Palbociclib for HR Positive / HER2-negative Isolated Locoregional Recurrence of Breast Cancer

NCT03820830 | Active Not Recruiting Phase 3 DMC

• 4 other identifiers: IBCSG 59-192018-003553-19BIG 18-02WI239003
• Study Type: interventional
• Target: 405
• Locations: 6 countries
• Sites: 53

Brief Summary

POLAR is a phase III clinical trial, which will test the safety and efficacy of an investigational combination of drugs to learn whether the combination of drugs works for a specific cancer. Palbociclib (Ibrance®) is the name of the investigational agent, which is assessed together with standard anti-hormone therapy in this study. Palbociclib is used to treat patients with hormone receptor-positive / HER2-negative breast cancer which has spread beyond the original tumor and/or to other organs. During this study, anti-hormone therapy will consist of either a selective estrogen receptor modulator (such as tamoxifen) or an aromatase inhibitor (anastrozole, letrozole, exemestane) or fulvestrant (Faslodex®). Premenopausal women and men may also receive a drug called an LHRH (luteinizing hormone-releasing hormone) agonist by injection. It is standard of care for people with hormone receptor positive breast cancer to take anti-hormone therapy. The study doctor will determine the type of standard anti-hormone therapy that will be given during this trial. The purpose of the POLAR study is to compare the effect of using 3 years of palbociclib in combination with standard anti-hormone therapy with standard anti-hormone therapy alone and to evaluate the time until the breast cancer returns, if it does return.

Conditions

Breast Cancer Recurrent

Keywords

hormone receptor positive breast cancer; HER2 receptor negative; CDK4/6 inhibitor

Outcome Measures

Primary Outcomes (1)

• Duration of invasive disease free survival of all randomized participants.

  Defined as the time from randomization until first appearance of invasive local, regional or distant recurrence (including invasive ipsilateral breast tumour recurrence), invasive contralateral breast cancer, a second (non-breast) invasive cancer, or death from any cause. The sites of first invasive disease events will be compared between treatment groups using a stratified log-rank test and will be tabulated.

  Assessed from the date treatment starts until the date of first documented invasive local, regional or distant recurrence, a second invasive cancer or death, or until approximately 4 years after treatment stops.

Secondary Outcomes (4)

• Number of participants with treatment related adverse events.

  Adverse events will be collected from the date consent is signed, and during treatment until 30-60 days after treatment stops.

• Duration of breast cancer free interval of all randomized participants.

  Assessed from the date of randomization until the date of first documented breast cancer recurrence, or until approximately 4 years after treatment stops.

• Duration of distant recurrence free interval of all randomized participants.

  Assessed from the date of randomization until the date of first documented distant disease progression, or until approximately 4 years after treatment stops.

• Duration of overall survival of all randomized participants.

  Assessed from the date of randomization until approximately 4 years after treatment stops, or until the date of death from any cause.

Study Arms (2)

Palbociclib plus standard endocrine therapy

EXPERIMENTAL

Palbociclib 125 mg/day tablet taken orally for 21 days, followed by 7 days rest for 3 years from randomization, plus standard endocrine therapy for at least 3 years from randomization.

Drug: Palbociclib 125mg; Drug: Standard endocrine therapy

Standard endocrine therapy

ACTIVE COMPARATOR

Aromatase inhibitor (anastrozole or exemestane or letrozole) oral daily tablet, or Selective Estrogen Receptor Modulator (SERM) such as tamoxifen oral daily tablet or fulvestrant (Faslodex) injection once every 2 weeks for 3 doses then every month. Premenopausal women and men may also receive an LHRH (luteinizing hormone-releasing hormone) agonist by injection. Standard endocrine therapy will be given for at least 3 years from randomization.

Drug: Standard endocrine therapy

Interventions

Palbociclib 125mg DRUG

Palbociclib 125 mg oral tablet taken daily for 3 years from randomization

Also known as: Ibrance, PD-0332991

Palbociclib plus standard endocrine therapy

Standard endocrine therapy DRUG

Aromatase inhibitor (anastrozole or exemestane or letrozole) oral daily tablet, or Selective Estrogen Receptor Modulator (SERM) such as tamoxifen oral daily tablet or fulvestrant (Faslodex) injection once every 2 weeks for 3 doses then every month. Premenopausal women and men may also receive an LHRH (luteinizing hormone-releasing hormone) agonist by injection. Standard endocrine therapy will be given for at least 3 years from randomization.

Palbociclib plus standard endocrine therapy; Standard endocrine therapy

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed invasive breast cancer, defined as first proven ipsilateral local and/or regional recurrence of a primary invasive breast cancer in at least one of these sites:
• breast;
• the chest wall including mastectomy scar and/or skin;
• axillary or internal mammary lymph nodes.
• Completion of locoregional therapy:
• completion of gross excision of recurrence within 6 months prior to randomization;
• completion of radiotherapy (if given) more than 2 weeks prior to randomization
• Negative or microscopically involved margins
• Female or male aged 18 years or older
• ECOG performance status 0 or 1
• Recurrent tumor must be hormone receptor positive: ER+ and/or PgR+ ≥1% by IHC
• Recurrent tumor must be HER2-negative (0, 1+, 2+ by IHC and/or ISH/FISH not amplified).Tumor with HER2 status 2+ by IHC must also be negative (not amplified) by ISH/FISH
• Normal hematological, renal, and liver function 11. The patient agrees to make tumor (diagnostic core biopsy or surgical specimen of ipsilateral isolated locoregional recurrence) available for submission for central pathology review 12. Patients must either be planned to initiate, or have already started, endocrine therapy for ipsilateral isolated locoregional recurrence 13.) Written Informed Consent prior to randomization

You may not qualify if:

• Recurrence of any size with direct extension to the chest wall and/or to the skin (ulceration or skin nodules) not surgically removable
• Evidence of distant metastasis as based on conventional staging examinations (physical, chest X-ray or CT, abdominal ultrasound or CT, bone scintigraphy or FDG-PET-CT).
• Bilateral synchronous or metachronous invasive breast cancer (in situ carcinoma of the contralateral breast is allowed)
• Inflammatory breast cancer
• Patients with a history of malignancy, other than invasive breast cancer, with the following exceptions:
• Patients diagnosed, treated and disease-free for at least 5 years and deemed by the investigator to be at low risk for recurrence of that malignancy are eligible.
• Patients with the following malignancies are eligible, even if diagnosed and treated within the past 5 years: ductal carcinoma in situ of the breast; cervical cancer in situ; thyroid cancer in situ; non-metastatic, non-melanomatous skin cancers.
• Previous treatment with palbociclib or any other CDK 4/6 inhibitors
• Previous or planned chemotherapy or planned radiotherapy for the ipsilateral isolated locoregional recurrence (radiotherapy is allowed, but must be completed more than 2 weeks prior to randomization)
• Concurrent disease or condition that would make the patient inappropriate for study participation or any serious medical disorder that would interfere with the patient's safety
• Pregnant or lactating women; lactation has to stop before randomization
• Patients with psychiatric illness/social situations that would limit compliance with study requirements
• Contraindications or known hypersensitivity to the palbociclib or excipients

Sponsors & Collaborators

• ETOP IBCSG Partners Foundation: lead
• Pfizer: collaborator

Study Sites (53)

Medizinische Universität Graz (MUG)

Graz, Austria

Location

Medizinische Universität Innsbruck - Univ.-Klinik f. Frauenheilkunde

Innsbruck, Austria

Location

Uniklinikum Salzburg

Salzburg, Austria

Location

MUW - Universitätsklinik für Innere Medizin

Vienna, Austria

Location

Institut Sainte Catherine

Avignon, 84918, France

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Polyclinique Bordeaux Nord

Bordeaux, 333000, France

Location

Centre Francois Baclesse

Caen, 14000, France

Location

Cêntre Hospitaler de Cholet

Cholet, 49300, France

Location

Centre Georges François Leclerc

Dijon, 21079, France

Location

Centre Hospitalier Universitaire de Limoges

Limoges, 87000, France

Location

Groupe hospitalier de Bretagne Sud, Hôpital du Scorff

Lorient, France

Location

Centre Leon Berard

Lyon, 69008, France

Location

ICM Val d'Aurelle

Montpellier, 34298, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Centre Paul Strauss

Strasbourg, France

Location

Institut Claudius Regaud

Toulouse, 31100, France

Location

Gustave Roussy

Villejuif, 94800, France

Location

National Institute of Oncology

Budapest, Hungary

Location

Cro Irccs

Aviano, Italy

Location

ASST Papa Giovanni XXIII

Bergamo, Italy

Location

PO Antonio Perrino Brindisi

Brindisi, Italy

Location

Istituto scientifico Romagnolo per lo studio e la cura

Meldola, Italy

Location

Istituto Europeo di Oncologia

Milan, Italy

Location

AOU Maggiore Della Carita, University of Eastern Piedmont

Novara, Italy

Location

Azienda Ospedaliero-Universitaria di Parma

Parma, Italy

Location

Istituti Clinici Scientifici Maugeri

Pavia, Italy

Location

Ospedale S. Stefano

Prato, Italy

Location

U.O. Oncologia, Ospedale Infermi

Rimini, Italy

Location

Hospital Universitario de Canarias

San Cristóbal de La Laguna, Tenerife, Spain

Location

Hospital Universitario de La Coruña

A Coruña, Spain

Location

Hospital General Universitario de Alicante

Alicante, Spain

Location

Hospital Universitario Vall d´Hebrón

Barcelona, Spain

Location

Instituto Catalan de Oncologia L´Hospitalet

Barcelona, Spain

Location

Hospital de Basurto

Bilbao, Spain

Location

Institut Català d´Oncología (ICO)

Girona, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

HU Ramón y Cajal

Madrid, Spain

Location

Hospital Virgen de la Victoria

Málaga, Spain

Location

Hospital Virgen de la Macarena

Seville, Spain

Location

Instituto Valenciano de Oncología (IVO)

Valencia, Spain

Location

Hospital Universitario Río Hortega

Valladolid, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, Spain

Location

Kantonsspital Baden

Baden, Switzerland

Location

Brustzentrum Basel Bethesda Spital

Basel, Switzerland

Location

Inselspital Bern

Bern, Switzerland

Location

Centre du Sein Fribourg

Fribourg, Switzerland

Location

Fondazione Oncologia Lago Maggiore

Locarno, Switzerland

Location

Kouros Moccia Oncologia

Locarno, Switzerland

Location

Luzerner Kantonsspital

Lucerne, Switzerland

Location

Kantonsspital Winterthur

Winterthur, Switzerland

Location

BZ Bethanien

Zurich, 8001, Switzerland

Location

Brust-Zentrum AG Zürich

Zurich, Switzerland

Location

Related Publications (9)

• Anderson SJ, Wapnir I, Dignam JJ, Fisher B, Mamounas EP, Jeong JH, Geyer CE Jr, Wickerham DL, Costantino JP, Wolmark N. Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in patients treated by breast-conserving therapy in five National Surgical Adjuvant Breast and Bowel Project protocols of node-negative breast cancer. J Clin Oncol. 2009 May 20;27(15):2466-73. doi: 10.1200/JCO.2008.19.8424. Epub 2009 Apr 6.

  PMID: 19349544 BACKGROUND

• Wapnir IL, Aebi S, Geyer CE, Zahrieh D, Gelber RD, Anderson SJ, Robidoux A, Bernhard J, Maibach R, Castiglione-Gertsch M, Coates AS, Piccart MJ, Clemons MJ, Costantino JP, Wolmark N; IBCSG; BIG; NSABP. A randomized clinical trial of adjuvant chemotherapy for radically resected locoregional relapse of breast cancer: IBCSG 27-02, BIG 1-02, and NSABP B-37. Clin Breast Cancer. 2008 Jun;8(3):287-92. doi: 10.3816/CBC.2008.n.035.

  PMID: 18650162 BACKGROUND

• Borner M, Bacchi M, Goldhirsch A, Greiner R, Harder F, Castiglione M, Jungi WF, Thurlimann B, Cavalli F, Obrecht JP, et al. First isolated locoregional recurrence following mastectomy for breast cancer: results of a phase III multicenter study comparing systemic treatment with observation after excision and radiation. Swiss Group for Clinical Cancer Research. J Clin Oncol. 1994 Oct;12(10):2071-7. doi: 10.1200/JCO.1994.12.10.2071.

  PMID: 7931476 BACKGROUND

• Aebi S, Gelber S, Anderson SJ, Lang I, Robidoux A, Martin M, Nortier JW, Paterson AH, Rimawi MF, Canada JM, Thurlimann B, Murray E, Mamounas EP, Geyer CE Jr, Price KN, Coates AS, Gelber RD, Rastogi P, Wolmark N, Wapnir IL; CALOR investigators. Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR): a randomised trial. Lancet Oncol. 2014 Feb;15(2):156-63. doi: 10.1016/S1470-2045(13)70589-8. Epub 2014 Jan 16.

  PMID: 24439313 BACKGROUND

• Wapnir IL, Price KN, Anderson SJ, Robidoux A, Martin M, Nortier JWR, Paterson AHG, Rimawi MF, Lang I, Baena-Canada JM, Thurlimann B, Mamounas EP, Geyer CE Jr, Gelber S, Coates AS, Gelber RD, Rastogi P, Regan MM, Wolmark N, Aebi S; International Breast Cancer Study Group; NRG Oncology, GEICAM Spanish Breast Cancer Group, BOOG Dutch Breast Cancer Trialists' Group; Breast International Group. Efficacy of Chemotherapy for ER-Negative and ER-Positive Isolated Locoregional Recurrence of Breast Cancer: Final Analysis of the CALOR Trial. J Clin Oncol. 2018 Apr 10;36(11):1073-1079. doi: 10.1200/JCO.2017.76.5719. Epub 2018 Feb 14.

  PMID: 29443653 BACKGROUND

• Migliaccio I, Di Leo A, Malorni L. Cyclin-dependent kinase 4/6 inhibitors in breast cancer therapy. Curr Opin Oncol. 2014 Nov;26(6):568-75. doi: 10.1097/CCO.0000000000000129.

  PMID: 25188473 BACKGROUND

• Wardell SE, Ellis MJ, Alley HM, Eisele K, VanArsdale T, Dann SG, Arndt KT, Primeau T, Griffin E, Shao J, Crowder R, Lai JP, Norris JD, McDonnell DP, Li S. Efficacy of SERD/SERM Hybrid-CDK4/6 Inhibitor Combinations in Models of Endocrine Therapy-Resistant Breast Cancer. Clin Cancer Res. 2015 Nov 15;21(22):5121-5130. doi: 10.1158/1078-0432.CCR-15-0360. Epub 2015 May 19.

  PMID: 25991817 BACKGROUND

• Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, Ettl J, Patel R, Pinter T, Schmidt M, Shparyk Y, Thummala AR, Voytko NL, Fowst C, Huang X, Kim ST, Randolph S, Slamon DJ. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015 Jan;16(1):25-35. doi: 10.1016/S1470-2045(14)71159-3. Epub 2014 Dec 16.

  PMID: 25524798 BACKGROUND

• Turner NC, Huang Bartlett C, Cristofanilli M. Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2015 Oct 22;373(17):1672-3. doi: 10.1056/NEJMc1510345. No abstract available.

  PMID: 26488700 BACKGROUND

MeSH Terms

Interventions

palbociclib

Study Officials

• Elisabetta Munzone, MD

  European Institute of Oncology

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2019
• First Posted: January 29, 2019
• Study Start: August 27, 2019
• Primary Completion (Estimated): July 27, 2026
• Study Completion (Estimated): January 1, 2029
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (4); CH (10); HU (1); IT (10); ES (14); FR (14)