Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Immune System Diseases

Symptoms and General Pathology

Breast Neoplasms

Hypersensitivity

Disease Progression

Breast Diseases

Skin Diseases

Bone Density Conservation Agents

Antineoplastic Agents

All Drugs and Chemicals

Tamoxifen

Fulvestrant

Exemestane

Letrozole

Palbociclib

Anastrozole

Protein Kinase Inhibitors

Enzyme Inhibitors

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)

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.

Endocrine therapy (non IMP)

Javier Cortes, MD PhD

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

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.

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

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

Measure histoscore (Hscore) levels of Ki67 and active caspase 3

Differences in expression profiles, assessed by RNA microarrays.

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.

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.

Patients with molecular patterns of resistance (Rb loss, biomarkers significant inhibition), mutations and expression profiles will be compared against patients without.

measure histoscore (Hscore) levels of the above targets

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Molecular Mechanisms of Resistance and Sensitivity to Palbociclib Re-challenge in ER+ mBC	NCT03184090	Metastatic Brea...	Palbociclib Endocrine thera...	18 Years -	MedSIR
Molecular Mechanisms of Resistance and Sensitivity to Palbociclib Re-challenge in ER+ mBC	NCT03184090	Metastatic Brea...	Palbociclib Endocrine thera...	18 Years -	MedSIR

Spots Global Cancer Trial Database for endocrine therapy (non imp)