate in both the screening and treatment phases of this study.

If I join I-SPY 2, how many times will blood be collected for research purposes, and how will the blood be collected?
You will have blood collected for research 1 time during the screening phase, and 3 more times during the treatment phase of this study. This is in addition to the blood draws required as part of you standard treatment. To help reduce the number of times you will be pricked with a needle, the study will collect your blood at the time your catheter is placed for your study MRI scans or during a routine blood test.

This trial is called I-SPY 2. What was I-SPY 1 and what was learned from that trial?
The I-SPY 1 TRIAL started in 2003. The goal of I-SPY 1 was to see if we could predict how a woman would respond to standard chemotherapy by using multiple MRI scans and biomarkers. No investigational drugs were tested in I-SPY 1. The goal of I-SPY 2 is to take what was learned in I-SPY 1 and more quickly test which investigational drugs benefit patients and what tumor characteristics can be used to identify which future patients should receive those investigational drugs. The selection of biomarkers and MRI markers for I-SPY 2 is based, in part, on the results from I-SPY 1.

I-SPY 2 Study Procedures

What is a Magnetic Resonance Imaging (MRI) scan and why is it being used in I-SPY 2?

What is an MRI scan?
An MRI scan is a procedure that uses powerful magnet and radio waves linked to a computer to create clear and detailed cross-sectional images of the body. To visualize an MRI, think of your body as a loaf of bread with many slices. The MRI allows the doctor to see many different “slices” of a body part by taking pictures from outside the body. The “slices” can be displayed on a video monitor and saved on film for analysis.

For your breast MRI scan a contrast agent called gadolinium will be used to enhance the visibility of your cancer cells. The contrast agent is given through a small intravenous (IV) line placed in a vein in your arm.

What should I do before my MRI scan?
Before an MRI, eat normally and take your usual medications unless otherwise instructed. You will be given a hospital gown to wear or instructed to wear loose clothing without metal fasteners. Remove all accessories, such as jewelry and hair pins/clips. Also remove wigs, dentures, glasses, and hearing aids. Metal objects may interfere with the magnetic field during the exam, affecting the quality of the MRI images and the magnetic field may damage electronic items. To reduce your risk that these items may have, tell the technologist (the person performing the MRI) if you have:

  • any prosthetic joints
  • a pacemaker, defibrillator, or artificial heart valve
  • an implanted venous access device
  • an intrauterine device (IUD)
  • any metal plates, pins, screws, staples or bullets/shrapnel
  • tattoos or permanent make-up
  • a transdermal patch
  • anxiety in confined spaces (claustrophobia)

If you are pregnant or suspect you may be pregnant, tell the technologist.

What happens during my MRI scan?
A conventional MRI machine is a large cylindrical magnet with a central opening (similar to the shape of a donut). A sliding table rests in the middle opening. You will lie face down on the table and pillows or padding will be used to help keep you comfortable. The table will then move into the opening. The technologist will be in the next room and will see, hear, and speak to you at all times during the exam. During the exam you will need to remain very still. An MRI exam usually consists of several sequences, each lasting 2-15 minutes. Slight movement between sequences is allowed.

Time it takes for a Breast MRI scan: About 60 minutes (1 hour) in the scanner.

Noise during the MRI scan: You will hear loud tapping or thumping during the MRI exam. Earplugs or earphones may be provided to help block the noise. The technologist may talk to you during the scan.

Space during the MRI scan: The MRI opening is usually between 21-26 inches wide. The opening in the MRI scanner is 5-8 feet long. During the exam, you may feel “closed in” or claustrophobic. If this is a concern, speak to your doctor before your MRI. Your doctor may suggest medication so you can feel more comfortable during the MRI exam.

What happens after my MRI scan?
A radiologist, a doctor with specialized training in MRI and other imaging tests, will review and provide the results of all of your MRI scans done in this study. It will usually take a day or so for the report to be completed and sent to your doctors.

For further information, please visit The American College of Radiology Imaging Network.

If I join I-SPY 2, how many MRI scans will I have, and will I know the results?
You will have 1 MRI scan as part of the screening phase, and another 3 as part of the treatment phase:

  1. First MRI scan: During the screening phase of this study, before you start treatment.
  2. Second MRI scan: At the end of your 3rd week of treatment.
  3. Third MRI scan: In between your 2 different types of treatment.
  4. Fourth MRI scan: Before you have surgery.

All MRI scan results will be available to you and your doctors during your treatment.

Is it safe to have multiple MRI scans?
Doctors think that there are no additional side effects to having the multiple MRI scans as part of this trial. However, if you are concerned about the multiple of MRI scans used in this trial, you should talk to your doctor.

What is a biomarker and why is it being used in I-SPY 2?

What is a biomarker?
A biomarker is a characteristic of a cell that provides information about how the cell is behaving and can be measured in many ways. Biomarkers can be found in blood, body fluids, and tissue. Biomarkers can be present in normal and cancer cells. Biomarkers can be used to help diagnose a disease and monitor changes of the disease during treatment.

