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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-003170-27 | EudraCT Number |
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| Name | Class |
|---|---|
| Pfizer | INDUSTRY |
| AstraZeneca | INDUSTRY |
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This is an international (4 countries) randomized phase III study with 2 cohorts, patients will be randomized 1:1 to endocrine therapy (cohort 1: exemestane 25 mg daily, cohort 2: fulvestrant 500mg days 1 and 15 cycle 1 and then day 1 every 4 weeks) plus palbociclib (125 mg daily x3 weeks every 4 weeks) vs. capecitabine (1,250 mg/m2 twice daily x2 weeks every 3 weeks). Postmenopausal patients with HR+/HER2 MBC are eligible if resistant to previous nonsteroidal aromatase inhibitors (NSAI) (letrozole or anastrozole) in cohort 1 or previous aromatase inhibitors (AI) (letrozole, anastrozole or exemestane) in cohort 2 defined as: recurrence while on or within 12 months after the end of adjuvant treatment with NSAI/AI or progression while on or within 1 month after the end of treatment with NSAI/AI for MBC. Previous chemotherapy is permitted either in the (neo)adjuvant setting and/or as first line for MBC. Patients must have measurable disease according to RECIST 1.1 or bone lesions, lytic or mixed, in the absence of measurable disease.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: Palbociclib plus Exemestane | Experimental | - Cohort 1: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 Exemestane 25 mg orally once daily. |
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| Cohort 1:Capecitabine | Active Comparator | Cohort 1: 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. |
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| Cohort 2: Palbociclib plus Fulvestrant | Experimental | - Cohort 2: 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 Fulvestrant 500 mg on Days 1 and 15 of Cycle 1, and Day 1 of each subsequent 28 days Cycle. |
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| Cohort 2:Capecitabine | Active Comparator | Cohort 2: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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Palbociclib | Drug |
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| Measure | Description | Time Frame |
|---|---|---|
| Progression-Free Survival (PFS) | 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. Disease assessments will be performed at baseline and every 8 weeks (± 7 days) from the start of treatment and every 12 weeks (±7 days) after 120 weeks of treatment 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. | Through study treatment, and average of 8 months |
| Measure | Description | Time Frame |
|---|---|---|
| PFS Estrogen Receptor 1 (ESR1) Wild Type | 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. PFS data will be censored on the date of the last tumor assessment on study for patients who do not have objective tumor progression and who do not die while on study. Patients lacking an evaluation of tumor response after randomization will have their PFS time censored on the date of randomization with 1 day duration. Additionally, patients who start a new anti-cancer therapy prior to documented PD will be censored at the date of the last tumor assessment prior to the start of the new therapy. |
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Inclusion Criteria:
The patient has signed the informed consent document.
a) Patients in cohort 1: Females with histologically confirmed MBC whose disease is resistant to previous non-steroidal aromatase inhibitors (letrozole or anastrozole) b) Patients in cohort 2: Females with histologically confirmed MBC whose disease was resistant to previous aromatase inhibitors (exemestane, letrozole or anastrozole).
Resistance is defined as: Recurrence while on or within 12 months after the end of adjuvant treatment with NSAI/AI or Progression while on or within 1 month after the end of treatment with NSAI/AI for advanced disease.
Previous chemotherapy is permitted either in the (neo) adjuvant setting and/or first line therapy for MBC (chemotherapy administered as "second adjuvant therapy" for locoregional recurrence should be considered as first line chemotherapy for MBC).
It is not mandatory to have exemestane, letrozole or anastrozole as the most recent treatment before randomization but recurrence or progression of breast cancer while receiving (or immediately after the enf of) the most recent systemic therapy has to be documented before randomization.
Hormonal receptor positive (HR+) breast cancer based on local laboratory determination. HR+ defined as major or equal to 1 percent positive cells by Immunohistochemistry (IHC) for ER and/or Progesterone Receptor (PgR).
Documented HER2 negative breast cancer based on local laboratory determination on most recent tumor biopsy. HER2 negative tumor is determined as IHC score 0 or 1+ or negative by ISH (FISH/Chromogenic In Situ Hybridization (CISH)/SISH) defined as a HER2/CEP17 ratio minor to 2 or for single probe assessment a HER2 copy number minor to 4.
Measurable disease or at least one bone lesion, lytic or mixed (lytic+blastic), which has not been previously irradiated and is assessable by CT/MRI in the absence of measurable disease according to RECIST 1.1 criteria.
Patient is at least 18 years of age.
Eastern Cooperative Oncology Group (ECOG) Performance Status minor or equal to 1.
Life expectancy major or equal to 12 weeks.
Adequate organ and bone marrow function.
Postmenopausal women defined as women with:
Prior bilateral surgical oophorectomy, or Age > 60 years, or Age < 60 years and medically confirmed post-menopausal status defined as spontaneous cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause or follicle-stimulating hormone (FSH) and estradiol blood levels in their respective postmenopausal ranges
Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI CTCAE version 4.0 Grade minor or equal to 1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator´s discretion).
Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
Exclusion Criteria:
Have received more than 1 prior chemotherapy regimen for MBC. (NOTE: Chemotherapy administered as "second adjuvant therapy" for locoregional recurrence should be considered one prior chemotherapy for MBC).Other previous anticancer endocrine treatments for advanced disease are allowed.
Patients with advanced, symptomatic, visceral spread that are at risk of life-threatening complications in the short term (including patients with massive uncontrolled effusions (pleural, pericardial, peritoneal), pulmonary lymphangitis and over 50% liver involvement).
Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases or cord compression are eligible if they have been definitively treated with local therapy (eg, radiotherapy,) and are clinically stable off anticonvulsants and steroids for at least 4 weeks before randomization.
