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Breast NeoplasmsPhase 2NA-PHER2NCT02530424

"Neo-Adjuvant Treatment With Palbociclib: Effect on Ki67 and Apoptosis Before, During and After Treatment "

A Phase 2 study testing Trastuzumab, Pertuzumab and Palbociclib in people with Breast Neoplasms, run by Fondazione Michelangelo at 7 sites in Italy.

Completed

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

Official record
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Trial summary

This is a multicenter neoadjuvant trial conducted under the sponsorship and overall trial management of the Fondazione Michelangelo in Italy. Women with a diagnosis of invasive unilateral non metastatic ER-positive breast cancer expressing HER2 and suitable for neoadjuvant therapy Patients in this study will receive… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Neoplasms
What is being tested?
Trastuzumab, Pertuzumab and Palbociclib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
102 participants
Where
7 sitesItaly
Study dates
May 2015to Nov 2019
Phase
Phase 2
Are there results?
None posted in the registry

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

  • Female patients aged 18 years or older with tumors suitable for neoadjuvant treatment
  • Early (> 1.5 cm) or locally advanced untreated breast cancer
  • Histologically confirmed invasive unilateral breast cancer
  • HER2 status to be centrally confirmed (HER2 3+ of neu amplified for cohorts A and B; HER2 1+/2+ without amplification for cohort C)
  • Positive estrogen receptor (ER) > 10% and known progesterone receptor (PgR). Note: PgR assessment must be positive for cohort C
  • Ki67 > 20% for cohort C
Show all 11Show fewer
  • Available paraffin-embedded tumor block taken at diagnostic biopsy for central retrospective confirmation of HER2 and ER eligibility and for assessment of Ki67 value and apoptosis is mandatory
  • All patients must agree to provide tumor tissues for centralized assessment of KI67 values and apoptosis at the required timelines (2 weeks from starting protocol therapy and at surgery)
  • ECOG (Eastern Cooperative Oncology Group) performance status 0 or 1
  • Written informed consent to participate in the trial (approved by the Institutional Review Board/ Independent Ethics Committee) obtained prior to any study specific screening procedures
  • Willing and able to comply with the protocol

Who cannot join

  • Evidence of bilateral invasive breast cancer or metastatic disease (M1)
  • Pregnant or lactating women.
  • Women with childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception
  • Previous treatment with chemotherapy, hormonal therapy or an investigational drug for any type of malignancy
  • Previous extensive radiotherapy
  • Previous investigational treatment for any condition within 4 weeks of registration date
Show all 17Show fewer
  • Known hypersensitivity reaction to one of the compounds or incorporated substances used in this protocol
  • Previous or concomitant malignancy of any other type that could affect compliance with the protocol or interpretation of results.
  • Other serious illness or medical condition including: history of documented congestive cardiac failure; angina pectoris requiring anti-anginal medication; evidence of transmural infarction on ECG; poorly controlled hypertension; clinically significant valvular heart disease; high-risk uncontrolled arrhythmias
  • Baseline left ventricular ejection fraction (LVEF) < 55% by echocardiography or multi-gated scintigraphic scan (MUGA)
  • QTc (corrected QT interval) >480 msec or a family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes (TdP)
  • Patients with a history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant and precluding informed consent or adversely affecting compliance with study drugs
  • Serious uncontrolled infections (bacterial or viral) or poorly controlled diabetes mellitus
  • Current use or anticipated need for food or drugs that are known strong CYP3A4 (cytochrome P450 3A4) inhibitors or inducers
  • Uncontrolled electrolyte disorders that can compound the effects of a QTc prolonging drug (e.g., hypocalcemia, hypokalemia, hypomagnesemia)
  • Abnormal baseline hematological values:
  • Abnormal baseline liver function, bilirubin, creatinine and/or INR (international normalized ratio)

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

Italy7 sites

  • Policlinico Sant'Orsola Malpighi

    Bologna, BO, 40138

  • Azienda Ospedaliero Universitaria di Ferrara - Arcispedale S. Anna

    Ferrara, FE, 44124

  • IST San Martino

    Genova, GE, 16132

  • Ospedale San Raffaele

    Milan, MI, 20100

  • Istituto Europeo di Oncologia

    Milan, MI, 20141

  • Arcispedale S.Maria Nuova A.O.Reggio Emilia

    Reggio Emilia, RE, 42123

  • Ospedale Santa Maria della Misericordia

    Udine, UD, 33100

Other trials in Italy

About this study

Official title: "Neo-Adjuvant Treatment With the CDK4,6 Inhibitor Palbociclib in HER2-positive and ER-positive Breast Cancer: Effect on Ki67 and Apoptosis Before, During and After Treatment "

This is a multicenter neoadjuvant trial conducted under the sponsorship and overall trial management of the Fondazione Michelangelo in Italy.