Biomarkers can be detected and measured by a variety of different methods. Some of these methods include testing done on tissue and blood samples. An example of a common biomarker used to determine if you are pregnant is HCG, Human Chorionic Gonadotropin. The presence or absence of this biomarker is tested using either a urine or blood sample. Other biomarkers can be tested with imaging techniques such as MRI, CT, and PET scans.

How and why are biomarkers being studied in I-SPY 2?
In I-SPY 2, standard and approved tests will be done on your tissue samples to find out if you are eligible to join the I-SPY 2 TRIAL. These include: Estrogen Receptor (ER) status, Progesterone Receptor (PR) status, Her2 receptor status, along with the TargetPrint Her2 and MammaPrint risk score. TargetPrint Her2 is another test of the Her2 receptor that looks at the amount of these genes in your tumor. MammaPrint is a test to find out if your cancer is at high risk for recurrence if you did not have any treatment, other than surgery, for your cancer. All of these biomarkers will be used to help determine if you are eligible to join the trial.

The MRI scans in this study will be used to help identify the response to chemotherapy by measuring the size of your tumor at different times during the course of your neoadjuvant treatment. How your tumor changes may be an important biomarker that could help decide if a future patient would benefit from therapy you received. For example, if the study finds that women who respond early to treatment will have a good chance of continuing to respond if they stay on that treatment, that biomarker could be used to help decide if future women should continue on that therapy or stop and possibly try a different therapy.

In I-SPY 2, research tests will also be done on your tissue and blood samples to find molecular biomarkers that may help identify your response to chemotherapy. The study hopes to use these molecular biomarkers to help identify which women in the future should receive certain therapies based on their specific molecular biomarkers. This will help to personalize treatment for breast cancer patients in the future.

If I join I-SPY 2, how many times will tissue be collected for research purposes, and how will the tissue be collected?
You will have a total of 2 research core biopsies. Tissue will also be taken at the time of your surgery:

  1. First core biopsy: Done during the screening phase of this study, before you start treatment, to make sure you are eligible to join the treatment phase of this study.
  2. Second core biopsy: At the end of your 3rd week of treatment.
  3. Tissue sampled at surgery: At the time of your surgery.

For each study core biopsy, a needle about the size of pencil lead (diameter of 1.6 mm) will be inserted into your breast 4 times. A small amount of tissue will be removed each time. This procedure will be done with local anesthetic to minimize any discomfort and pain you may have from the biopsy.

A tissue sample will also be collected at the time of your surgery. This means that you may have your tissue collected for a total of 3 times if you participate in both the screening and treatment phases of this study.

If I join I-SPY 2, how many times will blood be collected for research purposes, and how will the blood be collected?
You will have blood collected for research 1 time during the screening phase, and 3 more times during the treatment phase of this study. This is in addition to the blood draws required as part of your standard treatment. To help reduce the number of times you will be pricked with a needle, the study will collect your blood at the time your catheter is placed for your study MRI scans or during a routine blood test.

What will my tissue and blood samples be used for in this study?
A portion of the tissue collected during the screening phase will be used to run the MammaPrint risk score and TargetPrint Her2 test. A number of other research tests will also be done on your tissue and blood samples collected as part this study. These tests will help the researchers learn more about your cancer including molecular (cell) changes that occur in your tumor as a result of your treatment. The goal of these other research tests is to identify a biomarker(s) that can be used to predict a woman’s response to a specific therapy.

Will I be told the results of the research tests done from my tissue and blood samples?
After your initial diagnostic core biopsy and at the completion of your surgery, your doctors will receive a report that has information about the standard biomarkers: Estrogen Receptor (ER), Progesterone Receptor (PR), and Her2 receptor. Your MammaPrint risk score and TargetPrint result will also be shared with you and your doctors as part of the screening phase of I-SPY 2. These biomarkers will be used to decide what treatment you will be assigned.

Information about other research tests done on your tissue and blood samples will not be provided to you and will not affect the care that you receive. The study does not know what the results of the research tests mean to you and this is why they are being studied. The study will learn what the results of these research tests mean and how this information could be useful for future cancer patients.

What is neoadjuvant treatment and why it is being used in I-SPY 2?

Why will I receive treatment before surgery in I-SPY 2?
Although surgery has traditionally been done before starting chemotherapy, chemotherapy is now more often being given before surgery, called neoadjuvant chemotherapy. Research has shown that there is no overall survival difference if you receive chemotherapy before or after your surgery.

Furthermore, there are several advantages to the neoadjuvant approach as a choice for therapy.

  1. For women with large tumors, neoadjuvant therapy may shrink the tumor enough to allow you to have more surgical choices.
  2. Learning whether or not your tumor has responded to chemotherapy can help you and your doctors determine if you need any more treatment after surgery.
  3. In a research setting, neoadjuvant therapy allows researchers to learn the potential value of the investigational drugs being tested by being able to monitor how your tumor responds to treatment.

Why will I receive 2 different chemotherapy treatments if I join I-SPY 2?
It is standard of care for women with locally advanced breast cancer to receive these 2 types of chemotherapy treatments as shown in the diagram above. The I-SPY 2 TRIAL is testing if adding an investigational drug to the first type of chemotherapy will help in treating certain types of breast cancer.

