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Breast CancerPhase 2PALLETNCT02296801

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

A Phase 2 study testing Letrozole and palbociclib in people with Breast Cancer and Breast Carcinoma, run by NSABP Foundation Inc at 52 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer, Breast Carcinoma, Breast Tumors
What is being tested?
Letrozole and palbociclib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
307 participants
Where
52 sitesin 3 countries
Study dates
Jan 2015to Mar 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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).

Who cannot join

  • 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)
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  • 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.

Trial locations and contacts

52 sites in 3 countries.

52 sites in 3 countries

United Kingdom29 sites

  • Belfast City Hospital

    Belfast, BT9 7AB

  • Royal Bournemouth Hospital

    Bournemouth, BH7 7DW

  • Royal Sussex County Hospital

    Brighton, East Sussex, BN2 5BE

  • Darent Valley Hospital

    Dartford, Kent, DA2 8DA

  • Western General Hospital (Edinburgh Cancer Centre)

    Edinburgh, EH4 2XU

  • Royal Devon and Exeter Hospital

    Exeter, Devon, EX2 5DW

  • James Paget University Hospital

    Great Yarmouth, Norfolk, NR31 6LA

  • Hinchingbrooke Hospital

    Huntingdon, Cambridgeshire, PE29 6NT

  • Kidderminster Hospital

    Kidderminster, Worcestershire, DY11 6RJ

  • St James' University Hospital

    Leeds, LS9 7TF

  • Royal Liverpool University Hospital

    Liverpool, Merseyside, L7 8XP

  • Barnet Hospital

    London, EN5 3DJ

  • Whittington Hospital

    London, N19 5NF

  • University College London Hospitals

    London, NW1 2BU

  • The Royal Marsden Hospital

    London, SW3 6JJ

  • Charing Cross Hospital

    London, W8 6RF

  • Maidstone Hospital

    Maidstone, Kent, ME16 9QQ

  • Milton Keynes Hospital

    Milton Keynes, Buckinghamshire, MK6 5LD

  • Nottingham University Hospitals NHS Trust, City Campus

    Nottingham, NG5 1PB

  • Derriford Hospital

    Plymouth, PL6 8DH

  • Alexandra Hospital

    Redditch, Worcestershire, B98 7UB

  • Salisbury Hospital

    Salisbury, Wiltshire, SP2 8BJ

  • The Royal Marsden Hospital

    Sutton, Surrey, SM2 5PT

  • Singleton Hospital

    Swansea, SA2 8QA

  • Musgrove Park Hospital

    Taunton, Somerset, TA1 5DA

  • Royal Cornwall Hospital, Treliske

    Truro, Cornwall, TR1 3LQ

  • Southend Hospital

    Westcliff-on-Sea, Essex, SS0 0RY

  • Weston General Hospital

    Weston-super-Mare, Somerset, BS23 4TQ

  • Worcestershire Royal Hospital

    Worcester, Worcestershire, WR5 1DD

Other trials in United Kingdom

United States19 sites

  • Hope Women's Cancer Centers

    Asheville, North Carolina, 28806

  • Sentara Martha Jefferson Hospital-Phillips Family Cancer Center

    Charlottesville, Virginia, 22911

  • Cancer Care Specialists of Central Illinois

    Decatur, Illinois, 62526

  • Baylor College of Medicine

    Houston, Texas, 77030

  • Long Beach Memorial Medical Center-Todd Cancer Institute

    Long Beach, California, 90806

  • Norton Healthcare Pavillion

    Louisville, Kentucky, 40202

  • Norton Cancer Institute - Suburban, Norton Medical Plaza II

    Louisville, Kentucky, 40207

  • Norton Cancer Institute - Brownsboro Medical Plaza I

    Louisville, Kentucky, 40241

  • Joe Arrington Cancer Research and Treatment Center

    Lubbock, Texas, 79410

  • Pinnacle Health Ortenzio Cancer Center

    Mechanicsburg, Pennsylvania, 17050

  • University of Miami Hospital and Clinics - Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

  • West Virginia University

    Morgantown, West Virginia, 26506

  • Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15215

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15232

  • Providence Oncology and Hematology Clinic

    Portland, Oregon, 97213

  • Women and Infants Hospital of Rhode Island

    Providence, Rhode Island, 02905

  • Virginia Commonwealth University

    Richmond, Virginia, 23298

  • Metro-Minnesota CCOP

    Saint Louis Park, Minnesota, 55416

  • Swedish Cancer Institute

    Seattle, Washington, 98104

Other trials in United States

Canada4 sites

  • Centre Hospitalier de l'Universite de Montreal

    Montreal, Quebec, H2W-1T8

  • Jewish General Hospital

    Montreal, Quebec, H3T 1E2

  • McGill University Health Center

    Montreal, Quebec, H4A 3J1

  • CHU de Quebec - Universite Laval

    Québec, Quebec, G1S 4L8

Other trials in Canada

About this study

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.

Read the 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).

Being tested
Letrozole, palbociclib
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02296801
Study groupRoleWhat they receive
A: letrozoleActive comparatorletrozole 2.5 mg tablet orally daily for 14 weeks
Receives: Drug: Letrozole
B: letrozole then letrozole + palbociclibExperimentalletrozole 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
Receives: Drug: Letrozole; Drug: palbociclib
C: palbociclib then letrozole + palbociclibExperimentalpalbociclib 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
Receives: Drug: Letrozole; Drug: palbociclib
D: letrozole + palbociclibExperimentalletrozole 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
Receives: Drug: Letrozole; Drug: palbociclib
Combined Groups B+D+COtherCombined data
Receives: Drug: Letrozole; Drug: palbociclib

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    The change in Ki67 from baseline to 14 weeks.

    Measured: Baseline and at 14 weeks

  2. 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.

    Measured: Baseline and at 14 weeks

Secondary outcomes (5)

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

    Pathologic complete response in the breast (pCR breast) is defined as no histologic evidence of invasive tumour cells in the surgical breast specimen. Pathologic complete response in breast and axillary lymph nodes as well as non-axillary SN (pCR breast \& nodes) is defined as no histologic evidence of invasive tumour cells in the surgical breast specimen, axillary nodes, or SNs identified after neoadjuvant treatment. Data shows the pCR rates by randomised group.

    Measured: 14 weeks

  2. Preoperative Endocrine Prognostic Index (PEPI) Score:

    The PEPI score estimates the risk of cancer recurrence after treatment. Analysis of the PEPI score were pre-specified in the protocol and statistical analysis plan. However, pathological/biomarker characteristics which comprise this score such as the Allred score for ER status were not collected during the trial so cannot be calculated at this stage. PEPI Scale range is 0-16 for RFS. Higher score represents worse outcome. No combination of subscales.

    Measured: 14 weeks

  3. Number and Severity of Adverse Events

    To evaluate the overall safety and tolerability for the combination of letrozole and palbociclib. The number of patients experiencing at least one adverse event. Refer to Adverse Events section for more details.

    Measured: Baseline and weekly through 12 months after randomization

  4. Measurement of Ki67 Marker

    To compare Ki67 results after 2 weeks and 14 weeks of study therapy. Log fold change in Ki67 from week 2-week 14.

    Measured: Week 2 and week 14

  5. Comparison of Surgical Intent (Mastectomy; Breast Conservation)

    To compare changes between surgical intent at baseline; surgical intent after 14 weeks; and actual surgery received after treatment with letrozole with or without palbociclib. Percentage of patients change to receiving breast conservation and receiving breast conservation.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Nov 2014 (estimated)
  2. Study startJan 2015
  3. Primary completionJul 2018
  4. Study completionMar 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
307 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02296801
Sponsor's protocol ID
NSABP FB-11
Other IDs
WI180455
Acronym
PALLET
Status last verified
Dec 2021
First submitted
18 Nov 2014
Last updated
13 Jan 2022
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Letrozole and palbociclib in people with Breast Cancer and Breast Carcinoma, run by NSABP Foundation Inc at 52 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 52 sites in United Kingdom, United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Jan 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Measurement of the Proliferation Marker Ki67 (% Positive Tumor Cells) (time frame: Baseline and at 14 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02296801.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2022.

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PALLET Clinical Trial NCT02296801 | AzTrials