Prior treatment with any CDK4/6, mTOR or PI3K inhibitor (any agent whose mechanism of action is to inhibit the PI3 kinase-mTOR pathway) or capecitabine.
a) Patients included in cohort 1: Prior treatment with exemestane in the metastatic setting. If the patient has received exemestane in the adjuvant setting and developed MBC, she will be eligible for the study provided:
Patients treated within the last 7 days prior to randomization with:
Patients who received before randomization:
Diagnosis of any other malignancy within 3 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.
QTc major 480msec, family or 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 (eg, hypocalcemia, hypokalemia, hypomagnesemia).
Any of the following within 6 months of randomization: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE version 4.0 Grade major or equal to 2, atrial fibrillation of any grade, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism.
Difficulties to swallow tablets, malabsorption syndrome disease significantly affecting gastrointestinal function, resection of the stomach or small bowel, or active inflammatory bowel disease or chronic diarrhea.
Known hypersensitivity to exemestane, palbociclib, capecitabine, fulvestrant or any of their excipients.
Any of the following contraindications for chemotherapy with capecitabine:
Only for patients in Cohort 2 any of the following contraindications for treatment with fulvestrant:
- Bleeding diathesis (i.e., disseminated intravascular coagulation, clotting factor deficiency) or long-term anticoagulant therapy (other than antiplatelet therapy and low dose warfarin) provided that the International Normalised Ratio (INR) is less than 1.6.
Known human immunodeficiency virus infection.
Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
Recent or active suicidal ideation or behavior
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | IiSGM, Universidad Complutense de Madrid, Madrid, Spain. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Universitätsklinik für Innere Medizin III | Salzburg | 5020 | Austria | |||
| Landes-Krankenhaus Steyr |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33385521 | Result | Martin M, Zielinski C, Ruiz-Borrego M, Carrasco E, Turner N, Ciruelos EM, Munoz M, Bermejo B, Margeli M, Anton A, Kahan Z, Csoszi T, Casas MI, Murillo L, Morales S, Alba E, Gal-Yam E, Guerrero-Zotano A, Calvo L, de la Haba-Rodriguez J, Ramos M, Alvarez I, Garcia-Palomo A, Huang Bartlett C, Koehler M, Caballero R, Corsaro M, Huang X, Garcia-Saenz JA, Chacon JI, Swift C, Thallinger C, Gil-Gil M. Palbociclib in combination with endocrine therapy versus capecitabine in hormonal receptor-positive, human epidermal growth factor 2-negative, aromatase inhibitor-resistant metastatic breast cancer: a phase III randomised controlled trial-PEARL. Ann Oncol. 2021 Apr;32(4):488-499. doi: 10.1016/j.annonc.2020.12.013. Epub 2020 Dec 29. | |
| 35429901 |
| Label | URL |
|---|---|
| GEICAM is a Spanish Breast Cancer Research Group | View source |
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92 patients were screening failure. A total of 601 patients were included in this study from March 2014 to July 2018. Cohort 1 included 296 patients (153 on palbociclib plus exemestane and 143 on capecitabine) and cohort 2 included 305 patients (149 on palbociclib plus fulvestrant and 156 on capecitabine).
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1: Palbociclib Plus Exemestane | Cohort 1: 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 Exemestane 25 mg orally once daily. Palbociclib Exemestane |
| FG001 | Cohort 1: Capecitabine |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 5, 2019 | Feb 16, 2021 |
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| Capecitabine | Drug |
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| Exemestane | Drug |
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| Fulvestrant | Drug |
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| From randomization date to date of first documentation of progression or death (an average of 8 months) |
| Overall Survival (OS) ESR1 Wild Type | OS is defined as the time from the date of randomization to the date of death from any cause. | From randomization until death (up to approximately 34 months) |
| Objective Response Rate (ORR) ESR1 Wild Type | 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. | Through study treatment, and average of 8 months |
| Clinical Benefit Rate (CBR) ESR1 Wild Type | 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). Per RECIST, CR is defined as the disappearance of all target lesions; PR is defined as an >=30% decrease in the sum of the longest diameter of target lesions; SD is defined as a failure to meet criteria for CR or PR in the absence of progressive disease. Overall Response (OR) = CR + PR. | Through study treatment, and average of 8 months |
| Response Duration (RD) ESR1 Wild Type | Tumor response was assessed using Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria. RD was defined as the time from the first documentation of objective tumor response (complete response (CR) or partial response (PR)) to the first documented progressive disease (PD), or to death due to any cause, whichever occurs first. Per RECIST, CR is defined as the disappearance of all target lesions; PR is defined as an >=30% decrease in the sum of the longest diameter of target lesions; PD is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions | Through study treatment, and average of 8 months |
| The Number of Participants Who Experienced Adverse Events (AE) | 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. Safety assessments were performed at baseline and during the study: Vital signs (blood pressure, pulse, temperature), Laboratory (hemoglobin, White Blood Cell, Absolute Neutrophils, platelet count, fasting glucose, alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, serum creatinine, sodium, potassium, magnesium, total calcium. AEs were graded according to NCI-CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 4.03. | Through study treatment, and average of 8 months |
| Overall Change From Baseline Between Treatment Comparison in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Functional Scale Scores | The EORTC QLQ C30 is a 30 item questionnaire composed of functional scales, a global health/quality of life and cancer related symptoms. All of the scales and single-item measures range are scored from 0 to 100. A high scale score represents a high / healthy level of functioning. Change from baseline has been calculated as each visit score minus baseline score. The change from baseline of EORTC QLQ-C30 subscales have been analyzed using linear mixed models, including treatment group, visit, the interaction between treatment group and visit, baseline score and stratification factors as covariates. Overall mean of change and CI 95% has been retrieved from this analysis. | Assessed at Baseline, cycles 3, 5, 7, and then at every 3 cycles until the end of treatment, and at the visit after treatment, an average of 8 months. |
| Overall Change From Baseline Between Treatment Comparison in EORTC QLQ-C30 Symptom Scale Scores | The EORTC QLQ C30 is a 30 item questionnaire composed of functional scales, a global health/quality of life and cancer related symptoms. All of the scales and single-item measures range are scored from 0 to 100. A high scale score represents a high level of symptomatology / problems. Change from baseline has been calculated as each visit score minus baseline score. The change from baseline of EORTC QLQ-C30 subscales have been analyzed using linear mixed models, including treatment group, visit, the interaction between treatment group and visit, baseline score and stratification factors as covariates. Overall mean of change and CI 95% has been retrieved from this analysis. | Assessed at Baseline, cycles 3, 5, 7, and then at every 3 cycles until the end of treatment, and at the visit after treatment, an average of 8 months. |
| Overall Change From Baseline Between Treatment Comparison in European Organization for Research and Treatment of Cancer Breast Cancer Module (EORTC QLQ BR23) Functional Scale Scores | The EORTC QLQ BR23 is a 23 item breast cancer specific companion module to the EORTC QLQ C30 and consists of functional scales and symptom subscales. All of the scales and single-item measures range are scored from 0 to 100. A high score for the functional scales represents a high/healthy level of functioning. Change from baseline has been calculated as each visit score minus baseline score. The change from baseline of EORTC QLQ-BR23 subscales have been analyzed using linear mixed models, including treatment group, visit, the interaction between treatment group and visit, baseline score and stratification factors as covariates. Overall mean of change and CI 95% has been retrieved from this analysis. | Assessed at Baseline, cycles 3, 5, 7, and then at every 3 cycles until the end of treatment, and at the visit after treatment, an average of 8 months. |
| Overall Change From Baseline Between Treatment Comparison in EORTC QLQ BR23 Symptom Scale Scores | The EORTC QLQ BR23 is a 23 item breast cancer specific companion module to the EORTC QLQ C30 and consists of functional scales and symptom subscales. All of the scales and single-item measures range are scored from 0 to 100. A high score for the functional scales represents a high level of symptomatology / problems. Change from baseline has been calculated as each visit score minus baseline score. The change from baseline of EORTC QLQ-BR23 subscales have been analyzed using linear mixed models, including treatment group, visit, the interaction between treatment group and visit, baseline score and stratification factors as covariates. Overall mean of change and CI 95% has been retrieved from this analysis. | Assessed at Baseline, cycles 3, 5, 7, and then at every 3 cycles until the end of treatment, and at the visit after treatment, an average of 8 months. |
| Overall Change From Baseline Between Treatment Comparison in EuroQoL 5D (EQ-5D) Health Index Scores | EQ 5D is a 6 item instrument which assess health status in terms of a single index value. Consists of 5 descriptors of current health state (mobility, self-care, usual activities, pain/discomfort, anxiety/depression); patient is asked to rate each state on 3 level scale (1=no problem, 2=some problem, 3=extreme problem). Higher levels indicating greater severity/impairment. It includes a visual analogue scale (EQ VAS) which records patient's self-rated health on a scale from 0 (worst imaginable) to 100 (best imaginable). Published weights allows for the creation of a single summary score. Overall scores range from 0 to 1 (low score=higher level of dysfunction, 1=perfect health). The change from baseline of EQ-5D subscales have been analyzed using linear mixed models, including treatment group, visit, the interaction between treatment group and visit, baseline score and stratification factors as covariates. Overall mean of change and CI 95% has been retrieved from this analysis. | Assessed at Baseline, cycles 3, 5, 7, and then at every 3 cycles until the end of treatment, and at the visit after treatment. An average of 8 months, an average of 1 year, and an average of 2 years. |
| Overall Change From Baseline Between Treatment Comparison in EQ-5D Visual Analog Scale (VAS) Scores Scale | The EuroQol-5D (version 3L) is a brief self-administered, validated instrument consisting of 2 parts. The second part consists of the EQ-5D general health status as measured by a visual analog scale (EQ-5D VAS). EQ-5D VAS measures the participant's self-rated health status on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state). The change from baseline of EQ-5D subscales have been analyzed using linear mixed models, including treatment group, visit, the interaction between treatment group and visit, baseline score and stratification factors as covariates. Overall mean of change and CI 95% has been retrieved from this analysis. | Assessed at Baseline, cycles 3, 5, 7, and then at every 3 cycles until the end of treatment, and at the visit after treatment. An average of 8 months, an average of 1 year, and an average of 2 years. |
