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Metastatic Breast CancerPhase 2NCT04318223

Palbociclib Plus Fulvestrant in Women With Hormone Receptor Positive and Human Epidermal Growth Factor Receptor Type 2 Negative Locally Advanced or Metastatic Breast Cancer Previously Treated With a CDK4/6 Inhibitor in Combination With Hormonal Therapy

A Phase 2 study testing Palbociclib in people with Metastatic Breast Cancer and Locally Advanced Breast Cancer, run by Consorzio Oncotech at 19 sites in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The aim of the present study is to evaluate the efficacy and safety of palbociclib plus fulvestrant after failure of a combined treatment of hormonal therapy (aromatase inhibitor or tamoxifen ± LHRHa) plus a CDK4/6 inhibitor, in women with HR+ and HER2- LABC or MBC. Primary endpoint: 1. Read more about this study

Who is it for?
Ages 18 to 64 years, women only
What is being tested?
Palbociclib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
168 participants
Where
19 sitesItaly
Study dates
16 Jul 2019to 31 Jul 2023
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 to 64 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • Adult (≥ 18 years of age) pre or post-menopausal women with LABC or MBC not amenable to curative treatment by surgery or radiotherapy, progressing to a CDK4/6 inhibitor in combination with aromatase inhibitor or tamoxifen in the adjuvant or metastatic setting. To be enrolled in the present trial patients must have relapsed at least after 12 months from the last CDK4/6 dosage in the adjuvant setting or at progression from a first line combined hormonal treatment for metastatic disease with a CDK4/6 inhibitor plus AI or Tam with duration of, at least, 6 months. For metastatic disease, patients must have achieved, at least a stable disease while the first line hormonal treatment with a CDK4/6 inhibitor plus AI or Tam to be enrolled in the trial.
  • Patients receiving up to one line of chemotherapy before the first line hormonal treatment with a CDK4/6 inhibitor for metastatic disease may be enrolled in the study.
  • Histological confirmation of ER and/or PgR ≥ 1% and HER2 negative breast cancer (IHC status 0, 1+, 2+ and FISH not amplified).
  • Premenopausal women: in order to be eligible must have achieved surgical menopause with bilateral oophorectomy or ovarian radiation or medical menopause by treatment with a luteinizing hormone-releasing hormone (LHRH) agonist (LHRHa) for induction of ovarian suppression.
  • Radiological or objective evidence of recurrence or progression on or after the last systemic therapy prior to enrollment.
  • Patients who received ≤ 28 days of fulvestrant for second line advanced breast cancer treatment prior to study enrollment are eligible.
Show all 22Show fewer
  • Patients must have:
  • At least one lesion that can be accurately measured in at least one dimension ≥ 20 mm with conventional imaging techniques or ≥ 10 mm with spiral CT or MRI
  • Bone lesions: lytic or mixed (lytic + sclerotic) in the absence of measurable disease as defined above.
  • Adequate bone marrow and coagulation and adequate organ function defined as follows:
  • ANC > 1,000/mm3 (1.0 x 109/L);
  • Platelets > 75,000/mm3 (75 x 109/L);
  • Hemoglobin≥ 9 g/dL (90 g/L);
  • Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 60 ml/min as calculated using the method standard for the institution;
  • Total serum bilirubin≤1.5 x ULN (<2.5 ULN if Gilbert's disease);
  • AST and/or ALT≤ 3 x ULN (≤ 5 x ULN if liver metastases present);
  • Alkaline phosphatase ≤2.5 x ULN (≤ 5 x ULN if bone or liver metastases present);
  • ECOG Performance Status≤ 2;
  • Resolution of all acute toxic effects of prior therapy or surgical procedures to National Cancer Institute (NCI) CTCAE Grade ≤1 (except alopecia).
  • Estimated life expectancy of >12 weeks.
  • Patients must perform liquid biopsy at study entry and at disease progression. Tissue biopsy of the most accessible metastatic site at study entry and at disease progression are required but not mandatory.
  • Written informed consent obtained before any screening procedure and according to local guidelines.

Who cannot join

  • HER2-overexpressing patients by local laboratory testing (IHC3+ staining or in situ hybridization positive).
  • Patients who received > 1 line of chemotherapy as treatment for MBC.
  • Patients who received > 1 line of a CDK4/6 inhibitor in combination with hormonal treatment for LABC or MBC or who have relapsed at less than 12 months from the end of adjuvant treatment with a CDK4/6 inhibitor. For metastatic disease, patients with a progressive disease within the first 6 months of treatment while on first line therapy with a CDK4/6 inhibitor, will be excluded.
  • Patients receiving chemotherapy or any type of hormonal therapy after treatment with a CDK4/6 inhibitor for metastatic disease.
  • Patients interrupting the previous treatment with CDK4/6 inhibitor for cardiac and/or hepatic toxicity and not for disease progression.
  • Pregnant, lactating women.
Show all 25Show fewer
  • Known hypersensitivity to CDK4/6 inhibitors, fulvestrant, or to any of the excipients.
  • Radiotherapy within four weeks prior to enrollment (baseline/treatment start) except in case of localized radiotherapy for analgesic purpose or for lytic lesions at risk of fracture which can then be completed within two weeks prior to enrollment (baseline/treatment start). Patients must have recovered from radiotherapy toxicities prior to enrollment.
  • Currently receiving hormone replacement therapy, unless discontinued prior to enrollment.
  • Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use, at the time of study entry except in cases outlined below:
  • short duration (<2 weeks) of systemic corticosteroids is allowed (e.g., chronic obstructive pulmonary disease, anti-emetic);
  • low doses of corticosteroids for brain metastasis treatment is allowed.
  • Patients with symptomatic visceral disease in need of urgent disease control (e.g., significant dyspnea related to pulmonary lymphangitic carcinomatosis and lung metastases or clinically meaningful symptomatic liver metastasis at the judgement of treating investigator).
  • Symptomatic brain metastases.
  • Patients with a known history of HIV seropositivity.
  • Active, bleeding diathesis, or on oral anti-vitamin K medication (except low dose warfarin, low-molecular-weight heparin (LMWH) and acetylsalicylic acid or equivalent, as long as the INR is ≤ 2.0).
  • Any severe and/or uncontrolled medical conditions such as: unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤6 months prior to enrollment, serious uncontrolled cardiac arrhythmia.
  • Acute and chronic, active infectious disorders.
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of the study treatments (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome).
  • Inability to swallow oral medications.
  • Significant symptomatic deterioration of lung function.
  • Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A (Rifabutin, Rifampicin, Clarithromycin, Ketoconazole, Itroconazole, Voriconazole, Ritinavir, Telithromycin) within the last 5 days prior to enrollment.
  • History of non-compliance to medical regimens.
  • Patients refusing to perform liquid biopsy at study entry and disease progression.
  • Patients unwilling to or unable to comply with the protocol.

Trial locations and contacts

19 sites in 1 country.

Grazia Arpino, MD contact

+390817463772

grazia.arpino@unina.it

19 sites in 1 country

Italy19 sites, 19 recruiting

  • Centro di Riferimento oncologico

    Aviano, Pordenone, 33081

    Fabio Puglisi, MD, fabio.puglisi@uniud.it

    Fabio Puglisi, MD

    Not yet recruiting

  • Ospedale Sacro Cuore di Gesù Fatebenefratelli

    Benevento, 82100

    Antonio Febbraro, MD, +390824771271, antoniofebbraro@virgilio.it

    Antonio Febbraro, MD

    Not yet recruiting

  • A.O. Osp. Riuniti - ASST PAPA GIOVANNI 23

    Bergamo, 24127

    Paola Lucia Poletti, MD, +390352673694, ppoletti@asst-pg23.it

    Paola Lucia Poletti, MD

    Not yet recruiting

  • Ospedale di Brindisi "Perrino"