Women with a diagnosis of invasive unilateral non metastatic ER-positive breast cancer expressing HER2 and suitable for neoadjuvant therapy Patients in this study will receive: Trastuzumab+Pertuzumab+Palbociclib with or without Fulvestrant (HPPF)

Read more

Trastuzumab 8 mg/kg loading dose IV, then 6 mg/kg IV q.3 wks (repeat for a total of 6 administrations) Pertuzumab 840 mg loading dose IV, then 420 mg IV q. 3 wks (repeat for a total of 6 administrations) Palbociclib 125 mg po q.d. x 21 q. 4 wks (= 1 cycle; repeat for a total of 5 cycles) Fulvestrant will be given intra-muscle at the dose of 500 mg every 4 weeks (repeat for 5 times) with an additional 500 mg dose given two weeks after the initial dose (total administrations including the additional one = 6)

The total duration of neoadjuvant palbociclib (5 cycles every 4 weeks) and fulvestrant (5 administrations every 4 weeks plus the additional dose given two weeks after the initial dose) was selected to match as closely as possible the total duration of the six planned 3-weekly administrations of trastuzumab and pertuzumab

Definitive surgery will be performed not earlier than 14 days and not later than 28 days after the last dose of any of the drugs in the combination reported above

After completion of the neoadjuvant and surgical treatment patients will receive irradiation as locally acceptable.

Patients will also continue to receive systemic drug therapy including chemotherapy (plus standard anti-HER2 treatment until completion of full 1 year if HER2 3+ or neu amplified, i.e. cohorts A and B) and endocrine therapy according to local guidelines at the Investigator's discretion.

Read the detailed description

This is a multicenter neoadjuvant trial conducted under the sponsorship and overall trial management of the Fondazione Michelangelo in Italy.

Three cohorts of patients are planned

Patients with ER positive tumors (> 10%) and HER2 3+ or neu amplified Cohort A Trastuzumab+Pertuzumab+Palbociclib+Fulvestrant (HPPF)

Cohort B Trastuzumab+Pertuzumab+Palbociclib (HPP) Allocation to Cohort B will be started after recruitment to Cohort A has been completed

Patients with ER positive tumors (> 10%), PgR positive, HER2 1+/2+ (without amplification) and Ki67 > 20% Cohort C Trastuzumab+Pertuzumab+Palbociclib+Fulvestrant (HPPF)

Trastuzumab 8 mg/kg loading dose IV, then 6 mg/kg IV q.3 wks (repeat for a total of 6 administrations) Pertuzumab 840 mg loading dose IV, then 420 mg IV q. 3 wks (repeat for a total of 6 administrations) Palbociclib 125 mg po q.d. x 21 q. 4 wks (= 1 cycle; repeat for a total of 5 cycles) Fulvestrant will be given intra-muscle at the dose of 500 mg every 4 weeks (repeat for 5 times) with an additional 500 mg dose given two weeks after the initial dose (total administrations including the additional one = 6)

The total duration of neoadjuvant palbociclib (5 cycles every 4 weeks) and fulvestrant (5 administrations every 4 weeks plus the additional dose given two weeks after the initial dose) was selected to match as closely as possible the total duration of the six planned 3-weekly administrations of trastuzumab and pertuzumab

Definitive surgery will be performed not earlier than 14 days and not later than 28 days after the last dose of any of the drugs in the combination reported above

After completion of the neoadjuvant and surgical treatment patients will receive irradiation as locally acceptable.

Patients will also continue to receive systemic drug therapy including chemotherapy (plus standard anti-HER2 treatment until completion of full 1 year if HER2 3+ or neu amplified, i.e. cohorts A and B) and endocrine therapy according to local guidelines at the Investigator's discretion.

Primary objectives:

  • Characterize changes of Ki67 from baseline before therapy and at 2 weeks and at surgery (approximately 22 weeks after start of neoadjuvant therapy with HPPF).
  • Characterize changes in apoptosis from baseline before therapy and at surgery (approximately 22 weeks after start of neoadjuvant therapy with HPPF).
  • Study the tolerability profile of the combination

Secondary objectives:

  • Assess the rate of pathological complete response (pCR) defined as ypT0-ypTis ypN0 at surgery
  • Define the clinical objective response rate at the end of the combination
  • Conduct molecular and clinical analyses to assess the presence of informative markers of benefit in addition to Ki67 and apoptosis
Keywords
HER2-positive, ER-positive, invasive, CDK4,6, Palbociclib, neoadjuvant treatment
Medical subject headings
Breast Neoplasms

What participants receive

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

  • TrastuzumabDrug

    Also called Herceptin

    Trastuzumab (8 mg/kg loading dose IV, then 6 mg/kg IV) will be given on day 1 q. 3 weeks for a total of 6 administrations

