HR+/HER2+ metastatic breast cancer MedDRA version: 23.0 Level: PT Classification code 10065430 Term: HER2 positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 27.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 23.0 Level: LLT Classification code 10070575 Term: Estrogen re
Conditions
Interventions
Trade Name: IBRANCE 125mg
Product Name: IBRANCE
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: PALBOCICLIB
CAS Number: 571190-30-2
Concentration unit: mg milligram(s)
Concentration type: equa
Sponsors
Alliance Foundation Trials, LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria Screening 1. Signed informed consent obtained prior to any study specific assessments and procedures 2. Age =18 years (or per national guidelines) 3. Participants must have histologically confirmed invasive breast cancer that is metastatic or not amenable for resection or radiation therapy with curative intent. Histological documentation of metastatic/recurrent breast cancer is not required if there is unequivocal evidence for recurrence of the breast cancer. 4. Patients must have histologically confirmed HER2+ and hormone receptor positive (ER+ and/or PR+), metastatic breast cancer. ER, PR and HER2 measurements should be performed according to institutional guidelines, in a CLIA-approved setting in the US or certified laboratories for Non-US regions. Cut-off values for positive/negative staining should be in accordance with current ASCO/CAP (American Society of Clinical Oncology/College of American Pathologists) guidelines. 5. Sites must be able to submit a representative formalin-fixed paraffin-embedded (FFPE) tumor tissue block (preferred) from primary breast or metastatic site (archival) OR at least 15 freshly cut unstained slides from such a block, along with a pathology report documenting HER2 positivity and hormone receptor positivity. 6. Sites should be willing to provide a representative tumor specimen obtained from recently biopsied metastatic disease if clinically feasible. This is recommended but optional tissue Inclusion Criteria (Randomization) 7. Signed informed consent obtained prior to any study specific assessments and procedures 8. Age = 18 years (or per national guidelines) 9. ECOG performance status 0-1 10. Patients must be able and willing to swallow and retain oral medication without a condition that would interfere with enteric absorption. 11. Serum or urine pregnancy test must be negative within 7 days of randomization in women of childbearing potential. Pregnancy testing does not need to be pursued in patients who are judged as postmenopausal before randomization, as determined by local practice, or who have undergone bilateral oophorectomy, total hysterectomy, or bilateral tubal ligation. Women of childbearing potential and male patients randomized into the study must use adequate contraception for the duration of protocol treatment and for 6 months after the last treatment with palbociclib if they are in Arm A. Adequate contraception is defined as one highly effective form (i.e. abstinence, (fe)male sterilization OR two effective forms (e.g. non-hormonal IUD and condom / occlusive cap with spermicidal foam / gel / film / cream / suppository). 12. Resolution of all acute toxic effects of prior induction anti-HER2-based chemotherapy regimen to NCI CTCAE version 4.0 Grade =1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion) 3-6 weeks between last dose of chemotherapy–anti-HER2therapy and randomization are allowed. Endocrine therapy could start before study randomization. 13. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures 14. Evidence of (a) personally signed and dated informed consent document indicating that the patient (or a legal representative) has been informed of all pertinent aspects of the study before any study specific activity is performed Inclusion Criteria 15-24: Please see full protocol Are the trial subjects under 18? no Numb
Exclusion criteria
Exclusion criteria: 1. Concurrent therapy with other Investigational Products. 2. Prior therapy with any CDK inhibitor. 3. History of allergic reactions attributed to compounds of chemical or biologic composition similar to palbociclib. 4. Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A isoenzymes within 7 days of randomization. 5. Uncontrolled current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, diabetes, or psychiatric illness/social situations that would limit compliance with study requirements. Ability to comply with study requirements is to be assessed by each investigator at the time of screening for study participation. 6. Pregnant women, or women of childbearing potential without a negative pregnancy test (serum or urine) within 7 days prior to randomization, irrespective of the method of contraception used, are excluded from this study because the effect of palbociclib on a developing fetus is unknown. Breastfeeding must be discontinued prior to study entry. 7. Patients on combination antiretroviral therapy, i.e. those who are HIV-positive, are ineligible because of the potential for pharmacokinetic interactions or increased immunosuppression with palbociclib. 8. QTc interval >480 msec, Brugada syndrome or known history of QTc prolongation or Torsade de Pointes. 9. Patients with clinically significant history of liver disease, including viral or other known hepatitis, current alcohol abuse, or cirrhosis
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Overall Survival (OS) 2. 3-year and 5-year survival probabilities 3. Objective response (OR: CR or PR) 4. Duration of response (DOR) 5. Clinical Benefit Rate (CBR: CR or PR or SD = 24 weeks) 6. Incidence of CNS metastasis 7. Safety: Type, incidence, severity (as graded by the NCI CTCAE v. 4.0), seriousness and attribution to the study medications of AEs and any laboratory abnormalities 8. Patient Reported Outcomes: Time to symptom progression (FACT-B PFB-TOI), breast cancer specific health treatment related quality of life and general health status ;Timepoint(s) of evaluation of this end point: All secondary endpoints, will be assessed at the same timepoints as the Primary Criterion. | — |
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to demonstrate that the combination of palbociclib with anti-HER2 therapy plus endocrine therapy is superior to anti-HER2-based therapy plus endocrine therapy in prolonging PFS in participants with hormone receptor-positive, HER2+ metastatic breast cancer who have not received any prior treatment beyond induction treatment in this setting.;Secondary Objective: 1. To compare measures of tumor control (including PFS, OR, CBR, DOR) between the treatment arms 2. To compare median overall survival and overall survival probabilities at 3-years and 5-years between the treatment groups 3. To compare safety and tolerability between the treatment arms 4. To compare the incidence of CNS metastasis between the treatment arms 5. To compare patient reported time to symptom progression as assessed by the FACT-B TOI-PFB 6. To compare patient reported breast cancer specific health related quality of life (HRQOL) and general health status. ;Primary end point(s): Progression-free survival (PFS) as assessed by the Investigator;Timepoint(s) of evaluation of this end point: Based on the expected recruitment and treatment duration, the primary endpoint analysis is expected to take place 18 month after randomization of the last Patient. | — |
Countries
Australia, France, Germany, Italy, New Zealand, Portugal, Spain, United States
Contacts
Public ContactSenior Project Manager
Alliance Foundation Trials, LLC
Outcome results
None listed