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 | Completed Phase 2 Results DMC

• 2 other identifiers: NSABP FB-11WI180455
• Study Type: interventional
• Target: 307
• Locations: 3 countries
• Sites: 52

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.

Conditions

Breast Cancer; Breast Carcinoma; Breast Tumors

Outcome Measures

Primary Outcomes (2)

• Measurement of the Proliferation Marker Ki67 (% Positive Tumor Cells)

  The change in Ki67 from baseline to 14 weeks.

  Baseline and at 14 weeks

• Clinical Response : Number of Patients Who Have Resolution of Measurable Lesions or no New Lesions or Other Signs of Disease Progression Compared to Baseline.

  Clinical Response is assessed by ultrasound at the end of the treatment (week 14) according to ECOG response criteria defined in Appendix A1 of the protocol. Number of participants with clinical complete response.

  Baseline and at 14 weeks

Secondary Outcomes (5)

• Pathological Complete Response (pCR): Number of Patients With no Lesions in Breast and Nodes at Time of Surgery

  14 weeks

• Preoperative Endocrine Prognostic Index (PEPI) Score:

  14 weeks

• Number and Severity of Adverse Events

  Baseline and weekly through 12 months after randomization

• Measurement of Ki67 Marker

  Week 2 and week 14

• Comparison of Surgical Intent (Mastectomy; Breast Conservation)

  Time frame between baseline and surgery date. (Note-surgical intent happened before randomization).

Study Arms (5)

A: letrozole

ACTIVE COMPARATOR

letrozole 2.5 mg tablet orally daily for 14 weeks

Drug: Letrozole

B: letrozole then letrozole + palbociclib

EXPERIMENTAL

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

Drug: Letrozole; Drug: palbociclib

C: palbociclib then letrozole + palbociclib

EXPERIMENTAL

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

Drug: Letrozole; Drug: palbociclib

D: letrozole + palbociclib

EXPERIMENTAL

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

Drug: Letrozole; Drug: palbociclib

Combined Groups B+D+C

OTHER

Combined data

Drug: Letrozole; Drug: palbociclib

Interventions

Letrozole DRUG

A: letrozole; B: letrozole then letrozole + palbociclib; C: palbociclib then letrozole + palbociclib; Combined Groups B+D+C; D: letrozole + palbociclib

palbociclib DRUG

B: letrozole then letrozole + palbociclib; C: palbociclib then letrozole + palbociclib; Combined Groups B+D+C; D: letrozole + palbociclib

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• NSABP Foundation Inc: lead
• Pfizer: collaborator
• Royal Marsden NHS Foundation Trust: collaborator
• Institute of Cancer Research, United Kingdom: collaborator

Study Sites (52)

Long Beach Memorial Medical Center-Todd Cancer Institute

Long Beach, California, 90806, United States

Location

University of Miami Hospital and Clinics - Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Cancer Care Specialists of Central Illinois

Decatur, Illinois, 62526, United States

Location

Norton Healthcare Pavillion

Louisville, Kentucky, 40202, United States

Location

Norton Cancer Institute - Suburban, Norton Medical Plaza II

Louisville, Kentucky, 40207, United States

Location

Norton Cancer Institute - Brownsboro Medical Plaza I

Louisville, Kentucky, 40241, United States

Location

Metro-Minnesota CCOP

Saint Louis Park, Minnesota, 55416, United States

Location

Hope Women's Cancer Centers

Asheville, North Carolina, 28806, United States

Location

Providence Oncology and Hematology Clinic

Portland, Oregon, 97213, United States

Location

Pinnacle Health Ortenzio Cancer Center

Mechanicsburg, Pennsylvania, 17050, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15215, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15232, United States

Location

Women and Infants Hospital of Rhode Island

Providence, Rhode Island, 02905, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Joe Arrington Cancer Research and Treatment Center

Lubbock, Texas, 79410, United States

Location

Sentara Martha Jefferson Hospital-Phillips Family Cancer Center

Charlottesville, Virginia, 22911, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, H2W-1T8, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

McGill University Health Center

Montreal, Quebec, H4A 3J1, Canada

Location

CHU de Quebec - Universite Laval

Québec, Quebec, G1S 4L8, Canada

Location

Milton Keynes Hospital

Milton Keynes, Buckinghamshire, MK6 5LD, United Kingdom

Location

Hinchingbrooke Hospital

Huntingdon, Cambridgeshire, PE29 6NT, United Kingdom

Location

Royal Cornwall Hospital, Treliske

Truro, Cornwall, TR1 3LQ, United Kingdom

Location

Royal Devon and Exeter Hospital

Exeter, Devon, EX2 5DW, United Kingdom

Location

Royal Sussex County Hospital

Brighton, East Sussex, BN2 5BE, United Kingdom

Location

Southend Hospital

Westcliff-on-Sea, Essex, SS0 0RY, United Kingdom

Location

Darent Valley Hospital

Dartford, Kent, DA2 8DA, United Kingdom

Location

Maidstone Hospital

Maidstone, Kent, ME16 9QQ, United Kingdom

Location

Royal Liverpool University Hospital

Liverpool, Merseyside, L7 8XP, United Kingdom

Location

James Paget University Hospital

Great Yarmouth, Norfolk, NR31 6LA, United Kingdom

Location

Musgrove Park Hospital

Taunton, Somerset, TA1 5DA, United Kingdom

Location

Weston General Hospital

Weston-super-Mare, Somerset, BS23 4TQ, United Kingdom

Location

The Royal Marsden Hospital

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Salisbury Hospital

Salisbury, Wiltshire, SP2 8BJ, United Kingdom

Location

Kidderminster Hospital

Kidderminster, Worcestershire, DY11 6RJ, United Kingdom

Location

Alexandra Hospital

Redditch, Worcestershire, B98 7UB, United Kingdom

Location

Worcestershire Royal Hospital

Worcester, Worcestershire, WR5 1DD, United Kingdom

Location

Belfast City Hospital

Belfast, BT9 7AB, United Kingdom

Location

Royal Bournemouth Hospital

Bournemouth, BH7 7DW, United Kingdom

Location

Western General Hospital (Edinburgh Cancer Centre)

Edinburgh, EH4 2XU, United Kingdom

Location

St James' University Hospital

Leeds, LS9 7TF, United Kingdom

Location

Barnet Hospital

London, EN5 3DJ, United Kingdom

Location

Whittington Hospital

London, N19 5NF, United Kingdom

Location

University College London Hospitals

London, NW1 2BU, United Kingdom

Location

The Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

Charing Cross Hospital

London, W8 6RF, United Kingdom

Location

Nottingham University Hospitals NHS Trust, City Campus

Nottingham, NG5 1PB, United Kingdom

Location

Derriford Hospital

Plymouth, PL6 8DH, United Kingdom

Location

Singleton Hospital

Swansea, SA2 8QA, United Kingdom

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Letrozole; palbociclib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Director, Department of Site and Study Management
• Organization: NSABP Foundation Inc

industrytrials@nsabp.org

1-800-270-3165

Study Officials

• Norman Wolmark, MD

  NSABP Foundation Inc

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2014
• First Posted: November 20, 2014
• Study Start: January 1, 2015
• Primary Completion: July 1, 2018
• Study Completion: March 1, 2019
• Last Updated: January 13, 2022
• Results First Posted: January 13, 2022

Record last verified: 2021-12

Locations

US (19); GB (29); CA (4)