  • PertuzumabDrug

    Also called Perjeta

    Pertuzumab (840 mg as an i.v. infusion) will be given on day 1 q. 3 weeks for a total of 6 administration

  • PalbociclibDrug

    Also called Ibrabce

    Palbociclib will be given at the dose of 125 mg po q.d. x 21 every 4 weeks (i.e. 1 week rest period for a total of 5 cycles

  • FulvestrantDrug

    Also called Faslodex

    Fulvestrant will be administered according to local prescription guidelines and will be given intra-muscle at the dose of 500 mg every 4 weeks (repeat for 5 times) with an additional 500 mg dose given two weeks after the initial dose

Study groups in NCT02530424
Study groupRoleWhat they receive
Trast-pert-palbo-fulveExperimentalPatients will receive an association of drugs (trastuzumab, pertuzumab, palbociclib plus or minus fulvestrant) as neoadjuvant chemotherapy. Definitive surgery will be performed not earlier than 14 days and not later than 28 days after the last dose of any of the drugs in the combination. After completion of surgical treatment patients will receive irradiation as locally acceptable.
Receives: Drug: Trastuzumab; Drug: Pertuzumab; Drug: Palbociclib; Drug: Fulvestrant

What is being measured

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

  1. Serial measures of Ki67

    Changes in Ki67 scores from baseline before therapy, 2 weeks after and then at surgery

    Measured: Participants will be followed for the duration of protocol therapy, an expected average of 26 weeks

  2. Serial measures of apoptosis

    Changes in apoptosis biomarker scores from baseline before therapy and at surgery

    Measured: Participants will be followed for the duration of protocol therapy, an expected average of 26 weeks

Secondary outcomes (3)

  1. pathological complete response (pCR)

    Assess the rate of pathological complete response (pCR) defined as ypT0-ypTis ypN0 at surgery

    Measured: at surgery

  2. clinical objective response

    Assess the clinical objective response rate after medical therapy

    Measured: Participants will be followed for the duration of medical therapy, an expected average of 24 weeks

  3. Number of participants with adverse events as a Measure of Safety and Tolerability

    Number of participants with Adverse Events and related grade

    Measured: Participants will be followed for up to 7 months

Timeline

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

  1. First posted21 Aug 2015 (estimated)
  2. Study startMay 2015
  3. Primary completionSep 2019
  4. Study completionNov 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
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
102 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02530424
Sponsor's protocol ID
FM-14-B01
Acronym
NA-PHER2
Status last verified
Jul 2019
First submitted
19 Sep 2014
Last updated
15 Jul 2020
Results posted
No
Data monitoring committee
Yes

Publications

  • Vigano L, Locatelli A, Ulisse A, Galbardi B, Dugo M, Tosi D, Tacchetti C, Daniele T, Gyorffy B, Sica L, Macchini M, Zambetti M, Zambelli S, Bianchini G, Gianni L. Modulation of the Estrogen/erbB2 Receptors Cross-talk by CDK4/6 Inhibition Triggers Sustained Senescence in Estrogen Receptor- and ErbB2-positive Breast Cancer. Clin Cancer Res. 2022 May 13;28(10):2167-2179. doi: 10.1158/1078-0432.CCR-21-3185.

    PubMed 35254385

  • Gianni L, Colleoni M, Bisagni G, Mansutti M, Zamagni C, Del Mastro L, Zambelli S, Bianchini G, Frassoldati A, Maffeis I, Valagussa P, Viale G. Effects of neoadjuvant trastuzumab, pertuzumab and palbociclib on Ki67 in HER2 and ER-positive breast cancer. NPJ Breast Cancer. 2022 Jan 10;8(1):1. doi: 10.1038/s41523-021-00377-8.

    PubMed 35013314

  • Gianni L, Bisagni G, Colleoni M, Del Mastro L, Zamagni C, Mansutti M, Zambetti M, Frassoldati A, De Fato R, Valagussa P, Viale G. Neoadjuvant treatment with trastuzumab and pertuzumab plus palbociclib and fulvestrant in HER2-positive, ER-positive breast cancer (NA-PHER2): an exploratory, open-label, phase 2 study. Lancet Oncol. 2018 Feb;19(2):249-256. doi: 10.1016/S1470-2045(18)30001-9. Epub 2018 Jan 8.

    PubMed 29326029

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Trastuzumab, Pertuzumab and Palbociclib in people with Breast Neoplasms, run by Fondazione Michelangelo at 7 sites in Italy.

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 11 inclusion and 17 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 15 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Italy. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Serial measures of Ki67 (time frame: Participants will be followed for the duration of protocol therapy, an expected average of 26 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 NCT02530424, which also lists 3 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 15 Jul 2020.

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