Randomized, Open Label, Clinical Study of the Targeted Therapy, Palbociclib, to Treat Metastatic Breast Cancer (PATINA)
HER-2 Positive Breast Cancer, Estrogen Receptor Positive Breast Cancer
About this trial
This is an interventional treatment trial for HER-2 Positive Breast Cancer focused on measuring breast cancer, malignant tumor of the breast, HER2+, HR+, metastatic breast cancer
Eligibility Criteria
Inclusion Criteria (Preliminary Screening)
- Signed Preliminary Screening Informed Consent Form obtained prior to any study specific assessments and procedures
- Age ≥18 years (or per national guidelines)
- Patients 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.
- Patients must agree to provide 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.
Patients 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 Screening)
- Signed Main Informed Consent Form 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 which is 6 months after the last treatment with palbociclib if they are in Arm A and for 7 months after last treatment with trastuzumab if in either Arm A or Arm B 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) 12 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
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 can randomize immediately following completion of their induction therapy, or for those who have already completed induction, a gap of 12 weeks between their last infusion/dose of induction therapy and the C1D1 visit is permitted. Patients are eligible provided they are without evidence of disease progression by local assessment (i.e. CR, PR or SD).
Patients with a history or presence of asymptomatic 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 induction 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) ≤ 3 × institutional ULN (≤5 x ULN if liver metastases are present).
- Serum creatinine below the upper limit of normal (ULN) of the institutional normal range 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 as determined by either ECHO or MUGA
Exclusion Criteria (Randomization)
- Concurrent therapy with other Investigational Products.
- Prior therapy with any CDK 4/6 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 (see Section 8.6.3 for list of strong inhibitors or inducers of CYP3A isoenzymes).
- 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 >480 msec, 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
Sites / Locations
- UCSF
- Georgetown University Medical Center
- Baycare Healthcare (Morton Plant Mease)
- Memorial Healthcare System
- University of Miami
- Florida Hospital
- Emory University
- University of Illinois at Chicago
- The University of Chicago Medical Center
- Ingalls Memorial Hospital
- Cancer Center of Kansas
- Ochsner Medical Center Jefferson
- New England Cancer Specialists
- Anne Arundel Medical Center
- University of Maryland - Greenebaum Comprehensive Cancer Center
- Johns Hopkins University/Sidney Kimmel Cancer Center
- Dana-Farber Cancer Institute
- Lowell General Hospital
- Michigan Cancer Research Consortium (St. Joseph Mercy Hospital
- West Michigan Cancer Center
- Metro-Minnesota NCI Community Oncology Research Program
- Mayo Clinic, Rochester, MN
- Washington University School of Medicine
- Nebraska Methodist Hospital
- University of Nebraska Medical Center
- Dartmouth Hitchcock Medical Center
- Hackensack Medical Center
- The Valley Hospital, Okonite Research Center
- New Mexico Cancer Care Alliance
- Duke Cancer Institute
- First Health of the Carolinas Cancer Center
- Ohio State University
- Legacy Good Samaritan Hospital
- University of Pennsylvania
- Lexington Medical Center
- Vanderbilt University Medical Center
- MD Anderson
- Huntsman Cancer Institute, University of Utah
- Monash Health
- St. Vincent's Hospital, Sydney Kinghorn Cancer Centre
- The Canberra Hospital
- Peter MacCallum Cancer Centre, Royal Melbourne Hospital
- Breast Cancer Research Centre-WA
- Icon Cancer Care
- Mater Cancer Care Centre
- Calvary Mater Newcastle Hospital
- Westmead Hospital
- Institut de Cancérologie de l'Ouest, site Paul Papin
- Institut Sainte Catherine
- Institut Bergonié
- Centre Francois Baclesse
- Centre Hospitalier Cholet
- Centre Jean Perrin
- Centre Georges François Leclerc
- CHU de Limoges
- Centre Léon Bérard
- Institut Paoli Calmettes
- Centre Antoine Lacassagne
- Hôpital Saint Louis
- Institut Curie Site Paris
- Tenon Oncologie Médicale - APHP
- Centre CARIO-HPCA
- Institut Jean Godinot
- Centre Henri Becquerel
- Institut Curie Site Saint Cloud
- Institut de Cancérologie Lucien Neuwirth
- Centre Paul Strauss
- Intitut Claudius Regaud
- Gustave Roussy
- Praxisklinik Krebsheilkunde für Frauen
- Studiengesellschaft Onkologie Bielefeld
- Marienhospital Bottrop
- Luisenkrankenhaus Düsseldorf
- Universitätsklinikum Düsseldorf, Klinik für Frauenheilkunde & Geburtshilfe
- Kliniken Essen-Mitte, Evang. Huyssens-Stiftung/Knappschaft GmbH
- Agaplesion Markus Krankenhaus
- Sana-Klinikum Hameln
- Diakovere Henriettenstift Frauenklinik
- Vidia Christliche Kliniken Karlsruhe Vincentius-Diakonissen-Kliniken gAG Frauenklinik
- UKSH, Klinik für Gynäkologie und Geburtshilfe
- St. Elisabeth Krankenhaus
- Praxis Prof. Nitz im Brustzentrum Niederrhein
- Universitätsklinikum Münster
- Univ. Klinikum Oldenburg AÖR Hämatologie/Onkologie
- Leopoldina-Krankenhaus Schweinfurt
- HELIOS Dr. Horst Schmidt Kliniken Wiesbaden; Klinik für Gynäkologie und gynäkologische Onkologie
- Policlinico Sant'Orsola-Malpighi
- U.O. Oncologia AOU Arcispedale Sant'Anna
- Istituto Europeo di Oncologia
- Ospedale San Raffaele
- Ospedale Santa Maria della Misericordia
- Auckland City Hospital Cancer and Blood Research
- Hospital Champalimaud
- Hospital Da Luz
- Hospital Beatriz Angelo
- IPO Porto
- Hospital Clínic de Barcelona
- Hospital General de Catalunya
- Hospital Universitari Vall d'Hebron
- ICO L'Hospitalet
- Hospital Universitario 12 de Octubre
- Hospital Universitario de Fuenlabrada
- Hospital Universitario Fundación Alcorcón
- Hospital Universitario Fundación Jiménez Díaz
- Hospital Universitario La Paz
- Hospital Universitario Severo Ochoa
- MD Anderson Cancer Center Spain
- Hospital Universitario Virgen de la Arrixaca
- Hospital Regional Universitario de Málaga
- Complejo Hospitalario de Navarra
- Hospital Universitario de Salamanca
- Complejo Hospitalario Univ. De Santiago
- Hospital Quirón Sagrado Corazón
- Hospital Sant Joan de Reus
- Hospital Clínico Universitario de Valencia
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Arm A
Arm B
Palbociclib 125 mg daily + AntiHER2 Therapy (trastuzumab/pertuzumab) q3wks + Endocrine Therapy (letrozole, anastrozole, exemstane OR fulvestratnt) until confirmed disease progression
AntiHER2 Therapy (trastuzumab/pertuzumab) q3wks + Endocrine Therapy (letrozole, anastrozole, exemstane OR fulvestrant) until confirmed disease progression