NSABP FB-11

A Phase II Randomized Study Evaluating the Biological and Clinical Effects of the Combination of Palbociclib with Letrozole as Neoadjuvant Therapy in Post-Menopausal Women with Estrogen-Receptor Positive Primary Breast Cancer

Patient Informed Consent Form

for use by

Independent Investigators

Consent Version Date: April 21, 2015

Instructions to Local Institutional Review Boards Regarding
Local IRB Review of Multicenter Clinical Trials
The NSABP Department of Site and Study Management (DSSM), provides the following instructions regarding the IRB approval process of this multicenter clinical trial.
Local IRBs and the investigator are permitted to make changes to the consent forms; however, the editorial changes must not alter the overall content or the intent of the information in the sample consent form. Note: The investigator must forward the local consent form to DSSM for approval before submitting to the IRB. Should an investigator or local IRB delete or make a substantive modification of the information contained in the risks or alternative treatments sections of the consent form, this must be justified in writing by the investigator or the IRB and then approved by the IRB. The IRB is responsible for reflecting in the IRB minutes the justification for, and approval of, such deletions or modifications. The investigator is responsible for forwarding copies of substantive IRB-approved changes with their justifications to the DSSMimmediately. It is the responsibility of the principal investigator and the IRB to determine what constitutes a substantive change. Any conflict between the two groups concerning this decision would be resolved by DSSM staff.
Upon receipt of these documents,DSSM staff will review and approve the changes and their justifications with input (as needed) from government agencies.

ConfidentialNSABP FB-11

NSABP FB-11

Version Date: 04/21/15

IRB Approved: 00/00/00

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NSABP SAMPLE CONSENT

Consent Form

for

A Phase II Randomized Study Evaluating the Biological and Clinical Effects of the Combination of Palbociclib with Letrozole as Neoadjuvant Therapy in Post-Menopausal Women with Estrogen-Receptor Positive Primary Breast Cancer

NSABP FB-11 is a clinical trial, which is a type of research study. You are being asked to take part in this study because you have early invasive, estrogen receptor positive (ER-positive), HER2-negative breast cancer, you are post-menopausal, and you have not had treatment or surgery to remove the tumor.

This research study is only for women with estrogen receptor-positive, HER2-negative breast cancer. Neoadjuvant therapies are therapies given before surgery. Estrogen is a female hormone produced by the body. Estrogen receptor-positive (ER-positive) breast cancer cells have a significant number of special proteins inside called hormone receptors. Estrogen attaches to hormone receptors and causes breast cancer cells to grow. HER2-negative breast cancer means that the tumor does not have too many copies of the HER2 gene or too much HER2 protein. Knowing these characteristics about your breast cancer will help doctors plan the treatment that will be best for you.

Your study doctor will explain the research study to you. Research studies include only people who choose to take part. Please take your time to make your decision about taking part. You may discuss your decision with your friends and family. You can also discuss it with your health care team. If you have any questions, you can ask your study doctor for more explanation.

Who is conducting the study?

The NSABP Foundation, Inc. (NSABP) Department of Site and Study Management (DSSM) is conducting this clinical trial in the United States (US) and Canada. The Royal Marsden NHS Foundation Trustand the Institute of Cancer Research (ICR) areconducting this study in the United Kingdom (UK).

(NSABP DSSM institutions must supply appropriate information regarding who is conducting the trial locally.)

Why is this study being done?

FB-11 will look at effects the combination of palbociclib and letrozole may have on
ER-positive/HER2-negative breast cancer tumors that have not yet been treated. Letrozole is a type of endocrine therapy called an aromatase inhibitor (AI) and is standard treatment for
post-menopausal women with ER-positive/HER2-negativebreast cancer. Palbociclib is a targeted therapy for ER-positive/HER2-negative breast cancer. A targeted therapy stops cancer cells from growing by targeting and blocking the proteins that help cancer cells to grow. Palbociclib is approved by the U.S. Food and Drug Administration (FDA) for use in combination with letrozole to treat advanced and metastatic breast cancer.

NSABP FB-11

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Palbociclib is considered investigational in this study because it is not approved by the FDA for use in early breast cancer.

This study is being done for the following reasons:

  • The purposeof the study is to compare the effects of 14 weeks of letrozole with or without palbociclib on the protein markers associated with ER-positive/HER2-negative breast cancer.
  • The second purpose of the study is to compare how breast cancer responds to letrozole and palbociclib following 14 weeks of study therapy.
  • Testing your blood and tumor samples is an important part of the study in order to look at the changes on the proteins associated with breast cancer. The study includes special research tests using samples from your blood and breast tumor.