| Time to Deterioration (TTD) in EORTC QLQ-C30 Functional Scale | Time to deterioration is defined as the time from the date of randomization to the date of first detection of deterioration. Deterioration is defined as a change from baseline ≥ minimally important difference (MID) as a change from baseline ≤ -MID for EORTC QLQ-C30 functional scales, global health status/QOL score. Patients without deterioration have been censored at their last quality of life assessment. For patients with no post-baseline assessment time to deterioration have been censored at Day 1. | Assessed at Baseline, cycles 3, 5, 7, and then at every 3 cycles until the end of treatment, and at the visit after treatment, an average of 8 months. |
| Time to Deterioration (TTD) in EORTC QLQ-C30 Symptom Scale | Time to deterioration is defined as the time from the date of randomization to the date of first detection of deterioration. Deterioration is defined as a change from baseline ≥ minimally important difference (MID) for EORTC QLQ-C30 symptom scores. Patients without deterioration have been censored at their last quality of life assessment. For patients with no post-baseline assessment time to deterioration have been censored at Day 1. 999 means value not estimated. | Assessed at Baseline, cycles 3, 5, 7, and then at every 3 cycles until the end of treatment, and at the visit after treatment, an average of 8 months. |
| Time to Deterioration (TTD) in EORTC QLQ-BR23 Functional Scale | Time to deterioration is defined as the time from the date of randomization to the date of first detection of deterioration for QLQ-BR23 score [(date of first detection of deterioration - date of randomization + 1). Deterioration is defined as a change from baseline ≥ minimally important difference (MID) for QLQ-BR23 score. Patients without deterioration have been censored at their last quality of life assessment. For patients with no post-baseline assessment time to deterioration have been censored at Day 1. Sexual functioning and Sexual enjoyment could not be estimated due to lack of response. 999 means value not estimated.](streamdown:incomplete-link) | Assessed at Baseline, cycles 3, 5, 7, and then at every 3 cycles until the end of treatment, and at the visit after treatment, an average of 8 months. |
| Time to Deterioration (TTD) in EORTC QLQ-BR23 Symptom Scale | Time to deterioration is defined as the time from the date of randomization to the date of first detection of deterioration for QLQ-BR23 score [(date of first detection of deterioration - date of randomization + 1). Deterioration is defined as a change from baseline ≥ minimally important difference (MID) for QLQ-BR23 score. Patients without deterioration have been censored at their last quality of life assessment. For patients with no post-baseline assessment time to deterioration have been censored at Day 1. Upset by hair loss could not be estimated due to lack of response.](streamdown:incomplete-link) | Assessed at Baseline, cycles 3, 5, 7, and then at every 3 cycles until the end of treatment, and at the visit after treatment, an average of 8 months. |
| Steyr |
| 4400 |
| Austria |
| Universitätsklinik für Innere Medizin I | Vienna | 1090 | Austria |
| Semmelweis Egyetem | Budapest | 1083 | Hungary |
| Szent Imre Egyetemi Oktatókórház | Budapest | 1115 | Hungary |
| National Institute of Oncology | Budapest | 1122 | Hungary |
| Onkotherápiás Klinika | Szeged | 6720 | Hungary |
| Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Rendelőintézet | Szolnok | 5004 | Hungary |
| Meir Medical Center | Kfar Saba | 44281 | Israel |
| Rabin Medical Center | Petah Tikva | 49100 | Israel |
| Tel Aviv Sourasky Medical Center | Tel Aviv | 64239 | Israel |
| Sheba Medical Center | Tel Litwinsky | 52621 | Israel |
| ICO de L'Hospitalet | L'Hospitalet de Llobregat | Barcelona | 08908 | Spain |
| Complejo Hospitalario Universitario A Coruña | A Coruña | 15006 | Spain |
| Centro Oncológico de Galicia | A Coruña | 15009 | Spain |
| Hospital del Mar | Barcelona | 08003 | Spain |
| Hospital Clinic i Provincial | Barcelona | 08036 | Spain |
| Hospital Universitario Germans Trias i Pujol | Barcelona | 08916 | Spain |
| Hospital San Pedro De Alcántara | Cáceres | 10003 | Spain |
| Complejo Hospitalario Universitario Reina SofÃa | Córdoba | 14004 | Spain |
| Hospital de Donostia | Donostia / San Sebastian | 20014 | Spain |
| Complejo Hospitalario de Jaén | Jaén | 23007 | Spain |
| Hospital de León | León | 24071 | Spain |
| Hospital Universitario Arnau de Vilanova de Lleida | Lleida | 25198 | Spain |
| Hospital Universitario Lucus Augusti | Lugo | 27003 | Spain |
| Hospital General Universitario Gregorio Marañón | Madrid | 28007 | Spain |
| Hospital Universitario 12 de Octubre | Madrid | 28021 | Spain |
| Hospital ClÃnico Universitario San Carlos | Madrid | 28040 | Spain |
| Hospital ClÃnico Universitario Virgen de la Victoria | Málaga | 29010 | Spain |
| Hospital Universitario Virgen de la Arrixaca | Murcia | 30120 | Spain |
| Hospital ClÃnico Universitario de Salamanca | Salamanca | 37007 | Spain |
| Hospital Universitario Virgen del RocÃo | Seville | 41013 | Spain |
| Hospital Virgen de La Salud | Toledo | 45004 | Spain |
| Hospital ClÃnico Universitario de Valencia | Valencia | 46010 | Spain |
| Hospital Universitario La Fe | Valencia | 46026 | Spain |
| Hospital ClÃnico Universitario de Zaragoza "Lozano Blesa" | Zaragoza | 50009 | Spain |
| Hospital Universitario Miguel Servet | Zaragoza | 50009 | Spain |
| Result |
| Martin M, Zielinski C, Ruiz-Borrego M, Carrasco E, Ciruelos EM, Munoz M, Bermejo B, Margeli M, Csoszi T, Anton A, Turner N, Casas MI, Morales S, Alba E, Calvo L, de la Haba-Rodriguez J, Ramos M, Murillo L, Santaballa A, Alonso-Romero JL, Sanchez-Rovira P, Corsaro M, Huang X, Thallinger C, Kahan Z, Gil-Gil M. Overall survival with palbociclib plus endocrine therapy versus capecitabine in postmenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer in the PEARL study. Eur J Cancer. 2022 Jun;168:12-24. doi: 10.1016/j.ejca.2022.03.006. Epub 2022 Apr 13. |
| 34425406 | Result | Kahan Z, Gil-Gil M, Ruiz-Borrego M, Carrasco E, Ciruelos E, Munoz M, Bermejo B, Margeli M, Anton A, Casas M, Csoszi T, Murillo L, Morales S, Calvo L, Lang I, Alba E, de la Haba-Rodriguez J, Ramos M, Lopez IA, Gal-Yam E, Garcia-Palomo A, Alvarez E, Gonzalez-Santiago S, Rodriguez CA, Servitja S, Corsaro M, Rodrigalvarez G, Zielinski C, Martin M. Health-related quality of life with palbociclib plus endocrine therapy versus capecitabine in postmenopausal patients with hormone receptor-positive metastatic breast cancer: Patient-reported outcomes in the PEARL study. Eur J Cancer. 2021 Oct;156:70-82. doi: 10.1016/j.ejca.2021.07.004. Epub 2021 Aug 20. |
| 36749874 | Result | Guerrero-Zotano A, Belli S, Zielinski C, Gil-Gil M, Fernandez-Serra A, Ruiz-Borrego M, Ciruelos Gil EM, Pascual J, Munoz-Mateu M, Bermejo B, Margeli Vila M, Anton A, Murillo L, Nissenbaum B, Liu Y, Herranz J, Fernandez-Garcia D, Caballero R, Lopez-Guerrero JA, Bianco R, Formisano L, Turner N, Martin M. CCNE1 and PLK1 Mediate Resistance to Palbociclib in HR+/HER2- Metastatic Breast Cancer. Clin Cancer Res. 2023 Apr 14;29(8):1557-1568. doi: 10.1158/1078-0432.CCR-22-2206. |
Cohort 1: 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. Capecitabine |
| FG002 | Cohort 2: Palbociclib Plus Fulvestrant | Cohort 2: 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 Fulvestrant 500 mg on Days 1 and 15 of Cycle 1, and Day 1 of each subsequent 28 days Cycle. Palbociclib Fulvestrant |
| FG003 | Cohort 2: Capecitabine | Cohort 2: 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. Capecitabine |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1: Palbociclib Plus Exemestane | - Cohort 1: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 Exemestane 25 mg orally once daily. Palbociclib Exemestane |
| BG001 | Cohort 1:Capecitabine | Cohort 1: 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. Capecitabine |
| BG002 | Cohort 2: Palbociclib Plus Fulvestrant | - Cohort 2: 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 Fulvestrant 500 mg on Days 1 and 15 of Cycle 1, and Day 1 of each subsequent 28 days Cycle. Palbociclib Fulvestrant |
| BG003 | Cohort 2:Capecitabine | Cohort 2: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. Capecitabine |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||
| Eastern Cooperative Oncology Group (ECOG) status | ECOG score runs from 0 to 5, with 0 denoting perfect health and 5 death. 0 - Asymptomatic
| Count of Participants | Participants |
| |||||||||||||||
| Visceral disease | Count of Participants | Participants |
| ||||||||||||||||
| Hormone receptor status | Count of Participants | Participants |
| ||||||||||||||||
| ESR1 mutational status | Count of Participants | Participants |
| ||||||||||||||||
| Sensitivity to prior endocrine therapy | Count of Participants | Participants |
| ||||||||||||||||
| Number of prior lines of endocrine therapy for metastatic breast cancer (MBC) | Count of Participants | Participants |
| ||||||||||||||||
| Prior chemotherapy for MBC | Count of Participants | Participants |
| ||||||||||||||||
| Line at study entry | Count of Participants | Participants |
| ||||||||||||||||
| Status at initial diagnosis | Count of Participants | Participants |
| ||||||||||||||||
| Histopathology type | Count of Participants | Participants |
| ||||||||||||||||
| Histologic grade | Cancer cells are given a Grade (G) when they are removed from the breast and checked under a microscope. The G is based on how much the cancer cells look like normal cells. G1 or well differentiated (score 3, 4, or 5): cells are slower-growing, and look more like normal breast tissue. G2 or moderately differentiated (score 6, 7): cells are growing at a speed of and look like cells somewhere between G1 and 3. G3 or poorly differentiated (score 8, 9): cells look very different from normal and will probably grow and spread faster. | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Progression-Free Survival (PFS) | 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. Disease assessments will be performed at baseline and every 8 weeks (± 7 days) from the start of treatment and every 12 weeks (±7 days) after 120 weeks of treatment 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. | The Intent to treat population (ITT) include all patients who were randomized, with study drug/medication assignment designated according to initial randomization. | Posted | Median | 95% Confidence Interval | month | Through study treatment, and average of 8 months |
|
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| Secondary | PFS Estrogen Receptor 1 (ESR1) Wild Type | 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. PFS data will be censored on the date of the last tumor assessment on study for patients who do not have objective tumor progression and who do not die while on study. Patients lacking an evaluation of tumor response after randomization will have their PFS time censored on the date of randomization with 1 day duration. Additionally, patients who start a new anti-cancer therapy prior to documented PD will be censored at the date of the last tumor assessment prior to the start of the new therapy. | ESR1 wild type population include patients with ESR1 mutational status as wild type at study entry.
| Posted | Median | 95% Confidence Interval | months | From randomization date to date of first documentation of progression or death (an average of 8 months) |
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| Secondary | Overall Survival (OS) ESR1 Wild Type | OS is defined as the time from the date of randomization to the date of death from any cause. | ESR1 wild type population include patients with ESR1 mutational status as wild type at study entry.
| Posted | Median | 95% Confidence Interval | months | From randomization until death (up to approximately 34 months) |
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| Secondary | Objective Response Rate (ORR) ESR1 Wild Type | 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. | ESR1 wild type population include patients with ESR1 mutational status as wild type at study entry.
| Posted | Count of Participants | Participants | Through study treatment, and average of 8 months |
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| Secondary | Clinical Benefit Rate (CBR) ESR1 Wild Type | 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). Per RECIST, CR is defined as the disappearance of all target lesions; PR is defined as an >=30% decrease in the sum of the longest diameter of target lesions; SD is defined as a failure to meet criteria for CR or PR in the absence of progressive disease. Overall Response (OR) = CR + PR. | ESR1 wild type population include patients with ESR1 mutational status as wild type at study entry.
| Posted | Count of Participants | Participants | Through study treatment, and average of 8 months |
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| Secondary | Response Duration (RD) ESR1 Wild Type | Tumor response was assessed using Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria. RD was defined as the time from the first documentation of objective tumor response (complete response (CR) or partial response (PR)) to the first documented progressive disease (PD), or to death due to any cause, whichever occurs first. Per RECIST, CR is defined as the disappearance of all target lesions; PR is defined as an >=30% decrease in the sum of the longest diameter of target lesions; PD is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions | Safety population includes all patients randomized in the study who received at least one dose of treatment, according to the actual treatment received. Patients from Safety Population with Measurable Disease and Best Response Complete or Partial. | Posted | Median | 95% Confidence Interval | months | Through study treatment, and average of 8 months |
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| Secondary | The Number of Participants Who Experienced Adverse Events (AE) | 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. Safety assessments were performed at baseline and during the study: Vital signs (blood pressure, pulse, temperature), Laboratory (hemoglobin, White Blood Cell, Absolute Neutrophils, platelet count, fasting glucose, alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, serum creatinine, sodium, potassium, magnesium, total calcium. AEs were graded according to NCI-CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 4.03. | Safety population include patients randomized in the study who received at least one dose of treatment, according to the actual treatment received. | Posted | Count of Participants | Participants | Through study treatment, and average of 8 months |
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| Secondary | Overall Change From Baseline Between Treatment Comparison in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Functional Scale Scores | The EORTC QLQ C30 is a 30 item questionnaire composed of functional scales, a global health/quality of life and cancer related symptoms. All of the scales and single-item measures range are scored from 0 to 100. A high scale score represents a high / healthy level of functioning. Change from baseline has been calculated as each visit score minus baseline score. The change from baseline of EORTC QLQ-C30 subscales have been analyzed using linear mixed models, including treatment group, visit, the interaction between treatment group and visit, baseline score and stratification factors as covariates. Overall mean of change and CI 95% has been retrieved from this analysis. | QoL population: a subset of enrolled patients with available QoL questionnaires (the baseline and at least one more). | Posted | Mean | 95% Confidence Interval | units on a scale | Assessed at Baseline, cycles 3, 5, 7, and then at every 3 cycles until the end of treatment, and at the visit after treatment, an average of 8 months. |
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| Secondary | Overall Change From Baseline Between Treatment Comparison in EORTC QLQ-C30 Symptom Scale Scores | The EORTC QLQ C30 is a 30 item questionnaire composed of functional scales, a global health/quality of life and cancer related symptoms. All of the scales and single-item measures range are scored from 0 to 100. A high scale score represents a high level of symptomatology / problems. Change from baseline has been calculated as each visit score minus baseline score. The change from baseline of EORTC QLQ-C30 subscales have been analyzed using linear mixed models, including treatment group, visit, the interaction between treatment group and visit, baseline score and stratification factors as covariates. Overall mean of change and CI 95% has been retrieved from this analysis. | QoL population: a subset of enrolled patients with available QoL questionnaires (the baseline and at least one more). | Posted | Mean | 95% Confidence Interval | units on a scale | Assessed at Baseline, cycles 3, 5, 7, and then at every 3 cycles until the end of treatment, and at the visit after treatment, an average of 8 months. |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Overall Change From Baseline Between Treatment Comparison in European Organization for Research and Treatment of Cancer Breast Cancer Module (EORTC QLQ BR23) Functional Scale Scores | The EORTC QLQ BR23 is a 23 item breast cancer specific companion module to the EORTC QLQ C30 and consists of functional scales and symptom subscales. All of the scales and single-item measures range are scored from 0 to 100. A high score for the functional scales represents a high/healthy level of functioning. Change from baseline has been calculated as each visit score minus baseline score. The change from baseline of EORTC QLQ-BR23 subscales have been analyzed using linear mixed models, including treatment group, visit, the interaction between treatment group and visit, baseline score and stratification factors as covariates. Overall mean of change and CI 95% has been retrieved from this analysis. | QoL population: a subset of enrolled patients with available QoL questionnaires (the baseline and at least one more). | Posted | Mean | 95% Confidence Interval | units on a scale | Assessed at Baseline, cycles 3, 5, 7, and then at every 3 cycles until the end of treatment, and at the visit after treatment, an average of 8 months. |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Overall Change From Baseline Between Treatment Comparison in EORTC QLQ BR23 Symptom Scale Scores | The EORTC QLQ BR23 is a 23 item breast cancer specific companion module to the EORTC QLQ C30 and consists of functional scales and symptom subscales. All of the scales and single-item measures range are scored from 0 to 100. A high score for the functional scales represents a high level of symptomatology / problems. Change from baseline has been calculated as each visit score minus baseline score. The change from baseline of EORTC QLQ-BR23 subscales have been analyzed using linear mixed models, including treatment group, visit, the interaction between treatment group and visit, baseline score and stratification factors as covariates. Overall mean of change and CI 95% has been retrieved from this analysis. | QoL population: a subset of enrolled patients with available QoL questionnaires (the baseline and at least one more). | Posted | Mean | 95% Confidence Interval | units on a scale | Assessed at Baseline, cycles 3, 5, 7, and then at every 3 cycles until the end of treatment, and at the visit after treatment, an average of 8 months. |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Overall Change From Baseline Between Treatment Comparison in EuroQoL 5D (EQ-5D) Health Index Scores | EQ 5D is a 6 item instrument which assess health status