    Brindisi, 72100

    Saverio Cinieri, MD, +390831537218, saverio.cinieri@asl.brindisi.it

    Saverio Cinieri, MD

    Not yet recruiting

  • Fondazione del Piemonte per l'Oncologia

    Candiolo, Torino, 10060

    Filippo Montemurro, MD, +390119933253, filippo.montemurro@ircc.it

    Filippo Montemurro, MD

    Not yet recruiting

  • Ospedale Civile S. Giovanni di Dio

    Frattamaggiore, Napoli, 80027

    Salvatore Del Prete, MD, +39081889133, salvatore.delprete@aslnapoli2nord.it

    Salvatore Del Prete, MD

    Not yet recruiting

  • Ospedale Policnico San Martino

    Genova, 16132

    Lucia Del Mastro, MD, +390105558904, lucia.delmastro@hsanmartino.it

    Lucia Del Mastro, MD

    Not yet recruiting

  • Ospedale Vito Fazzi

    Lecce, 73100

    Giuseppe Cairo, MD

    Giuseppe Cairo, MD

    Not yet recruiting

  • Azienda Ospedaliera Papardo

    Messina, 98158

    Vincenzo Adamo, MD, +390903996150, vadamo@unime.it

    Vincenzo Adamo, MD

    Recruiting

  • Azienda Ospedaliero - Universitaria di Modena

    Modena, 41125

    Angela Toss, MD, +390594223286, angela.toss@unimore.it

    Angela Toss, MD

    Not yet recruiting

  • A.O.U. Seconda Universita' degli Studi di Napoli

    Naples, 80131

    Michele Orditura, MD, 0815666713, michele.orditura@unicampania.it

    Michele Orditura, MD

    Recruiting

  • Azienda Ospedaliera 'A. CARDARELLI'

    Naples, 80131

    Ferdinando Riccardi, MD, +390817472174, nando.riccardi@alice.it

    Ferdinando Riccardi, MD

    Not yet recruiting

  • Azienda Ospedaliera dei Colli - P.Monaldi

    Naples, 80131

    Vincenzo Montesarchio, MD, +390817065286, dott.vincenzomontesarchio@gmail.com

    Vincenzo Montesarchio, MD

    Recruiting

  • Istituto Nazionale Tumori IRCCS Pascale

    Naples, 80131

    Michelino De Laurentiis, MD, +390815903699, delauren@breastunit.org

    Michelino De Laurentiis, MD

    Not yet recruiting

  • Università degli Studi di Napoli "Federico II"

    Naples, 80131

    Grazia Arpino, MD, +390817463772, grazia.arpino@unina.it

    Grazia Arpino, MD

    Recruiting

  • A.O.U. Pisana

    Pisa

    Andrea Michelotti, MD, +39050993173, andre.michelotti@gmail.com

    Andrea Michelotti, MD

    Not yet recruiting

  • Nuovo ospedale di Prato - S. Stefano

    Prato, Firenze, 59100

    Giuseppina Sanna, MD, +390574802531, giuseppina.sanna@uslcentro.toscana.it

    Giuseppina Sanna, MD

    Not yet recruiting

  • Istituto Nazionale Tumori Regina Elena (IRE

    Roma, 00144

    Alessandra Fabi, MD, +390652665144, alessandra.fabi@virgilio.it

    Alessandra Fabi, MD

    Recruiting

  • Ospedale Sandro Pertini

    Roma, 00157

    Teresa Gamucci, MD, +390641433385, teresa.gamucci@aslroma2.it

    Teresa Gamucci, MD

    Recruiting

Other trials in Italy

About this study

Official title: Palbociclib Plus Fulvestrant in Women With Hormone Receptor Positive and Human Epidermal Growth Factor Receptor Type 2 Negative Locally Advanced or Metastatic Breast Cancer Previously Treated With a CDK4/6 Inhibitor in Combination With Hormonal Therapy: a Multicenter, Phase II Trial

The aim of the present study is to evaluate the efficacy and safety of palbociclib plus fulvestrant after failure of a combined treatment of hormonal therapy (aromatase inhibitor or tamoxifen ± LHRHa) plus a CDK4/6 inhibitor, in women with HR+ and HER2- LABC or MBC.