The following collection and submission of breast tumor samples are study requirements:

biopsies performed at three time points to obtain fresh breast tumor samples: before you begin study treatment, once during treatment (Week 2), and after you complete study treatment (around Week 14)

tumor removed during your breast surgery. Breast tissue removed at the time of your surgery will be examined in the hospital's standard manner. If any tumor a centimeter in size (about one half of an inch) or larger is found during surgery, a small sample of this tumor will be sent to NSABP.

The following collection and submission of blood samples are study requirements:

before you begin study treatment,

once during treatment (Week 2), and

after you complete study treatment (around Week 14).

These required research samples will be explained to you in more detail later in this consent form.

How many people will take part in the study?

Approximately 306 women in the US, Canada, and the United Kingdom will take part in this study.

What will happen if I take part in this research study?

Before you begin the study:

You will need to have the following tests and exams to find out if you can be in the study. These tests and exams are part of regular cancer care and may be done even if you do not join the study. If you have had some of them recently, they may not need to be repeated. This will be up to your study doctor.

  • Medical history
  • Physical examination
  • Blood tests:

to check your blood counts

to check how well your kidneys and liver are working

to measure the electrolytes (salts and other substances normally found in your blood), proteins, and blood glucose (sugar)

  • Electrocardiogram (EKG) to check your heart
  • Mammary (Breast) Ultrasound to measure your breast tumor
  • Blood test (to verify you are post-menopausal, if necessary)

If the tests and exams show that you can be in the study and if you choose to take part, you will also have research blood samples collectedas described later in this consent form. The blood samples are not for regular cancer care and are required to be a part of this study.

A biopsy of your breast tumor will also be performed at this time. The tumor biopsy is not for regular cancer care and is required to be a part of this study.

You will begin your study therapy about a week after your biopsy.

You will be "randomized" to one of four study arms described in the following sections. Randomization means that you are put into a study arm by chance. A computer program will place you in one of the study arms. Neither you nor your study doctor can choose the study arm. Patients participating in this study will be randomized in a 3:2:2:2 sequence. This means that for every 3women who receive standard therapy, (letrozole [Arm A]),2 women will be randomized to receive letrozole in addition to the investigational therapy, palbociclib, in each of the three different treatment schedules as described below as Arm B, Arm C, and Arm D.

In other words, about 102women will be randomized to Arm A and approximately 68 women will be randomized to each of the other treatment arms (Arms B, C, and D).

You will receive your study therapy according to a schedule described in the next sections.

A summary of the study therapy is outlined below.

Study Therapy
Arm A / Arm B / Arm C / Arm D
Letrozole(only)
1 tablet daily
For
14 weeks / Letrozole 1 tablet daily for 2 weeks / Palbociclib 1 capsule daily for 2 weeks / Letrozole 1 tablet daily
And
palbociclib
1 capsule
(daily for 3 weeks followed
by1week off schedule)
For
14 weeks
Followed by
Letrozole 1 tablet daily
And
palbociclib
1 capsule
(daily for 3 weeks
followed by1 week off schedule)
For 12 weeks
Surgery
Post-surgical treatment as prescribed by your doctor (not study therapy)

Your study team will monitor how you are feeling while you are taking study therapy (letrozole/palbociclib). The study therapy dose of letrozole is 2.5mg (1 tablet) daily. The study therapy dose of palbociclib is 125mg (1 capsule) daily. The palbociclib dose may be adjusted if you experience certain side effects which are described later in the consent form.

Study Therapy Arm A:

(Letrozole x 14 weeks)

You will take 1 letrozole tablet daily for 14 weeks.

Keep track of the letrozole tables that you take. This can be done by writing each dose in a diary or on a calendar or other type of record.

Study Therapy Arm B:

(Letrozole x 2 weeks followed by letrozole/palbociclib x 12 weeks)

For the first two weeks of the study:

  • You will take 1 letrozole tablet daily.

For the next two weeks:

  • You will continue to take 1 letrozole tablet daily (no off days) and start taking 1 palbociclibcapsule daily for 1 week (7 days) with 1 week (7 days) off. This will complete Cycle 1 (28 days).

Following Cycle 1:

You will continue to take1 letrozole tablet daily (no days off) and 1 palbociclib capsule daily for

3 weeks (21 days) on and 1 week (7 days) off for an additional 10 weeks.

Study Therapy Arm C:

(Palbociclib x 2 weeks followed by letrozole/palbociclib x 12 weeks)

For the first two weeks of the study:

  • You will take 1 palbociclib capsule daily (14 days total).

Following the two weeks of palbociclib therapy:

  • You will take 1 letrozole tablet daily (no off days) and continue to take palbociclib (1 capsule daily) for 1 additional week (7 days), then 1 week (7 days) off. This will complete Cycle 1 (28 days).