in terms of a single index value. Consists of 5 descriptors of current health state (mobility, self-care, usual activities, pain/discomfort, anxiety/depression); patient is asked to rate each state on 3 level scale (1=no problem, 2=some problem, 3=extreme problem). Higher levels indicating greater severity/impairment. It includes a visual analogue scale (EQ VAS) which records patient's self-rated health on a scale from 0 (worst imaginable) to 100 (best imaginable). Published weights allows for the creation of a single summary score. Overall scores range from 0 to 1 (low score=higher level of dysfunction, 1=perfect health). The change from baseline of EQ-5D subscales have been analyzed using linear mixed models, including treatment group, visit, the interaction between treatment group and visit, baseline score and stratification factors as covariates. Overall mean of change and CI 95% has been retrieved from this analysis. | QoL population: a subset of enrolled patients with available QoL questionnaires (the baseline and at least one more). | Posted | Mean | 95% Confidence Interval | units on a scale | Assessed at Baseline, cycles 3, 5, 7, and then at every 3 cycles until the end of treatment, and at the visit after treatment. An average of 8 months, an average of 1 year, and an average of 2 years. |
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| Secondary | Overall Change From Baseline Between Treatment Comparison in EQ-5D Visual Analog Scale (VAS) Scores Scale | The EuroQol-5D (version 3L) is a brief self-administered, validated instrument consisting of 2 parts. The second part consists of the EQ-5D general health status as measured by a visual analog scale (EQ-5D VAS). EQ-5D VAS measures the participant's self-rated health status on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state). The change from baseline of EQ-5D subscales have been analyzed using linear mixed models, including treatment group, visit, the interaction between treatment group and visit, baseline score and stratification factors as covariates. Overall mean of change and CI 95% has been retrieved from this analysis. | QoL population: a subset of enrolled patients with available QoL questionnaires (the baseline and at least one more). | Posted | Mean | 95% Confidence Interval | units on a scale | Assessed at Baseline, cycles 3, 5, 7, and then at every 3 cycles until the end of treatment, and at the visit after treatment. An average of 8 months, an average of 1 year, and an average of 2 years. |
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| Secondary | Time to Deterioration (TTD) in EORTC QLQ-C30 Functional Scale | Time to deterioration is defined as the time from the date of randomization to the date of first detection of deterioration. Deterioration is defined as a change from baseline ≥ minimally important difference (MID) as a change from baseline ≤ -MID for EORTC QLQ-C30 functional scales, global health status/QOL score. Patients without deterioration have been censored at their last quality of life assessment. For patients with no post-baseline assessment time to deterioration have been censored at Day 1. | QoL population: a subset of enrolled patients with available QoL questionnaires (the baseline and at least one more). | Posted | Median | 95% Confidence Interval | months | Assessed at Baseline, cycles 3, 5, 7, and then at every 3 cycles until the end of treatment, and at the visit after treatment, an average of 8 months. |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Time to Deterioration (TTD) in EORTC QLQ-C30 Symptom Scale | Time to deterioration is defined as the time from the date of randomization to the date of first detection of deterioration. Deterioration is defined as a change from baseline ≥ minimally important difference (MID) for EORTC QLQ-C30 symptom scores. Patients without deterioration have been censored at their last quality of life assessment. For patients with no post-baseline assessment time to deterioration have been censored at Day 1. 999 means value not estimated. | QoL population: a subset of enrolled patients with available QoL questionnaires (the baseline and at least one more). NA (Not Available): the statistical program has not been able to estimate the upper limit of the interval because of the lower number of participants answering the applicable questions. | Posted | Median | 95% Confidence Interval | months | Assessed at Baseline, cycles 3, 5, 7, and then at every 3 cycles until the end of treatment, and at the visit after treatment, an average of 8 months. |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Time to Deterioration (TTD) in EORTC QLQ-BR23 Functional Scale | Time to deterioration is defined as the time from the date of randomization to the date of first detection of deterioration for QLQ-BR23 score [(date of first detection of deterioration - date of randomization + 1). Deterioration is defined as a change from baseline ≥ minimally important difference (MID) for QLQ-BR23 score. Patients without deterioration have been censored at their last quality of life assessment. For patients with no post-baseline assessment time to deterioration have been censored at Day 1. Sexual functioning and Sexual enjoyment could not be estimated due to lack of response. 999 means value not estimated.](streamdown:incomplete-link) | QoL population: a subset of enrolled patients with available QoL questionnaires (the baseline and at least one more). | Posted | Median | 95% Confidence Interval | months | Assessed at Baseline, cycles 3, 5, 7, and then at every 3 cycles until the end of treatment, and at the visit after treatment, an average of 8 months. |
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| Secondary | Time to Deterioration (TTD) in EORTC QLQ-BR23 Symptom Scale | Time to deterioration is defined as the time from the date of randomization to the date of first detection of deterioration for QLQ-BR23 score [(date of first detection of deterioration - date of randomization + 1). Deterioration is defined as a change from baseline ≥ minimally important difference (MID) for QLQ-BR23 score. Patients without deterioration have been censored at their last quality of life assessment. For patients with no post-baseline assessment time to deterioration have been censored at Day 1. Upset by hair loss could not be estimated due to lack of response.](streamdown:incomplete-link) | QoL population: a subset of enrolled patients with available QoL questionnaires (the baseline and at least one more). | Posted | Median | 95% Confidence Interval | months | Assessed at Baseline, cycles 3, 5, 7, and then at every 3 cycles until the end of treatment, and at the visit after treatment, an average of 8 months. |
|
Through study treatment, an average of 8 months. All-Cause Mortality, through study treatment and follow up to approximately 34 months.
AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation of study treatment.
All-Cause Mortality were reported from randomization until death (up to approximately 34 months).
