Breast Cancer Clinical Trial

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

Summary

This study will look at effects the combination of palbociclib and letrozole may have on estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer tumors which 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-negative breast cancer.

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Full Description

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 D.

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 FB-11/PALLET study.

Toxicity will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0).

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

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 laboratory ranges.
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).

Exclusion Criteria:

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 isoenzymes.
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 (TdP).
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.

Study is for people with:

Breast Cancer

Phase:

Phase 2

Estimated Enrollment:

307

Study ID:

NCT02296801

Recruitment Status:

Completed

Sponsor:

NSABP Foundation Inc

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There are 52 Locations for this study

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Long Beach Memorial Medical Center-Todd Cancer Institute
Long Beach California, 90806, United States
University of Miami Hospital and Clinics - Sylvester Comprehensive Cancer Center
Miami Florida, 33136, United States
Cancer Care Specialists of Central Illinois
Decatur Illinois, 62526, United States
Norton Healthcare Pavillion
Louisville Kentucky, 40202, United States
Norton Cancer Institute - Suburban, Norton Medical Plaza II
Louisville Kentucky, 40207, United States
Norton Cancer Institute - Brownsboro Medical Plaza I
Louisville Kentucky, 40241, United States
Metro-Minnesota CCOP
Saint Louis Park Minnesota, 55416, United States
Hope Women's Cancer Centers
Asheville North Carolina, 28806, United States
Providence Oncology and Hematology Clinic
Portland Oregon, 97213, United States
Pinnacle Health Ortenzio Cancer Center
Mechanicsburg Pennsylvania, 17050, United States
Allegheny General Hospital
Pittsburgh Pennsylvania, 15215, United States
University of Pittsburgh
Pittsburgh Pennsylvania, 15232, United States
Women and Infants Hospital of Rhode Island
Providence Rhode Island, 02905, United States
Baylor College of Medicine
Houston Texas, 77030, United States
Joe Arrington Cancer Research and Treatment Center
Lubbock Texas, 79410, United States
Sentara Martha Jefferson Hospital-Phillips Family Cancer Center
Charlottesville Virginia, 22911, United States
Virginia Commonwealth University
Richmond Virginia, 23298, United States
Swedish Cancer Institute
Seattle Washington, 98104, United States
West Virginia University
Morgantown West Virginia, 26506, United States
Centre Hospitalier de l'Universite de Montreal
Montreal Quebec, H2W-1, Canada
Jewish General Hospital
Montreal Quebec, H3T 1, Canada
McGill University Health Center
Montreal Quebec, H4A 3, Canada
CHU de Quebec - Universite Laval
Quebec City Quebec, G1S 4, Canada
Milton Keynes Hospital
Milton Keynes Buckinghamshire, MK6 5, United Kingdom
Hinchingbrooke Hospital
Huntingdon Cambridgeshire, PE29 , United Kingdom
Royal Cornwall Hospital, Treliske
Truro Cornwall, TR1 3, United Kingdom
Royal Devon and Exeter Hospital
Exeter Devon, EX2 5, United Kingdom
Royal Sussex County Hospital
Brighton East Sussex, BN2 5, United Kingdom
Southend Hospital
Westcliff-on-Sea Essex, SS0 0, United Kingdom
Darent Valley Hospital
Dartford Kent, DA2 8, United Kingdom
Maidstone Hospital
Maidstone Kent, ME16 , United Kingdom
Royal Liverpool University Hospital
Liverpool Merseyside, L7 8X, United Kingdom
James Paget University Hospital
Great Yarmouth Norfolk, NR31 , United Kingdom
Musgrove Park Hospital
Taunton Somerset, TA1 5, United Kingdom
Weston General Hospital
Weston-Super-Mare Somerset, BS23 , United Kingdom
The Royal Marsden Hospital
Sutton Surrey, SM2 5, United Kingdom
Salisbury Hospital
Salisbury Wiltshire, SP2 8, United Kingdom
Kidderminster Hospital
Kidderminster Worcestershire, DY11 , United Kingdom
Alexandra Hospital
Redditch Worcestershire, B98 7, United Kingdom
Worcestershire Royal Hospital
Worcester Worcestershire, WR5 1, United Kingdom
Belfast City Hospital
Belfast , BT9 7, United Kingdom
Royal Bournemouth Hospital
Bournemouth , BH7 7, United Kingdom
Western General Hospital (Edinburgh Cancer Centre)
Edinburgh , EH4 2, United Kingdom
St James' University Hospital
Leeds , LS9 7, United Kingdom
Barnet Hospital
London , EN5 3, United Kingdom
Whittington Hospital
London , N19 5, United Kingdom
University College London Hospitals
London , NW1 2, United Kingdom
The Royal Marsden Hospital
London , SW3 6, United Kingdom
Charing Cross Hospital
London , W8 6R, United Kingdom
Nottingham University Hospitals NHS Trust, City Campus
Nottingham , NG5 1, United Kingdom
Derriford Hospital
Plymouth , PL6 8, United Kingdom
Singleton Hospital
Swansea , SA2 8, United Kingdom

How clear is this clinincal trial information?

Study is for people with:

Breast Cancer

Phase:

Phase 2

Estimated Enrollment:

307

Study ID:

NCT02296801

Recruitment Status:

Completed

Sponsor:


NSABP Foundation Inc

How clear is this clinincal trial information?

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