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

NCT02296801

Last updated date
Study Location
Long Beach Memorial Medical Center-Todd Cancer Institute
Long Beach, California, 90806, United States
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Breast Cancer, Breast Carcinoma, Breast Tumors
Sex
Female
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- 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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- 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.

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Breast Cancer, Breast Carcinoma, Breast TumorsA 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
NCT02296801
  1. Long Beach, California
  2. Miami, Florida
  3. Decatur, Illinois
  4. Louisville, Kentucky
  5. Louisville, Kentucky
  6. Louisville, Kentucky
  7. Saint Louis Park, Minnesota
  8. Asheville, North Carolina
  9. Portland, Oregon
  10. Mechanicsburg, Pennsylvania
  11. Pittsburgh, Pennsylvania
  12. Pittsburgh, Pennsylvania
  13. Providence, Rhode Island
  14. Houston, Texas
  15. Lubbock, Texas
  16. Charlottesville, Virginia
  17. Richmond, Virginia
  18. Seattle, Washington
  19. Morgantown, West Virginia
  20. Montreal, Quebec
  21. Montreal, Quebec
  22. Montreal, Quebec
  23. Quebec City, Quebec
  24. Milton Keynes, Buckinghamshire
  25. Huntingdon, Cambridgeshire
  26. Truro, Cornwall
  27. Exeter, Devon
  28. Brighton, East Sussex
  29. Westcliffe-on-sea, Essex
  30. Dartford, Kent
  31. Maidstone, Kent
  32. Liverpool, Merseyside
  33. Great Yarmouth, Norfolk
  34. Taunton, Somerset
  35. Weston-Super-Mare, Somerset
  36. Sutton, Surrey
  37. Salisbury, Wiltshire
  38. Kidderminster, Worcestershire
  39. Redditch, Worcestershire
  40. Worcester, Worcestershire
  41. Belfast,
  42. Bournemouth,
  43. Edinburgh,
  44. Leeds,
  45. London,
  46. London,
  47. London,
  48. London,
  49. London,
  50. Nottingham,
  51. Plymouth,
  52. Swansea,
Female
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
Brief 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.
Detailed 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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Breast Cancer
  • Breast Carcinoma
  • Breast Tumors
Intervention  ICMJE
  • Drug: Letrozole
  • Drug: palbociclib
Study Arms  ICMJE
  • Active Comparator: A: letrozole
    letrozole 2.5 mg tablet orally daily for 14 weeks
    Intervention: Drug: Letrozole
  • Experimental: B: letrozole then letrozole + palbociclib
    letrozole 2.5 mg orally daily plus beginning 2 weeks after starting letrozole, palbociclib 125 mg capsule orally daily for 1 week then 1 week off, then a 3 weeks on and 1 week off cycle for a total of 14 weeks from start of letrozole therapy
    Interventions:
    • Drug: Letrozole
    • Drug: palbociclib
  • Experimental: C: palbociclib then letrozole + palbociclib
    palbociclib 125 mg capsule orally daily (for a 3 weeks on and 1 week off cycle for a total of 14 weeks from start of palbociclib) plus beginning 2 weeks after starting palbociclib, letrozole 2.5 mg tablet orally daily for a total of 12 weeks from start of letrozole therapy
    Interventions:
    • Drug: Letrozole
    • Drug: palbociclib
  • Experimental: D: letrozole + palbociclib
    letrozole 2.5 mg tablet orally daily for a total of 14 weeks plus palbociclib 125 mg capsule orally daily for a 3 weeks on and 1 week off cycle, for a total of 14 weeks from start of therapy
    Interventions:
    • Drug: Letrozole
    • Drug: palbociclib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: November 18, 2014)
306
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2019
Actual Primary Completion Date July 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study:Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02296801
Other Study ID Numbers  ICMJE NSABP FB-11
WI180455 ( Other Identifier: Pfizer )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party NSABP Foundation Inc
Study Sponsor  ICMJE NSABP Foundation Inc
Collaborators  ICMJE
  • Pfizer
  • Royal Marsden NHS Foundation Trust
  • Institute of Cancer Research, United Kingdom
Investigators  ICMJE
Principal Investigator:Norman Wolmark, MDNSABP Foundation Inc
PRS Account NSABP Foundation Inc
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP