AzTrials
AzTrials

Breast Cancer RecurrentPhase 3POLARNCT03820830

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

A Phase 3 study testing Palbociclib 125mg and Standard endocrine therapy in people with Breast Cancer Recurrent, run by ETOP IBCSG Partners Foundation at 53 sites in 6 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer Recurrent
What is being tested?
Palbociclib 125mg and Standard endocrine therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
405 participants
Where
53 sitesin 6 countries
Study dates
27 Aug 2019to 1 Jan 2029
Phase
Phase 3
Are there results?
Not yet: the study is under way

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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
Show all 13Show fewer
  • 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
  • 8.-10. 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

Who cannot join

  • 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.
Show all 14Show fewer
  • 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
  • History of extensive disseminated/bilateral or known presence of interstitial fibrosis or interstitial lung disease, including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, obliterative bronchiolitis, and pulmonary fibrosis. A history of prior radiation pneumonitis is not considered an exclusion criterion.

Trial locations and contacts

53 sites in 6 countries.

53 sites in 6 countries

France14 sites

  • Institut Sainte Catherine

    Avignon, 84918

  • Institut Bergonie

    Bordeaux, 33076

  • Polyclinique Bordeaux Nord

    Bordeaux, 333000

  • Centre Francois Baclesse

    Caen, 14000

  • Cêntre Hospitaler de Cholet

    Cholet, 49300

  • Centre Georges François Leclerc

    Dijon, 21079

  • Centre Hospitalier Universitaire de Limoges

    Limoges, 87000

  • Groupe hospitalier de Bretagne Sud, Hôpital du Scorff

    Lorient

  • Centre Leon Berard

    Lyon, 69008

  • ICM Val d'Aurelle

    Montpellier, 34298

  • Centre Antoine Lacassagne

    Nice, 06189

  • Centre Paul Strauss

    Strasbourg

  • Institut Claudius Regaud

    Toulouse, 31100

  • Gustave Roussy

    Villejuif, 94800

Other trials in France

Spain14 sites

  • Hospital Universitario de La Coruña

    A Coruña

  • Hospital General Universitario de Alicante

    Alicante

  • Hospital Universitario Vall d´Hebrón

    Barcelona

  • Instituto Catalan de Oncologia L´Hospitalet

    Barcelona

  • Hospital de Basurto

    Bilbao

  • Institut Català d´Oncología (ICO)

    Girona

  • Hospital Universitario 12 de Octubre

    Madrid

  • HU Ramón y Cajal

    Madrid

  • Hospital Virgen de la Victoria

    Málaga

  • Hospital Universitario de Canarias

    San Cristóbal de La Laguna, Tenerife

  • Hospital Virgen de la Macarena

    Seville

  • Instituto Valenciano de Oncología (IVO)

    Valencia

  • Hospital Universitario Río Hortega

    Valladolid

  • Hospital Universitario Miguel Servet

    Zaragoza

Other trials in Spain

Italy10 sites

  • Cro Irccs

    Aviano

  • ASST Papa Giovanni XXIII

    Bergamo

  • PO Antonio Perrino Brindisi

    Brindisi

  • Istituto scientifico Romagnolo per lo studio e la cura

    Meldola

  • Istituto Europeo di Oncologia

    Milan

  • AOU Maggiore Della Carita, University of Eastern Piedmont

    Novara

  • Azienda Ospedaliero-Universitaria di Parma

    Parma

  • Istituti Clinici Scientifici Maugeri

    Pavia

  • Ospedale S. Stefano

    Prato

  • U.O. Oncologia, Ospedale Infermi

    Rimini

Other trials in Italy

Switzerland10 sites

  • Kantonsspital Baden

    Baden

  • Brustzentrum Basel Bethesda Spital

    Basel

  • Inselspital Bern

    Bern

  • Centre du Sein Fribourg

    Fribourg

  • Fondazione Oncologia Lago Maggiore

    Locarno

  • Kouros Moccia Oncologia

    Locarno

  • Luzerner Kantonsspital

    Lucerne

  • Kantonsspital Winterthur

    Winterthur

  • BZ Bethanien

    Zurich, 8001

  • Brust-Zentrum AG Zürich

    Zurich

Other trials in Switzerland

Austria4 sites

  • Medizinische Universität Graz (MUG)

    Graz

  • Medizinische Universität Innsbruck - Univ.-Klinik f. Frauenheilkunde

    Innsbruck

  • Uniklinikum Salzburg

    Salzburg

  • MUW - Universitätsklinik für Innere Medizin

    Vienna

Other trials in Austria

Hungary1 site

  • National Institute of Oncology

    Budapest

Other trials in Hungary

About this study

Official title: A Phase III Open-label, Multicenter, Randomized Trial of Adjuvant Palbociclib in Combination With Endocrine Therapy Versus Endocrine Therapy Alone for Patients With Hormone Receptor Positive / HER2-negative Resected Isolated Locoregional Recurrence of Breast Cancer

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.

Read more

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.

Read the detailed description

Local or regional recurrence of breast cancer after mastectomy or lumpectomy indicates a poor prognosis, and accompanies or precedes distant metastasis in a high proportion of patients. Patients with isolated locoregional recurrences (ILRR), without evidence of distant metastasis hold a substantial risk of developing subsequent distant metastasis, with 5-year survival probabilities ranging between 45% and 80% after locoregional recurrence. These outcomes show the powerful negative prognostic importance of ILRR events and the need for treatments beyond surgical removal of the ILRR.

Adjuvant chemotherapy and endocrine therapies reduce the risk of relapse and death in patients with primary breast cancer. However, few data are available to inform the recommendation of systemic treatment for locoregional recurrence.

The International Breast Cancer Studies Group carried out the CALOR trial, Chemotherapy as Adjuvant for Locally Recurrent breast cancer (IBCSG 27-02 / BIG 1-02 / NSABP B-37), in collaboration with the Breast International Group (BIG) and the National Surgical Adjuvant Breast and Bowel Project (NSABP), to establish whether chemotherapy improves the outcome of patients with ILRR. An updated, final analysis of CALOR after median follow-up of about 9 years was published in the Journal of Clinical Oncology in April 2018, which confirmed chemotherapy benefitted patients with resected ER-negative ILRR and did not support the use of chemotherapy for ER-positive ILRR.

CALOR results strongly suggest that tailoring treatment according to the disease characteristics of the recurrent lesion, in this case ILRR, provides a better indication of the possible responsiveness to treatment than relying on the characteristics of the primary tumor.

Palbociclib has been granted FDA approval in the U.S. for the treatment of HR-positive/HER2-negative advanced breast cancer in combination with the hormonal treatments letrozole and fulvestrant given the unprecedented results in terms of efficacy of two pivotal clinical trials (PALOMA-2 and PALOMA-3). Palbociclib and other CDK4/6 inhibitors have also shown a good toxicity profile and therefore are ideal candidates for combination with hormonal therapy. CDK4/6 pathway activation is a well-known mechanism of resistance to endocrine therapy, indeed CDK4/6 inhibitors have shown activity in cellular models of acquired resistance to endocrine therapies.

The reason for prolonged duration of palbociclib in the adjuvant setting (2 years) comes from the evidence of preclinical studies where cell senescence was investigated as an appealing mechanism of cell death and was indeed observed in vitro after exposure of breast cancer cells and tumors to a combination of endocrine therapy and palbociclib. It is therefore hypothesized that the longer patients receive combined treatment with palbociclib and an antiestrogen, the more likely they may derive prolonged clinical benefit.

Based on the results of the CALOR trial and on strong evidence of activity of the combination of CDK4/6 inhibitors and endocrine therapy, the hypothesis of the POLAR trial is that the CDK4/6 inhibitor palbociclib in combination with endocrine therapy may be active as adjuvant therapy in patients with HR-positive/HER2-negative resected isolated locoregional recurrence of breast cancer.

Being tested
Palbociclib 125mg, Standard endocrine therapy
Keywords
hormone receptor positive breast cancer, HER2 receptor negative, CDK4/6 inhibitor

What participants receive

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

  • Palbociclib 125mgDrug

    Also called Ibrance, PD-0332991

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

  • Standard endocrine therapyDrug

    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.

Study groups in NCT03820830
Study groupRoleWhat they receive
Palbociclib plus standard endocrine therapyExperimentalPalbociclib 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.
Receives: Drug: Palbociclib 125mg; Drug: Standard endocrine therapy
Standard endocrine therapyActive comparatorAromatase 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.
Receives: Drug: Standard endocrine therapy

What is being measured

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

  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.

    Measured: 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)

  1. Number of participants with treatment related adverse events.

    Adverse events, defined as any untoward medical occurrence, will be collected using CTCAE v5. All grades for targeted adverse events will be collected and all grades ≥3 for non-targeted adverse events. The maximum grade of each targeted adverse event during the protocol treatment phase will be determined, the frequencies summarized and tabulated according to grade and treatment assignment.

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

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

    Defined as the time from randomization until the date of first documented appearance of invasive local, regional or distant recurrence (including ipsilateral tumour recurrence), or invasive contralateral breast cancer.

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

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

    Defined as the time from randomization until the date of first documented distant recurrence of breast cancer.

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

  4. Duration of overall survival of all randomized participants.

    Defined as the time from randomization until death from any cause.

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

Timeline

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

  1. First posted29 Jan 2019
  2. Study start27 Aug 2019
  3. Primary completionDec 2026 (estimated)
  4. Study completion1 Jan 2029 (estimated)

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
405 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03820830
Sponsor's protocol ID
IBCSG 59-19
Other IDs
2018-003553-19, BIG 18-02, WI239003, 2018
Acronym
POLAR
Status last verified
Sep 2026
First submitted
25 Jan 2019
Last updated
3 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 19349544

  • 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.

    PubMed 18650162

  • 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.

    PubMed 7931476

  • 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.

    PubMed 24439313

  • 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.

    PubMed 29443653

  • 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.

    PubMed 25188473

  • 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.

    PubMed 25991817

  • 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.

    PubMed 25524798

  • 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.

    PubMed 26488700

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Palbociclib 125mg and Standard endocrine therapy in people with Breast Cancer Recurrent, run by ETOP IBCSG Partners Foundation at 53 sites in 6 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 13 inclusion and 14 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: under way, not looking for participants, as of the sponsor's last update on 3 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 53 sites in France, Spain, Italy, Switzerland, Austria and 1 more country. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Duration of invasive disease free survival of all randomized participants. (time frame: 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.). 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 NCT03820830, which also lists 9 linked publications.

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 3 Sep 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in