Phase III Palbociclib With Endocrine Therapy vs. Capecitabine in HR+/HER2- MBC With Resistance to Aromatase Inhibitors (PEARL)
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|ClinicalTrials.gov Identifier: NCT02028507|
Recruitment Status : Active, not recruiting
First Posted : January 7, 2014
Last Update Posted : December 16, 2019
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Breast Cancer||Drug: Palbociclib Drug: Capecitabine Drug: Exemestane Drug: Fulvestrant||Phase 3|
296 patients have been randomized 1:1 between the experimental arm (Arm A: approximately 125 patients treated with palbociclib plus exemestane) and the control arm (Arm B: approximately 125 patients treated with capecitabine) before the approval of this protocol version (Cohort 1).
Approximately 300 patients will be randomized 1:1 between the experimental arm (Arm A: approximately 150 patients treated with palbociclib plus fulvestrant) and the control arm (Arm B: approximately 150 patients treated with capecitabine) from the approval of this protocol version (Cohort 2).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||596 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase III Study of Palbociclib in Combination With Exemestane or Fulvestrant vs. Chemotherapy (Capecitabine) in Hormonal Receptor Positive/HER2 Negative Metastatic Breast Cancer Patients With Resistance to Aromatase Inhibitors|
|Actual Study Start Date :||March 13, 2014|
|Actual Primary Completion Date :||January 14, 2019|
|Estimated Study Completion Date :||July 2020|
Experimental: Palbociclib plus Exemestane or Fulvestrant
Palbociclib 125 mg orally once daily on Day 1 to Day 21 followed by 7 days off treatment on every 28 days cycles in combination with
Other Name: Ibrance
Other Name: aromasil
Other Name: faslodex
Active Comparator: Capecitabine
Capecitabine, 1,250 mg/m2 twice daily for 2 weeks followed by a 1 week rest period, given as 3 weeks cycles. Capecitabine must be administered at a dose of 1,000 mg/m2 twice daily for 2 weeks followed by a 1 week of rest period, given as 3 weeks cycles, in patients over 70 years of age.
Other Name: Xeloda
- Progression-Free Survival (PFS) [ Time Frame: Approximately September 2019 ]The primary efficacy variable is PFS based on the investigator's assessment. PFS is defined as the time from randomization to the first documented progressive disease based on the investigator's assessment, using RECIST version 1.1, or death from any cause, whichever occurs first. Estrogen Receptor 1 (ESR1) mutational status will be determined in circulating free DNA (cDNA) obtained from baseline plasma samples and will be prospectively determined before the interims or final analyses. ESR1 mutational status will be blinded to the patients, investigators and study team.
- Objective Response (OR) [ Time Frame: Approximately September 2019 ]
Complete Response (CR) plus Partial Response (PR) based on the investigator's assessment according to the RECIST version 1.1 in patients randomized with measurable disease.
Tumor assessment will be performed at baseline, the same method of measurement used at baseline will be used for further evaluations, that will be conducted every 8 weeks (±7days). The best response across treatment will be recorded. OR is defined as the complete plus partial responses out of the patients who had measurable disease at baseline.
- Clinical Benefit (CB) [ Time Frame: Approximately September 2019 ]CB is defined as complete response (CR), partial response (PR), or stable disease (SD) based on the investigator´s assessment lasting more than 24 weeks according to the RECIST version 1.1 in all randomized patients (ITT population)
- Response Duration (RD) (RD) [ Time Frame: Approximately September 2019 ]RD is defined as the time from the first documentation of objective tumor response (CR or PR) to the first documented progressive disease using RECIST version 1.1 and based on the investigator's assessment, or to death due to any cause, whichever occurs first.
- Overall Survival (OS) [ Time Frame: Approximately July 2020 ]OS is defined as the time from the date of randomization to the date of death from any cause.
- The Number of Participants Who Experienced Adverse Events (AE) [ Time Frame: Day 1 of each cycle. ]Safety will be assessed by standard clinical and laboratory tests (hematology, serum chemistry). Adverse events grade will be defined by the NCI CTCAE v4.0.
- Exploratory Outcomes: biomarkers related to breast tumor sensitivity and/or resistance to palbociclib (e.g., Ki67, p16/CDKN2A, pRb, CyclinD and others) or breast cancer (e.g. PTEN, ERBB2, BRCA 1 and BRCA2). [ Time Frame: Approximately September 2019 ]Baseline biomarker values from most recently obtained tumor tissue (deeply recommended from metastatic tumor) will be used for central assessment of biomarkers related to breast tumor sensitivity and/or resistance to palbociclib (e.g., Ki67, p16/CDKN2A, pRb, CyclinD and others) or breast cancer (e.g. PTEN, ERBB2, BRCA1 and BRCA2). A whole blood sample will be collected for potential pharmacogenomic analyses related to drug response or adverse drug reactions. For example, putative safety biomarkers, drug metabolizing enzyme genes, drug transport protein genes, or genes thought to be related to the drug mechanism of action may be examined. Correlative plasma samples will be collected for exploratory analysis to analyze the pharmacodynamic (PD) treatment effects on circulating free DNA or RNA and explore specific breast cancer and efficacy predictive biomarkers (e.g. PIK3CA mutation). Sample will be collected from all patients, unless prohibited by local regulations.
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): NCT02028507
|Study Director:||Study Director||IiSGM, Universidad Complutense de Madrid, Madrid, Spain.|