Primary endpoint:

Read more
  1. To assess the clinical benefit rate (CBR) of the combination treatment palbociclib plus fulvestrant at progression of a combined treatment of hormonal therapy (aromatase inhibitor or tamoxifen ± LHRHa) and a CDK4/6 inhibitor. Clinical benefit rate for primary efficacy endpoints derivation will be based on the local (treating center's) radiologist's/investigator's tumor assessment.
  • For patients with measurable disease at baseline, progression will be determined according to the RECIST criteria v1.1.
  • In the absence of measurable disease at baseline, patients with bone only lesions, lytic or mixed (lytic + sclerotic), will be allowed to enter the study and the following will be considered disease progression among these patients:
  • The appearance of one or more new lytic lesions in bone,
  • The appearance of one or more new lesions outside of bone,
  • Unequivocal progression of existing bone lesions. Note: Pathologic fracture, new compression fracture, or complications of bone metastases will not be considered as evidence of disease progression, unless one of the above-mentioned criteria is fulfilled.
  1. To assess the Quality of Life (QoL) of patients receiving the combination treatment palbociclib plus fulvestrant at progression of a combined treatment of hormonal therapy (aromatase inhibitor or tamoxifen ± LHRHa) and a CDK4/6 inhibitor.

Secondary Endpoints:

  1. To evaluate the efficacy of the combination of fulvestrant plus palbociclib at the progression of a combined treatment of hormonal therapy (aromatase inhibitor or tamoxifen ± LHRHa) and CDK4/6 inhibitors with respect to:
  • Overall response rate (ORR)
  • Progression Free Survival (PFS)
  • Overall Survival (OS)
  • Safety and tolerability
  1. To assess predictive biomarkers of response/resistance to fulvestrant plus palbociclib using metastatic tumor tissue samples and liquid biopsies.

This study will be performed in pre- and post-menopausal women with HR+/HER2- LABC or MBC whose disease is progressing to a CDK4/6 inhibitor in combination with hormonal therapy (aromatase inhibitor or tamoxifen ± LHRHa).

Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first.

Read the detailed description

This is a Phase II, multicentre, single-arm study following a Simon's two-stage optimal design

Screening phase At screening, the investigator or his/her authorized designee will assign a unique number to patients being considered for the study. The patient should provide a signed Informed Consent Form prior to any study screening evaluations. Once the patient Informed Consent Form has been signed and eligibility is confirmed (all inclusion/exclusion criteria has been verified), the patient can be enrolled. All screening evaluations will be performed within 28 days prior to Treatment Day 1. Patients may be re-screened.

Treatment phase Eligible patients will receive Fulvestrant plus palbociclib. Patients will be treated with fulvestrant 500 mg i.m. on Days 1, 15 and 29 and every 28 days thereafter and palbociclib125 mg oral day 1 to 21 every 28 days.

Dose adjustment (reduction, interruption) according to toxicity of study treatment will be allowed. Study treatment will continue until one of the following conditions apply - whichever comes first:

  • tumor progression
  • unacceptable toxicity according to investigator's judgment
  • death
  • discontinuation from the study for any other reason Further treatments after discontinuation will be at the investigator's discretion. During the study, visits will be performed monthly and at the end of treatment. Tumor assessment will be performed every 3 cycle of treatment.

For each patient enrolled in the present study a blood sample (mandatory) at study enrollment and at disease progression (mandatory) will be provided. Additionally, a tissue sample from the most accessible metastatic site will be collected at study enrollment and at disease progression (optional). Blood and tumor samples will be used to investigate the mechanisms of response and resistance to therapy with palbociclib in combination with fulvestrant.

Being tested
Palbociclib
Keywords
hormone receptor positive, human epidermal growth factor receptor type 2 negative
Medical subject headings
Breast Neoplasms

What participants receive

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

  • PalbociclibDrug

    Patients will be enrolled into the study and assign to receive Palbociclib 125 mg/day orally for 3 weeks followed by 1 week off plus fulvestrant 500 mg intramuscularly on Days 1 and 15 of Cycle 1, every 28 days (+/- 7 days) thereafter starting from Day 1 of Cycle 1

Study groups in NCT04318223
Study groupRoleWhat they receive
single-arm study following a Simon's two-stage optimal designExperimentalSingle-arm study with the primary objective of assessing the efficacy and safety of palbociclib in combination with fulvestrant (Faslodex) in women with HR+, HER2-negative metastatic breast cancer, regardless of their menopausal status, whose disease has progressed after prior treatment with AI plus a CDK4/6 inhibitor.
Receives: Drug: Palbociclib

