The FB-11 study is a Phase II, randomized, open label, four arm study to examine the
biological and clinical effect of neoadjuvant letrozole with or without palbociclib in the
first-line treatment of estrogen-receptor (ER) positive, HER2-negative early invasive breast
cancer. The co-primary aims of this study are to to compare the changes in the
proliferation marker Ki67, and to compare clinical response after 14 weeks of therapy with
letrozole with or without palbociclib.
The FB-11 study initiative is a joint partnership between the NSABP Foundation, Inc. (NSABP)
Department of Site and Study Management (DSSM) and United Kingdom (UK) co-investigators at
the Royal Marsden NHS Foundation Trust and the Institute of Cancer Research (ICR). Parallel
protocols will be conducted in the US and Canada (FB-11), and the UK (PALLET) with joint
analysis of interim and final data.
Postmenopausal women, newly diagnosed with ER-positive/HER2-negative early breast cancer,
who are suitable candidates for neoadjuvant endocrine therapy will be invited to join the
FB-11/PALLET trial. Approximately 306 patients will be accrued to this study. Each
collaborative group will recruit at least 1/3 and no more than 2/3 of the target accrual.
Patients will be randomized to one of four treatment arms (3:2:2:2 ratio). Treatment in the
first 14 weeks of neoadjuvant therapy will be:Arm A Letrozole alone; Arm B Letrozole for 2
weeks followed by letrozole + palbociclib to week 14; Arm C Palbociclib for 2 weeks followed
by letrozole + palbociclib to week 14; Arm D Letrozole + palbociclib to week 14.
Letrozole will be administered orally as a 2.5mg daily tablet. Palbociclib will be
administered orally as 125mg capsules, daily on a schedule of 3 weeks (21 days) on, 1 week
(7 days) off of a 4 week [28 day] cycle.
The end of study therapy for patients in Arm A will be completion of week 14. Patients in
Arms B, C, and D will complete study therapy following 14 days of palbociclib in the final
treatment cycle past 14 weeks if treatment delays have occurred.
Note: After week 14 (end of study therapy) all patients should continue letrozole until
surgery. Letrozole is not considered study therapy beyond completion of week 14 for Arm A
or after 14 days of palbociclib in the final treatment cycle for patients in Arms B, C, and
Following completion of study therapy, surgery will be scheduled for 15-18 weeks
post-randomization. Post-surgical treatment will be at discretion of treating clinician,
following local protocols, and not influenced by allocation of treatment within the
Toxicity will be graded according to the National Cancer Institute (NCI) Common Terminology
Criteria for Adverse Events version 4.0 (CTCAE v4.0).
- Patients must be postmenopausal women defined as: Age 56 or older with no
spontaneous menses for at least 12 months prior to study entry; or Age 55 or younger
with no menses for at least 12 months prior to study entry (e.g., spontaneous or
secondary to hysterectomy) and with a documented estradiol level in the
postmenopausal range according to local institutional/laboratory standard; or Age
greater than or equal to 18 with documented bilateral oophorectomy.
- Operable ER-positive/HER2- negative, invasive early breast cancer, suitable for
neoadjuvant AI treatment. HER2-negative as determined by American Society of
Clinical Oncology - College of American Pathologists (ASCO-CAP) guidelines.
- No known severe hypersensitivity reactions to compounds similar to palbociclib or
palbociclib excipients or to endocrine treatments.
- A breast tumor with an ultrasound size of at least 2.0 cm.
- Patients must have the ability to swallow oral medication.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- At the time of randomization, blood counts performed within 4 weeks prior to
randomization must meet the following criteria: absolute neutrophil count (ANC) must
be greater than or equal to 1500/mm3; Platelet count must be greater than or equal to
100,000/mm3; Hemoglobin must be greater than or equal to 10 g/dL.
- international normalized ratio (INR) must be within normal limits of the local
- The following criteria for evidence of adequate hepatic function performed within 4
weeks prior to study entry must be met: total bilirubin must be less than or equal to
upper limit of normal (ULN) for the lab unless the patient has a bilirubin elevation
greater than ULN to 1.5 x ULN due to Gilbert's disease or similar syndrome involving
slow conjugation of bilirubin; and alkaline phosphatase must be must be less than or
equal to 1.5 x ULN for the lab; and aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) must be less than or equal to 1.5 x ULN for the lab.
- Serum creatinine performed within 4 weeks prior to study entry must be less than or
equal to 1.25 x ULN or estimated creatinine clearance less than 60 mL/min (as
calculated using the method standard for the institutions).
- Active hepatitis B or hepatitis C with abnormal liver function tests.
- HIV positive patients receiving antivirals.
- Premenopausal or peri-menopausal women.
- Inflammatory/inoperable breast cancer.
- HER2-positive as determined using ASCO-CAP Guidelines.
- Concurrent use (defined as use within 4 weeks prior to baseline tissue sample being
taken) of hormone replacement therapy (HRT) or any other estrogen-containing
medication (including vaginal estrogens)
- Prior endocrine therapy for breast cancer.
- Any invasive malignancy within previous 5 years (other than basal cell carcinoma or
cervical carcinoma in situ).
- Other nonmalignant systemic disease that would preclude the patient from receiving
study treatment or would prevent required follow up such as: Active infection or
chronic infection requiring chronic suppressive antibiotics; Malabsorption syndrome,
ulcerative colitis, inflammatory bowel disease, resection of the stomach or small
bowel, or other disease or condition significantly affecting gastrointestinal
function; Chronic daily treatment with corticosteroids with a dose of greater than or
equal to 10 mg/day methylprednisolone equivalent (excluding inhaled steroids);
Seizure disorders requiring medication.
- Diagnosis by fine needle aspiration (FNA) alone or excisional biopsy or lumpectomy
performed prior to study entry.
- Surgical axillary staging procedure prior to study procedure (with exception of FNA
or core biopsy).
- Definitive clinical or radiologic evidence of metastatic disease.
- History of ipsilateral invasive breast cancer regardless of treatment or ipsilateral
ductal carcinoma in situ (DCIS) treated with radiotherapy or contralateral invasive
breast cancer at any time.
- Any treatment, including radiotherapy, chemotherapy, and/or targeted therapy,
administered for the currently diagnosed breast cancer prior to study entry.
- Use of any medication or substances that are strong inhibitors or inducers of CYP3A
- Class III or Class IV myocardial disease as described by the New York Heart
Association; a recent history (within 6 months) of myocardial infarction, or
symptomatic arrhythmia at the time of randomization. Class III: Patients with
cardiac disease resulting in marked limitation of physical activity. Such patients
are comfortable at rest. Less than ordinary physical activity that causes fatigue,
palpitation, dyspnea, or anginal pain. Class IV: Patients with cardiac disease
resulting in inability to perform any physical activity without discomfort. Symptoms
of cardiac insufficiency or anginal syndrome may be present even at rest.
- QTc greater than 480 msec or a family or personal history of long or short QT
syndrome, Brugada syndrome or know history of QTc prolongation, or Torsade de Pointes
- The investigator should assess the patient to determine if she has any psychiatric or
addictive disorder or other condition that, in the opinion of the investigator, would
preclude her from meeting the study requirements.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Female