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1: Palbociclib Plus Exemestane | Cohort 1: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 Exemestane 25 mg orally once daily. Palbociclib Exemestane | 85 | 150 | 34 | 150 | 147 | 150 |
| EG001 | Cohort 2: Palbociclib Plus Fulvestrant | Cohort 2: 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 Fulvestrant 500 mg on Days 1 and 15 of Cycle 1, and Day 1 of each subsequent 28 days Cycle. Palbociclib Fulvestrant | 43 | 149 | 21 | 149 | 148 | 149 |
| EG002 | Cohort 1 and 2: 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. Capecitabine | 116 | 289 | 72 | 289 | 286 | 289 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Acidosis | Metabolism and nutrition disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Anemia | Blood and lymphatic system disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Bile duct stenosis | Hepatobiliary disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Bone fracture | Musculoskeletal and connective tissue disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Breast infection | Infections and infestations | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Bronchial infection | Infections and infestations | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Burn | Injury, poisoning and procedural complications | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Catheter related infection | Infections and infestations | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Chest pain - cardiac | Cardiac disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Fatigue | General disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Fever | General disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Gallbladder infection | Infections and infestations | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Ileitis | Gastrointestinal disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Headache | Nervous system disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Heart failure | Cardiac disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Hematoma | Vascular disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Biliary colic | Hepatobiliary disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Cholecystitis acute | Hepatobiliary disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Hypercalcemia | Metabolism and nutrition disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Hypokalemia | Metabolism and nutrition disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Bacteremia | Infections and infestations | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Erysipelas | Infections and infestations | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Gastrointestinal infection | Infections and infestations | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Respiratory infection | Infections and infestations | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Dislocation of hip | Injury, poisoning and procedural complications | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Drug overdose | Injury, poisoning and procedural complications | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Ischemia cerebrovascular | Nervous system disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Lung infection | Infections and infestations | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Lymphedema | Vascular disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Malaise | General disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Mucositis | Gastrointestinal disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Chronic myeloid leukemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Second primary malignancy | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Urinary bladder carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Spinal cord compression | Nervous system disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Osteonecrosis of jaw | Musculoskeletal and connective tissue disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Palmar-plantar erythrodysesthesia syndrome | Skin and subcutaneous tissue disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Platelet count decreased | Blood and lymphatic system disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Hydronephrosis | Renal and urinary disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Asthma | Respiratory, thoracic and mediastinal disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Hemoptysis | Respiratory, thoracic and mediastinal disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Seroma | Injury, poisoning and procedural complications | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Stroke | Nervous system disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Suicide attempt | Psychiatric disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Hip replacement | Surgical and medical procedures | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Thromboembolic event | Vascular disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Tooth infection | Infections and infestations | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Typhlitis | Gastrointestinal disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Upper respiratory infection | Infections and infestations | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Uveitis | Eye disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatigue | General disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Neutrophil count decreased | Blood and lymphatic system disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Palmar-plantar erythrodysesthesia syndrome | Skin and subcutaneous tissue disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Mucositis | Skin and subcutaneous tissue disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Weight loss | Investigations | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Weight gain | Investigations | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Anorexia | Metabolism and nutrition disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Hypothermia | General disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Headache | Nervous system disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Upper respiratory infection | Respiratory, thoracic and mediastinal disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Nail disorder | Skin and subcutaneous tissue disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Fever | General disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Obesity | Metabolism and nutrition disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Anemia | Blood and lymphatic system disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Flu like symptoms | General disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Pain | General disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
| |
| Hot flashes | Vascular disorders | NCI CTC-AE v 4.03 | Systematic Assessment |
|
Potential limitations of the study are:
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 30 days but less than or equal to 180 days from the time submitted to the sponsor for review. The sponsor can require changes to the communication.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Scientific Director / Medical Lead / Project Manager | Spanish Breast Cancer Research Group | +34916592870 | geicam@geicam.org |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 31, 2017 | Feb 16, 2021 | SAP_001.pdf |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C500026 | palbociclib |
| D000069287 | Capecitabine |
| C056516 | exemestane |
| D000077267 | Fulvestrant |
| ID | Term |
|---|---|
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D005472 | Fluorouracil |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D004958 | Estradiol |
| D004963 | Estrenes |
| D004962 | Estranes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D045166 | Estradiol Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Not Hispanic Or Latino |
|
| Unknown |
|
| Hungary |
|
| Israel |
|
| Spain |
|
| ECOG 1 |
|
| No |
|
| Not available |
|
| ER positive and PR negative |
|
| ER negative and PR positive or ER positive and PR not available |
|
| Triple negative |
|
| Mutant |
|
| Not available |
|
| No |
|
| 1 |
|
| 2 |
|
| 3 |
|
| Maintenance after chemotherapy |
|
| Combination |
|
| No |
|
| 2nd line |
|
| ≥3rd line |
|
| M1: Cancer has spread to other parts of the body |
|
| Breast Invasive Lobular Carcinoma |
|
| Other |
|
| Not Available/Not Done |
|
| G2, Moderately Differentiated |
|
| G3, Poorly Differentiated |
|
| GX, Unknown |
|
| Not Available/Not Done |
|
| OG001 | Capecitabine ESR1 Wild Type Population | The ESR1 wild type population will include all patients who are randomized, with study drug/medication assignment designated according to initial randomization and whose tumor had estrogen receptor (ESR1) mutational status as wild type at study entry. |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
The ESR1 wild type population will include all patients who are randomized, with study drug/medication assignment designated according to initial randomization and whose tumor had estrogen receptor (ESR1) mutational status as wild type at study entry. |
|
|
The ESR1 wild type population include all patients who are randomized, with study drug/medication assignment designated according to initial randomization and whose tumor had estrogen receptor (ESR1) mutational status as wild type at study entry. |
|
|
The ESR1 wild type population will include all patients who are randomized, with study drug/medication assignment designated according to initial randomization and whose tumor had estrogen receptor (ESR1) mutational status as wild type at study entry.
|
|
| OG002 | Cohort 1 + 2: Capecitabine | Cohort 1 and 2: 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. Capecitabine |
|
|
| OG001 | Cohort 1 and 2: 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. Capecitabine |
|
|
| OG001 |
| Cohort 1 and 2: 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. Capecitabine |
|
|
| OG001 | Cohort 1 and 2: 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. Capecitabine |
|
|
| OG001 |
| Cohort 1 and 2: 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. Capecitabine |
|
|
| OG001 | Cohort 1 and 2: 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. Capecitabine |
|
|
| OG001 | Cohort 1 and 2: 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. 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. 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. 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.
Capecitabine
|
|
|