Molecular Mechanisms of Resistance and Sensitivity to Palbociclib Re-challenge in ER+ mBC (BioPER)
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|ClinicalTrials.gov Identifier: NCT03184090|
Recruitment Status : Active, not recruiting
First Posted : June 12, 2017
Last Update Posted : August 26, 2019
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
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Breast Cancer||Drug: Palbociclib Drug: Endocrine therapy (non IMP)||Phase 2|
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 :||Interventional (Clinical Trial)|
|Actual Enrollment :||33 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Multicentre, 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 (BioPER)|
|Actual Study Start Date :||June 28, 2017|
|Estimated Primary Completion Date :||November 2019|
|Estimated Study Completion Date :||November 2019|
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.
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.
- 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.
- 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.
- 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.
- 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
- 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
- Measure differences in expression profile, assessed by RNA microarrays [ Time Frame: Baseline-Up to 24 months ]Differences in expression profiles, assessed by RNA microarrays.
- Correlation between inhibitory effects of palbociclib and clinical response [ Time Frame: 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 ]
- 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03184090
|Istituto Europeo di Oncologia|
|Azienda Sanitaria Universitaria Integrata di Udine|
|Badalona, Barcelona, Spain|
|L'Hospitalet de Llobregat, Barcelona, Spain, 08007|
|Clinico Universitario A Coruña|
|A Coruña, Spain|
|Hospital del Mar|
|Barcelona, Spain, 08003|
|Hospital Universitari Vall d'Hebron|
|Hospital Provincial de Castellón|
|Castellón De La Plana, Spain|
|Hospital Reina Sofia|
|Hospital La Paz|
|Hospital Sant Joan de Reus|
|Hospital Virgen del Rocío|
|Hospital Clinico Universitario de Valencia|
|Hospital Universitari i Politecnic La Fe|
|Instituto Valenciano de Oncología - IVO|
|Principal Investigator:||Javier Cortes, MD PhD||Hospital Universitario Ramon y Cajal|