A multicenter, international, trial to identify the molecular mechanisms of resistance and sensitivity to palbociclib re-challenge upon progression after a treatment with a palbociclib combination in metastatic breast cancer patients with positive estrogen receptor
- Conditions
- Hormone receptor (HR)-positive/HER2-negative locally advanced or metastatic breast cancer (mBC). Second/third-line of endocrine treatment.MedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-003892-31-IT
- Lead Sponsor
- MEDICA SCIENTIA INNOVATION RESEARCH S.L.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 33
1.Female patients over 18 years of age.
2.Premenopausal women provided they are being treated with LHRH analogues for at least 28 days prior to study entry or postmenopausal women, as defined by any of the following criteria:
a.Age 60 or over.
b.Age 45 to 59 years and meets =1 of the following criteria:
i.Amenorrhea for =24 months.
ii.Amenorrhea for <24 months and follicle-stimulating hormone within the postmenopausal range (including patients with hysterectomy, prior hormone replacement therapy, or chemotherapy-induced amenorrhea).
c.Patients with bilateral oophorectomy.
3.Eastern Cooperative Oncology Group (ECOG) score lower or equal to 1.
4.Life expectancy greater or equal to 12 weeks.
5.Histologically confirmed recurrent HR-positive (ER and/or PR) and HER2-negative locally advanced or mBC patients. (Breast cancer that has at least 1% of cells staging positive for ER and PR should be considered ER-positive and PR-positive according to NCCN and ASCO guidelines).
6.Confirmed disease progression on immediate previous palbociclib plus endocrine therapy.
7.Last dose of palbociclib administered no later than eight weeks and not earlier than three weeks from study entry.
8.Patients must have been treated with a stable dose of palbociclib of a minimum dose level of 100 mg/day during the last four weeks in the previous palbociclib line.
9.Patients achieved clinical benefit criteria to previous palbociclib-based regimen (defined as at least stable disease =24 weeks or partial or complete response).
10.No prior use of at least one of the reasonable endocrine therapy options: tamoxifen, fulvestrant, letrozole/anastrozole, or exemestane.
11.Patients must have measurable disease (according to RECIST v.1.1).
12.Patients agree to collection of blood samples (liquid biopsy) and collection of metastatic tumour sample (biopsy) at the time of inclusion and progression (if appropriate).
13.No more than two prior lines of endocrine therapy for metastatic disease.
14.No more than one prior line of chemotherapy for advanced disease.
15.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. Note: 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.
16.Exhibit patient compliance and geographic proximity that allow for adequate follow-up.
17.Patients have been informed about the nature of study, and have agreed to participate in the study, and signed the informed consent form prior to participation in any study-related activities.
18.Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to grade minor or equal to 1 as determined by the National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) v.4.0.3 (except alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion).
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
1.HR or HER2 unknown disease.
2.HER2-positive disease based on local laboratory results [performed by immunohistochemistry/fluorescence in situ hybridization (FISH)].
3.Locally advanced breast cancer candidate for a local treatment with a radical intention.
4.Formal contraindication to endocrine therapy.
5.Progressing central nervous system (CNS) disease.
6.Patients with exclusive non-measurable/evaluable disease.
7.Other malignancies within the past five years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix.
8.Major surgery (defined as requiring general anaesthesia) or significant traumatic injury within four weeks of start of study drug, or 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.
9.Patients with an active bleeding diathesis, previous history of bleeding diathesis, or anti-coagulation treatment (the use of low molecular weight heparin is allowed as soon as it is used as prophylaxis intention).
10.Have a serious concomitant systemic disorder (i.e., active infection including HIV, or cardiac disease) incompatible with the study (at the discretion of investigator).
11.Are unable to swallow tablets.
12.History of malabsorption syndrome or other condition that would interfere with enteral absorption.
13.Chronic daily treatment with corticosteroids with a dose of =10 mg/day methylprednisolone equivalent (excluding inhaled steroids).
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 (i.e., hypocalcemia, hypokalemia, or hypomagnesemia).
16.Known hypersensitivity to any palbociclib excipients.
17.Participation in an interventional trial within 30 days prior to study treatment start.
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