How does the I-SPY 2 TRIAL assign which treatment I receive?
After you have completed the required tests and procedures to find out if you are eligible for the treatment phase of this study, a computer will randomize you to a treatment group, taking into account your tumor characteristics. By doing this, you have a higher chance of receiving a treatment that targets your particular type of tumor. The tumor characteristics we will use are ER, PR, and Her2 status, along with MammaPrint risk score. Being randomized means that you will be put into a treatment group by chance.

After I complete my neoadjuvant treatment, what options are available to me for additional treatment?
If you have been treated with an investigational drug in this study, it may or may not limit you from getting other standard treatments used to treat breast cancer. Talk to your study doctors to find out more about how this could affect you. After you have surgery, you and your doctors will determine what, if any, additional treatment would be in your best interest. You may be eligible for other clinical trials. To find out more information about other clinical trials that you may be eligible for visit breastcancertrials.org

What are investigational drugs and why are they being used in I-SPY 2?

What should I know about investigational drugs used in I-SPY 2?
An investigational drug is a new drug that has not been approved by the Food and Drug Administration (FDA). The investigational drugs in this trial have been previously tested in people. By taking an investigational drug along with standard chemotherapy, there may be additional side effects than if you just took the standard chemotherapy. If you have been randomized to receive an investigational drug, you will receive a consent form that informs you of the investigational drug and all of the known side effects for that drug. Everyone taking part in this study will be watched carefully for any side effects. You should talk to your study doctor about any side effects you experience while taking part in this study.

If I join I-SPY 2, how likely am I to receive an investigational drug?
Patients will be assigned to standard chemotherapy or standard chemotherapy with an investigational drug. You will have an 80% chance of receiving an investigational drug and a 20% chance of receiving just standard chemotherapy. A patient’s assigned treatment will depend on their tumor characteristics. The study will learn how effective the treatments are for the group of women who received them based on the information gathered from the multiple MRI scans and the amount of cancer that remains at the time of their surgery. Future patients entering the study have a higher chance of being assigned to the treatments that appear to be working for the group of women with similar tumor characteristics who have already received these treatments. This will hopefully allow us to provide better treatment for patients in this trial and for patients in the future. The investigational treatments may be better than, worse than, or no different than standard chemotherapy. The goal of the I-SPY 2 TRIAL is to find out which investigational treatment(s), if any, are better than standard chemotherapy.

If I do receive an investigational drug(s), what will it be and what are the potential short and long term side effects?
If you have been assigned to receive an investigational drug, a study doctor will tell you what the drug is and discuss in detail the treatment and all of the known side effects of that treatment in the consent form. This information will also be available in the consent form. It is not known if the investigational drugs are better than or worse than standard chemotherapy; this is why they are being studied.

Can I switch investigational drugs during the treatment phase of I-SPY 2?
After you have been randomized to a treatment group, you will not be allowed to switch treatment groups as part of this study. If you or your doctor feel that it is not in your best interest to continue in the treatment phase of this trial, you can stop participating in the trial at any time. Your participation in any clinical trial is voluntary.

Investigational drugs may enter and leave the I-SPY 2 TRIAL. What does that mean to me?
The I-SPY 2 TRIAL is designed to test multiple investigational drugs over the course of the trial to learn which drugs may or may not benefit future patients. Once the study has gathered enough information about a particular investigational drug, it will leave the trial and another new investigational drug will enter the trial. This means that if you received an investigational drug it may leave the trial before the trial is completed.

There are 3 reasons why investigational drugs may leave the I-SPY 2 TRIAL:

  1. An investigational drug can leave the trial because it has been shown to be beneficial in patients in the I-SPY 2 TRIAL and will likely be successful in a specific larger trial.
  2. An investigational drug can leave the trial because it has not been shown to be significantly more beneficial to patients in the I-SPY 2 TRIAL. This includes if the investigational drug is worse than just standard chemotherapy. While a few individual patients may have a good response to a drug, the drug will leave because there does not appear to be a benefit for the majority of the patients in this study.
  3. An investigational drug may be removed from the trial if patients have serious side effects to the drug.

Will I know if an investigational drug I am getting has left the I-SPY 2 TRIAL, and what do I do once it leaves?
The study team will tell you if the investigational drug you are assigned to is leaving the trial and the reason why.

If the investigational drug is removed from the study while you are still receiving the investigational drug, you have 2 choices:

  1. Continue taking the investigational drug and continue the treatment phase of the trial. This option will not be available to you if the drug was removed because it was found to have serious side effects in other patients.
  2. Stop taking the investigational drug and continue the treatment phase of the trial with just standard chemotherapy.

If the investigational drug is removed from the study because of severe side effects while you are still receiving the investigational drug, you will stop receiving the investigational drug immediately. You can choose to continue in the study and receive standard chemotherapy or stop participating in the study.

If you are still receiving neoadjuvant treatment as part of the study but you are no longer being treated with the investigational drug, you will also be told that the drug has left the trial and the reason why.

If you have any questions, contact your study doctors to discuss your treatment options. At any time, you have the choice to stop participating in this trial. You should talk to your study doctor before stopping treatment as part of this trial.