Molecular Mechanisms of Resistance and Sensitivity to Palbociclib Re-challenge in ER+ mBC (BioPER)

June 14, 2022 updated by: MedSIR

An International, Non-controlled Phase II Trial to Identify the Molecular Mechanisms of Resistance and Sensitivity to Palbociclib Re-challenge Upon Progression to a Palbociclib Combination in ER-positive Metastatic Breast Cancer Patients

This is an international, open-label, non-controlled, multicenter phase II clinical trial with two different primary objectives: a biological and a clinical objective.

From a clinical point of view, the objective is to assess the clinical benefit of the combination of palbociclib and hormonotherapy in patients with advance breast cancer that had previously received endocrine therapy in combination with palbociclib and had achieved clinical benefit during palbociclib treatment with subsequent disease progression.

From a biological point of view, the challenge is to define a molecular profile that allow identifying patients that could benefit more from continuing on palbociclib after progression on a prior palbociclib-containing regimen

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Eligible patients will receive palbociclib capsules orally for 21 days every four weeks in combination with endocrine therapy (physician's choice based on prior administered agent including tamoxifen, exemestane, fulvestrant, anastrozole, or letrozole).

Patients will receive treatment until disease progression (with the exception of patients who develop isolated progression in the brain), unacceptable toxicity, death, or discontinuation from the study treatment for any other reason.

Patients discontinuing the study treatment period will enter a post-treatment follow-up period during which survival and new anti-cancer therapy information will be collected every six months (± 14 days) from the last dose of investigational product. The treatment follow-up period will conclude at six months after the last patient has received first treatment dose in the study.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
33

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milan, Italy
        • Istituto Europeo Di Oncologia
      • Udine, Italy
        • Azienda Sanitaria Universitaria integrata di Udine
  • Spain
      • A Coruña, Spain
        • Clinico Universitario A Coruña
      • Barcelona, Spain
        • Hospital Universitari Vall d'Hebron
      • Barcelona, Spain, 08003
        • Hospital del Mar
      • Castellón De La Plana, Spain
        • Hospital Provincial de Castellon
      • Cordoba, Spain
        • Hospital Reina Sofia
      • Madrid, Spain
        • Hospital La Paz
      • Reus, Spain
        • Hospital Sant Joan de Reus
      • Sevilla, Spain
        • Hospital Virgen del Rocío
      • Valencia, Spain
        • Hospital Clinico Universitario de Valencia
      • Valencia, Spain
        • Hospital Universitari i Politecnic La Fe
      • Valencia, Spain
        • Instituto Valenciano de Oncologia - IVO
    • Barcelona
      • Badalona, Barcelona, Spain
        • Ico Badalona
      • L'Hospitalet de Llobregat, Barcelona, Spain, 08007
        • ICO L'Hospitalet

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Pre- and postmenopausal women age ≥ 18 years (Premenopausal women must be treated with LHRH analogues for at least 28 days prior to study entry)
  • Hormone receptor-positive [estrogen receptor (ER) and/or progesterone receptor (PR)] and HER2-negative
  • Locally advanced or mBC that had previously received no more than two prior lines of endocrine therapy and no more than one prior line of chemotherapy for advanced disease.
  • Inmmediate previous treatment with palbociclib in combination with endocrine therapy had achieved clinical benefit during palbociclib-based treatment
  • Evidence of measurable and biopsable metastatic disease is required
  • Confirmed disease progression on immediate previous palbociclib plus endocrine therapy.
  • Last dose of palbociclib administered no later than eight weeks and not earlier than three weeks from study entry.
  • No prior use of at least one of the reasonable endocrine therapy options: tamoxifen, fulvestrant, letrozole/anastrozole, or exemestane.
  • Patients agree to collection of blood samples (liquid biopsy) and collection of metastatic tumour sample (biopsy) at the time of inclusion and progression (if appropriate).
  • Adequate organ function.
  • Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures

Exclusion criteria

  • HR or HER2 unknown disease.
  • HER2-positive disease based on local laboratory results [performed by immunohistochemistry/fluorescence in situ hybridization (FISH)].
  • Locally advanced breast cancer candidate for a local treatment with a radical intention.
  • Formal contraindication to endocrine therapy.
  • Progressing central nervous system (CNS) disease.
  • Patients with exclusive non-measurable/evaluable disease.
  • Other malignancies within the past five years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix.
  • Major surgery (defined as requiring general anaesthesia) or significant traumatic injury within four weeks of start of study drug, or patients who have not recovered from the side effects of any major surgery, or patients that may require major surgery during the course of the study.
  • Patients with an active bleeding diathesis, previous history of bleeding diathesis, or anti-coagulation treatment (the use of low molecular weight heparin is allowed as soon as it is used as prophylaxis intention).
  • Have a serious concomitant systemic disorder (i.e., active infection including HIV, or cardiac disease) incompatible with the study (at the discretion of investigator).
  • Are unable to swallow tablets.
  • History of malabsorption syndrome or other condition that would interfere with enteral absorption.
  • Chronic daily treatment with corticosteroids with a dose of ≥10 mg/day methylprednisolone equivalent (excluding inhaled steroids).
  • QTc >480 msec on basal assessments, personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes (TdP).
  • Uncontrolled electrolyte disorders that can compound the effects of a QTc-prolonging drug (i.e., hypocalcemia, hypokalemia, or hypomagnesemia).
  • Known hypersensitivity to any palbociclib excipients.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Palbociclib + Endocrine Therapy

Patients will receive palbociclib capsules orally for 21 days every four weeks in combination with endocrine therapy (physician's choice based on prior administered agent including tamoxifen, exemestane, fulvestrant, anastrozole, or letrozole).

Treatment will continue until disease progression (with the exception of patients who develop isolated progression in the brain), unacceptable toxicity, death, or discontinuation from the study treatment for any other reason.
Drug: Palbociclib
palbociclib in combination with endocrine therapy (investigator's choice)
Drug: Endocrine therapy (non IMP)
Endocrine therapy (physician's choice based on prior administered agent including tamoxifen, exemestane, fulvestrant, anastrozole, or letrozole). Endocrine therapy must be different from previous treatment line.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
molecular patterns of resistance [with a special focus on retinoblastoma (Rb) status] upon progression to palbociclib plus endocrine therapy in patients who previously achieved clinical benefit with the combination
Time Frame: Baseline-Up to 24 months
the percentage of patients with Rb loss [as defined by loss of expression, copy number variation (CNV), somatic mutation, or methylation dependent silencing]. The evaluation criteria will be the characterization of the molecular patterns of resistance with greater than 20% prevalence.
Baseline-Up to 24 months
clinical activity of the combination of palbociclib and endocrine therapy after prior progression to palbociclib in endocrine-sensitive patients.
Time Frame: Baseline-Up to 24 months
percentage of patients that achieve clinical benefit (CBR) defined as complete response, partial response, or stable disease for at least 24 weeks per RECIST v.1.1.
Baseline-Up to 24 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Compare clinical activity with molecular patterns of resistance.
Time Frame: Baseline-Up to 24 months
Patients with molecular patterns of resistance (Rb loss, biomarkers significant inhibition), mutations and expression profiles will be compared against patients without.
Baseline-Up to 24 months
Measure changes of immunostaining of Rb targets (E2F, DNMT, HIF1alpha, and SKP2) as a result of CDK4 and CDK6 inhibition and the potential predictive value of cyclin D, cyclin E, p16, p18, p21, and p27, in CDK4, and CDK6 inhibition
Time Frame: Baseline-Up to 24 months
measure histoscore (Hscore) levels of the above targets
Baseline-Up to 24 months

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Measure senescence and apoptosis (Ki67 and active caspase 3) in subgroups of patients with varying clinical responses.
Time Frame: Baseline-Up to 24 months
Measure histoscore (Hscore) levels of Ki67 and active caspase 3
Baseline-Up to 24 months
Measure differences in expression profile, assessed by RNA microarrays
Time Frame: Baseline-Up to 24 months
Differences in expression profiles, assessed by RNA microarrays.
Baseline-Up to 24 months
Correlation between inhibitory effects of palbociclib and clinical response
Time Frame: Baseline-Up to 24 months
Baseline-Up to 24 months
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs grade 3 and 4 and Serious Adverse Events)
Time Frame: Baseline-Up to 24 months
Baseline-Up to 24 months
Compare inhibitory effects of palbociclib and clinical response in patients with visceral disease or patients who received prior (neo) adjuvant hormonal therapy
Time Frame: Baseline-Up to 24 months
Baseline-Up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
MedSIR

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Javier Cortes, MD PhD, Hospital Universitario Ramon y Cajal

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 28, 2017

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 27, 2020

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 27, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 6, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 8, 2017

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 12, 2017

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 21, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 14, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MedOPP089
  • 2015-003892-31 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Metastatic Breast Cancer

Clinical Trials on Palbociclib

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings