A study for patients with metastatic breast cancer (hormone receptor-positive, negative HER2 and resistance to aromatase inhibidors) comparing palbociclib + exemestane versus capecitabine.
- Conditions
- Patients with hormonal receptor positive and HER2 negative MBC who are resistant to prior aromatase inhibitors therapy.MedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-003170-27-AT
- Lead Sponsor
- GEICAM (Fundación Grupo Español de Investigación en Cáncer de Mama)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 596
1.The patient has signed the informed consent document.
2.a) Patients included in Cohort 1: Females with histologically confirmed MBC whose disease is resistant to previous non-steroidal aromatase inhibitors (letrozole or anastrozole), defined as:
- Recurrence while on or within 12 months after the end of adjuvant treatment with NSAI or
- Progression while on or within 1 month after the end of treatment with NSAI for advanced disease.
b) Patients included in Cohort 2: Females with histologically confirmed MBC whose disease was resistant to previous aromatase inhibitors (exemestane, letrozole or anastrozole), defined as: Recurrence while on or within 12 months after the end of adjuvant treatment with an AI or Progression while on or within 1 month after the end of treatment with an AI for advanced disease.
3.Previous chemotherapy is permitted either in the (neo)adjuvant setting and/or first line therapy for MBC.
4.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 after the end of (in the mestastatic setting immediately after the end of) the most recent systemic therapy has to be documented before randomization.
5.Hormonal receptor positive (HR+) breast cancer based on local laboratory determination. HR+ defined as > or = 1% positive cells by IHC for ER and/or PgR.
6.Documented HER2 negative breast cancer based on local laboratory determination on most recent tumor biopsy. HER2 negative tumor is determined according to the most current recommendations of ASCO/CAP guidelines (2013), as IHC score 0 or 1+ or negative by ISH (FISH/CISH/SISH) defined as a HER2/CEP17 ratio < 2 with an average HER2 copy number <4.0, or for single probe assessment a HER2 copy number < 4.
7.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.
8.Patient is at least 18 years of age.
9.Eastern Cooperative Oncology Group (ECOG) Performance Status < or = 1.
10.Life expectancy > or = 12 weeks.
11.Adequate organ and bone marrow function defined as follows:
- ANC > or = 1,500/mm3 (1.5x109/L)
- Platelets > or = 100,000/mm3 (100x109/L)
- Hemoglobin > or = 9g/dL (90g/L)
- Serum creatinine < or = 1,5xULN or estimated creatinine clearance > or = 60 mL/min as calculated using the standard method for the institution
- Total serum bilirubin < or = 1,5xULN (< or = 3.0xULN if Gilbert´s disease)
- AST and ALT < or = 3.0xULN (< or = 5.0xULN if liver metastases present)
- Alkaline phosphatase < or = 2.5xULN (< or = 5.0xULN if bone or liver metastases present)
12.Postmenopausal women defined as women with: -Prior bilateral surgical oophorectomy, or -Age > 60 years
-Age < 60 year 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
13.Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI CTCAE version 4.0 Grade < or = 1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator´s discretion).
14.Willingness and ability to comply with scheduled
1. Have received more than 1 prior chemotherapy regimen for MBC. NOTE: Other previous anticancer endocrine treatments for advanced disease are allowed.
2. 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).
3. Known active uncontrolled or symptomatic 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, stereotactic surgery) and are clinically stable off anticonvulsants and steroids for at least 4 weeks before randomization.
4. 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.
5.
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: - She has received letrozole/anastrozole as first-line MBC and progressed. - At least 1 year has elapsed since the end of adjuvant exemestane treatment. b) Patients included in Cohort 2: Prior treatment with fulvestrant in the metastatic setting. If the patient has received fulvestrant in the adjuvant setting and developed MBC, she will be eligible for the study provided: - She has received letrozole/anastrozole/exemestane as first-line MBC and progressed. - At least 1 year has elapsed since the end of adjuvant fulvestrant treatment.
6. Patients treated within the last 7 days prior to randomization with:
- Food or drugs that are known to be CYP3A4 inhibitors
- Drugs that are known to be CYP3A4 inducers
- Drugs that are known to prolong the QT interval
7. Major surgery, chemotherapy, radiotherapy, any investigational agent or other anti-cancer therapy within 4 weeks before randomization. Patients who received prior radiotherapy to > or = 25% of bone marrow are not eligible independent of when it was received.
8. 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.
9. QTc > 480msec (based on the mean value of the triplicate ECGs), family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes (TdP).
10. Uncontrolled electrolyte disorders that can compound the effects of a QTc-prolonging drug (eg, hypocalcemia, hypokalemia, hypomagnesemia).
......... 13. Known hypersensitivity to palbociclib, capecitabine, fulvestrant or to exemestane (patients of cohort 1) or to fulvestrant (patients of cohort 2) or any of their excipients.
15.Only for patients in Cohort 2 any of the following contraindications for treatment with fulvestrant: Bleeding diathesis (i.e., disseminated intravascular coagulation [DIC], clotting factor deficiency) or long-term (> 6 months) anticoagulant therapy (other than antiplatelet therapy and low dose coumarin derivatives, provided that the International Normalised Ratio (INR) is less than 1.6.). Please, to see all Principal exclusión criteria, refer to the Prot
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method