A randomized, multicentre, open-label, phase II trial to evaluate the efficacy and safety of palbociclib in combination with fulvestrant or letrozole in patients with HER2 negative, ER+ metastatic breast cancer.
- Conditions
- Metastatic breast cancerTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-004698-17-GB
- Lead Sponsor
- Medica Scientia Innovation Research (MedSIR)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 486
1. Postmenopausal women, as defined by any of the following criteria:
- Age 60 or over
- Age 45 to 59 years and meets = 1 of the following criteria:
- Amenorrhea for = 24 months
- Amenorrhea for < 24 months and follicle-stimulating hormone
within the postmenopausal range (including patients with hysterectomy,
prior hormone replacement therapy, or chemotherapy-induced
amenorrhea)
- Over 18 years of age and bilateral oophorectomy
OR
Premenopausal women provided they are being treated with LHRH
analogues for at least 28 days prior to study entry
2. Eastern Cooperative Oncology Group (ECOG) score lower or equal to 2
3. Histologically confirmed recurrent ER positive (oestrogen and/or progesterone) HER2-negative locally advanced or metastatic BC patients (Breast cancer that have at least 1% of cells staging positive for ER should be considered ER-positive according to NCCN and ASCO guidelines).
4. Patients should not be candidates for a local treatment with a radical intention.
5. No prior hormonal or chemotherapy line in the metastatic setting.
6. Patient must have measurable (according to RECIST 1.1) or non measurable disease with these exceptions
- Patients with only blastic bone lesions are not eligible
- Patients with only pleural, peritoneal or cardiac effusion, or meningeal carcinomatosis are not eligible
7. Life expectancy grater or equal to 12 weeks
8. Adequate organ function:
- Hematological: White blood cell (WBC) count >3.0 x 109/L, absolute neutrophil count (ANC) >1.0 x 109/L, platelet count >75.0 x109/L, and hemoglobin >10.0 g/dL (>6.2 mmol/L)
- Hepatic: bilirubin < 1.5 times the upper limit of normal (x ULN); alkaline phosphatase (ALP), aspartate transaminase (AST), and alanine transaminase (ALT) <2.5 times ULN. Patients with ALP =2.5 times ULN
are eligible if ALP abnormalities are unequivocally related to bone
lesions (radiological assessments performed within 4 weeks prior to
randomization demonstrated bone metastatic disease).
- Renal: serum creatinine < 1.5 x ULN.
9. Exhibit patient compliance and geographic proximity that allow for adequate follow-up.
10. Patient has been informed about the nature of study, and has agreed to participate in the study, and signed the Informed Consent form prior to participation in any study-related activities.
11. No other malignancies within the past five years except adequate treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
12. Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCICTCAE version 4.0 Grade =1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion).
13. Patient has been informed about the translational sub-study and has
agreed to participate in the collection of blood and tumor tissue samples by
signing the Informed Consent form.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 166
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 320
Patients will be excluded from the study if they meet ANY of the following criteria:
1. ER or HER2 unknown disease
2. HER2 positive disease based on local laboratory results (performed by immunohistochemistry/FISH)
3. Locally advanced breast cancer candidate for a radical treatment.
4. Prior endocrine therapy in the metastatic setting. (Neo)/Adjuvant endocrine therapy is allowed only if the disease-free interval between the end of endocrine therapy and the appearance of metastases in higher than 12 months.
5. Patients with rapidly progressive visceral disease or visceral crisis.
6. Have had a major surgery (defined as requiring general anaesthesia) or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery or patients that may require major surgery during the course of the study.
7. Patients with an active, bleeding diathesis.
8. Have a serious concomitant systemic disorder (e.g. active infection including HIV, or cardiac disease) incompatible with the study (at the discretion of investigator), previous history of bleeding diathesis, or anti-coagulation treatment (The use of low molecular weight heparin is allowed as long as it is used as prophylaxis).
9. Are unable to swallow tablets.
10. History of malabsorption syndrome or other condition that would interfere with enteral absorption.
11. Chronic daily treatment with corticosteroids with a dose of = 10mg/day methylprednisolone equivalent (excluding inhaled steroids).
12. Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral oedema, 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 (e.g., radiotherapy, stereotactic surgery) and are clinically stable off anticonvulsants and steroids for at least 4weeks before randomization
13. Known hypersensitivity to letrozole, fulvestrant or any of their excipients, or to any PD-0332991 excipients.
14. QTc >480 msec on basal assessments, personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes (TdP).
15. Uncontrolled electrolyte disorders that can compound the effects of a QTc-prolonging drug (e.g., hypocalcemia, hypokalemia, hypomagnesemia).
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