Randomized, Open Label, Clinical Study of the Targeted Therapy, Palbociclib, to Treat Metastatic Breast Cancer
Describes the nature of a clinical study. Types include:
- Observational study — observes people and measures outcomes without affecting results.
- Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
- Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.
- Scottsdale/Phoenix, Arizona: 17-002444
- Rochester, Minnesota: 17-002444
NCT ID: NCT02947685
Sponsor Protocol Number: AFT-38
About this study
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 alone in improving the outcomes of subjects with hormone receptor-positive, HER2+ metastatic breast cancer.
Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.See eligibility criteria
Inclusion Criteria (Screening)
- Signed informed consent obtained prior to any study specific assessments and procedures
- Age ≥18 years (or per national guidelines)
- 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.
- 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.
- Representative formalin-fixed paraffin-embedded (FFPE) tumor tissue block (preferred) or at least 15 unstained slides along with a pathology report documenting HER2 positivity and hormone receptor positivity
- Representative tumor specimen obtained from metastatic disease if clinically feasible. This could include tumor obtained from metastatic biopsies performed for diagnostic purpose or biopsies performed as part of the current study.
Inclusion Criteria (Randomization)
- Signed informed consent obtained prior to any study specific assessments and procedures
- Age ≥ 18 years (or per national guidelines)
- ECOG performance status 0-1
- Patients must be able and willing to swallow and retain oral medication without a condition that would interfere with enteric absorption.
- 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).
- 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.
- Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
- 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 Prior Treatment Specifics
- Patients may or may not have received neo/adjuvant therapy, but must have a disease-free interval from completion of anti-HER2 therapy to metastatic diagnosis ≥6 months.
- Patients must have received an acceptable, standard, chemotherapy containing anti-HER2 based induction therapy for the treatment of metastatic breast cancer prior to study enrollment. For this study, chemotherapy is limited to a taxane or vinorelbine (only for trastuzumab-based regimen). Eligible patients are expected to have completed 6 cycles of chemotherapy containing anti-HER2-therapy treatment. A minimum of 4 cycles of treatment is acceptable for patients experiencing significant toxicity associated with treatment as long as they are without evidence of disease progression (i.e. CR, PR or SD). The maximum number of cycles is 8. Patients are eligible provided they are without evidence of disease progression by local assessment (i.e. CR, PR or SD).
- Participants with a history of treated CNS metastases are eligible, provided they meet all of the following criteria:
- Disease outside the CNS is present.
- No evidence of interim progression between the completion of CNS directed therapy and the screening radiographic study
- No history of intracranial hemorrhage or spinal cord hemorrhage
- Not requiring anti-convulsants for symptomatic control
- Minimum of 3 weeks between completion of CNS radiotherapy and Cycle 1 Day 1 and recovery from significant (Grade ≥ 3) acute toxicity with no ongoing requirement for corticosteroid Baseline Body Function Specifics
- Absolute neutrophil count ≥ 1,000/mm3
- Platelets ≥ 100,000/mm3
- Hemoglobin ≥ 10g/dL
- Total serum bilirubin ≤ ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin within normal range in patients with documented Gilbert's Syndrome.
- Aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) ≤ 1.5 × institutional ULN.
- Serum creatinine within normal institutional limits or creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with serum creatinine levels above institutional ULN.
- Left ventricular ejection fraction (LVEF)≥ 50% at baseline (within 42 days of randomization) as determined by either ECHO or MUGA
Exclusion Criteria (Randomization)
- Concurrent therapy with other Investigational Products.
- Prior therapy with any CDK inhibitor.
- History of allergic reactions attributed to compounds of chemical or biologic composition similar to palbociclib.
- Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A isoenzymes within 7 days of randomization.
- 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.
- 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.
- 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.
- QTc interval >480msec, Brugada syndrome or known history of QTc prolongation or Torsade de Pointes.
- Patients with clinically significant history of liver disease, including viral or other known hepatitis, current alcohol abuse, or cirrhosis
Participating Mayo Clinic locations
Study statuses change often. Please contact us for help.