What is being measured

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

  1. Clinical Benefit Response (CBR)

    To assess the clinical benefit rate (CBR) of the treatment, the Clinical Benefit Response (CBR) is defined as complete response (CR) or partial response (PR) or stable disease (SD) >24 weeks according to the RECIST version 1.1 recorded in the time period between enrollment and disease progression or death of any cause. CBR with the corresponding 95% Confidence Interval (95% C.I.) will be estimated using the exact binomial method. A Simon optimal two-stage design will be used to exclude a clinical benefit rate (CBR) of 30% (p0 = 0.30) with a clinical relevant target of 40% (p1 = 0.40) using a one-sided alpha-level of 0.05 and a power of 0.80. Fifty-nine (59) subjects will be enrolled in the first phase. If nineteen (19) of fewer CR+PR+SD will be observed, the study will be terminated. Otherwise the treatment will be considered worthy of further investigation and 109 more subjects will be enrolled for a total sample size of 168 subjects.

    Measured: About 48 months

  2. Patient Reported Outcomes (PRO)

    Breast cancer-specific quality of life total scale scores and single item scale scores will be summarized by descriptive summary tables at baseline and over time. The mean changes from baseline will also be summarized using descriptive statistics. Longitudinal trajectories of total scale scores will be modelled using linear mixed models with random intercept to account for subject specific baseline assessment; time will be modeled continuously using days since baseline; potential non linear trend will be examined by adding quadratic terms to the model. Selection of the best model will be based on Akaike Information Criterion (AIC).

    Measured: About 48 months

Secondary outcomes (4)

  1. Efficacy of the combination of fulvestrant plus palbociclib

    To evaluate the efficacy of the combination of fulvestrant plus palbociclib at the progression of a combined treatment of hormonal therapy and CDK4/6 inhibitors with respect to:

    • Overall response rate (ORR) :will be estimated by dividing the number of patients with OR (CR or PR) by the number of patients ("response rate"). A 95% CI for the response rates will be provided using the exact binomial method

    Measured: About 48 months

  2. Efficacy of the combination of fulvestrant plus palbociclib

    To evaluate the efficacy of the combination of fulvestrant plus palbociclib at the progression of a combined treatment of hormonal therapy and CDK4/6 inhibitors with respect to:

    • Overall Survival (OS) :the median event times and 95% CIs will be estimated. The 1-year survival probability will be estimated using the Kaplan-Meier method and a two sided 95% CI for the log [-log(1-year survival probability)] will be calculated using a normal approximation using the Greenwood's formula

    Measured: About 48 months

  3. Efficacy of the combination of fulvestrant plus palbociclib

    To evaluate the efficacy of the combination of fulvestrant plus palbociclib at the progression of a combined treatment of hormonal therapy and CDK4/6 inhibitors with respect to:

    • Progression Free Survival (PFS) :the analyses of PFS will be performed in the ITT population. PFS time will be summarized using the Kaplan-Meier method and displayed graphically where appropriate. 95% CIs for the 25th, 50th and 75th percentiles of the event-free time (if reached) will be reported.

    Measured: About 48 months

  4. Predictive biomarkers of response/resistance

    To assess predictive biomarkers of response/resistance to fulvestrant plus palbociclib using metastatic tumor tissue samples and liquid biopsies. Patients must perform liquid biopsy at study entry and at disease progression.

    Biopsies will be used to investigate expression levels and/or genetic alteration of cell cycle components as well as additional molecular pathways potentially responsible for resistance to CDK4/6 inhibitors.

    Measured: About 48 months

Timeline

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

  1. First posted23 Mar 2020
  2. Study start16 Jul 2019
  3. Primary completion31 Jul 2023 (estimated)
  4. Study completion31 Jul 2023 (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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
This is a Phase II, multicentre, single-arm study following a Simon's two-stage optimal design
Masking
None (open label)
Enrolment
168 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04318223
Sponsor's protocol ID
GIM24-PALBO-BP
Status last verified
Mar 2020
First submitted
2 Dec 2019
Last updated
23 Mar 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Palbociclib in people with Metastatic Breast Cancer and Locally Advanced Breast Cancer, run by Consorzio Oncotech at 19 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 22 inclusion and 25 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: status not confirmed, as of the sponsor's last update on 23 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 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?

Results are not available in the source record.

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

Contact Grazia Arpino, MD (+390817463772, grazia.arpino@unina.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinical Benefit Response (CBR) (time frame: About 48 months). 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 NCT04318223.

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 23 Mar 2020.

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