Following Cycle 1:

You will continue to take 1 letrozole tablet daily(no days off) and 1 palbociclib capsule daily for
3 weeks (21 days) on and 1 week (7 days) off for an additional 10 weeks.

Study Therapy Arm D:

(Letrozole and palbociclib x 14 weeks)

You will take 1 letrozole tablet daily (no off days). You will also take 1 palbociclib capsule daily for 3 weeks (21 days) with 1 week (7 days) off for 14 weeks.

Instructions for taking palbociclib for patients on Study Arms B, C, or D:

  • Take the palbociclib capsules with foodand a full glass of waterat the same time each day (preferably in the morning before noon).
  • Swallow palbociclib capsules whole;do not chew them. Do not take any capsules that are cracked or broken. Capsules that are cracked or broken should be returned to your Study Team to be replaced.
  • Never share your study medication with any one.
  • Keep track of the palbociclib capsules and letrozole tablets that you take. This can be done by writing each dose in a diary or on a calendar or other type of record. You will also be required to bring back the bottles of palbociclib (empty or containing any remaining capsules to be counted).
  • If you have forgotten your dose and remember more than 12 hours later, do not take your dose that day but continue the following day. You should notify your study doctor whenever this occurs.
  • If you vomit, you should not take another dose that day and you should let your doctor know.

There are other medications, fruits (for example, grapefruit and products containing grapefruit juice), and other substances, such as St. John's Wort, that you must avoid while you are taking palbociclib. Some medications can decrease or increase the effects of palbociclib. It is important that you tell your doctor and study team about all the medications, vitamins and herbal supplements you are taking before you begin study therapy and throughout your participation in the study.

Your study doctor or nurse will talk with you more about this and will review with you all medications you are taking before you join the study.

Tests and exams during the study:

You will need to have the following tests and exams at various times during the study. Your study team will review this with you. They are part of regular cancer care.

  • Physical examinationson a regular schedule during study therapy
  • Blood tests on a regular schedule during study therapy to check for treatment side effects
  • A breast ultrasoundto measure whether your breast cancer responded to the study therapy.
  • Electrocardiogram (EKG) at 6 weeks and at the end of study therapy (Week 14).

You will also need the following tests that are not part of regular cancer care and are being done for the purpose of this study:

  • Required research blood sample prior to beginning study therapy, at Week 2 and Week 14.
  • Required tumor biopsies will be performed prior to beginning study therapy, at Week 2 and Week 14. If any tumor a centimeter (about one-half inch) or larger is found during surgery, a small sample of this tumor will be sent to NSABP.
  • If you decide to stop study therapy, you will be asked to have an optionaltumor biopsy performed and a blood sample collected for research at that time. A separate consent form will be provided to you. The decision regarding further treatment, including surgery will be up to you and your doctor.

About 2 to 3 weeks after you complete study therapy, you will have surgery for your breast cancer. You will have either a lumpectomy or mastectomy to remove any remaining tumor. Nearby lymph nodes may also be removed. The decision about what type of surgery you will have is up to you and your doctor.

After surgery: Your doctor may discuss any additional therapy after your surgery. This is not part of study therapy.

About 30 days after your last dose of study therapy, you will need to have a physical examination, blood tests, and talk about any side effects.

About 1 year after joining the study, your study doctor or member of the study team will check to see how you are doing. You will also have a blood test to check your blood counts which is part of regular cancer care.

How long will I be in the study?

You will be in the study for about 2 years. During that time you will receive study therapy for
14 weeks before you have surgery. You will have follow-up tests and exams as described earlier in this consent form, at approximately 30 days after you complete study therapy and 1 year after joining the study.

If you stop study therapy, NSABP would still like to know how you are doing. You will continue to have follow-up tests and exams as described earlier in this consent form at approximately 30 days after your last dose of study therapy, and 1 year after joining the study.

Can I stop being in the study?

Yes. You can decide to stop at any time. Tell your study doctor if you are thinking about stopping or decide to stop. He or she will tell you how to stop safely. It is important to tell your study doctor if you are thinking about stopping so any risks from the therapy can be evaluated by your study doctor. Another reason to tell your study doctor that you are thinking about stopping is to discuss what follow-up care and testing could be most helpful for you.

You can choose to withdraw from the study in one of two ways:

  • You can stop your study treatment, but still allow your study doctor to report about your health to NSABP; or
  • You can stop your study treatment and request that no new information be reported to NSABP. Any information collected for this study up to the time you withdraw from the study will continue to be used.

Can anyone else stop me from being in the study?

Your study doctor may stop you from taking part in this study at any time if he or she believes it is in the best interest of your health, if you do not follow the study rules, or if the study is stopped by NSABP.