A Randomized, Open Label, Phase III Trial to Evaluate the Efficacy and Safety of Palbociclib + Anti-HER2 Therapy + Endocrine Therapy vs. Anti-HER2 Therapy + Endocrine Therapy After Induction Treatment for Hormone Receptor Positive (HR+)/HER2-Positive Metastatic Breast Cancer

Who is this study for? Patients with hormone receptor-positive, HER2+ metastatic breast cancer
What treatments are being studied? Palbociclib+Trastuzumab+Pertuzumab+Letrozole+Anastrozole+Exemestane+Fulvestrant
Status: Active, not recruiting
Location: See all (107) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 3
SUMMARY

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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: No
View:

• 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.

• 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

Locations
United States
California
UCSF
San Francisco
Washington, D.c.
Georgetown University Medical Center
Washington
Florida
Baycare Healthcare (Morton Plant Mease)
Clearwater
Memorial Healthcare System
Hollywood
University of Miami
Miami
Florida Hospital
Orlando
Georgia
Emory University
Atlanta
Illinois
The University of Chicago Medical Center
Chicago
University of Illinois at Chicago
Chicago
Ingalls Memorial Hospital
Harvey
Kansas
Cancer Center of Kansas
Wichita
Louisiana
Ochsner Medical Center Jefferson
New Orleans
Massachusetts
Dana-Farber Cancer Institute
Boston
Lowell General Hospital
Lowell
Maryland
Anne Arundel Medical Center
Annapolis
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore
University of Maryland - Greenebaum Comprehensive Cancer Center
Baltimore
Maine
New England Cancer Specialists
Scarborough
Michigan
Michigan Cancer Research Consortium (St. Joseph Mercy Hospital
Ann Arbor
West Michigan Cancer Center
Grand Rapids
Minnesota
Metro-Minnesota NCI Community Oncology Research Program
Minneapolis
Mayo Clinic, Rochester, MN
Rochester
Missouri
Washington University School of Medicine
Saint Louis
North Carolina
Duke Cancer Institute
Durham
First Health of the Carolinas Cancer Center
Pinehurst
Nebraska
Nebraska Methodist Hospital
Omaha
University of Nebraska Medical Center
Omaha
New Hampshire
Dartmouth Hitchcock Medical Center
Lebanon
New Jersey
Hackensack Medical Center
Hackensack
The Valley Hospital, Okonite Research Center
Paramus
New Mexico
New Mexico Cancer Care Alliance
Albuquerque
Ohio
Ohio State University
Columbus
Oregon
Legacy Good Samaritan Hospital
Portland
Pennsylvania
University of Pennsylvania
Philadelphia
South Carolina
Lexington Medical Center
West Columbia
Tennessee
Vanderbilt University Medical Center
Nashville
Texas
MD Anderson
Houston
Utah
Huntsman Cancer Institute, University of Utah
Salt Lake City
Other Locations
Australia
Monash Health
Clayton
St. Vincent's Hospital, Sydney Kinghorn Cancer Centre
Darlinghurst
The Canberra Hospital
Garran
Peter MacCallum Cancer Centre, Royal Melbourne Hospital
Melbourne
Breast Cancer Research Centre-WA
Nedlands
Icon Cancer Care
South Brisbane
Mater Cancer Care Centre
South Brisbane
Calvary Mater Newcastle Hospital
Waratah
Westmead Hospital
Westmead
France
Institut de Cancérologie de l'Ouest, site Paul Papin
Angers
Institut Sainte Catherine
Avignon
Institut Bergonié
Bordeaux
Centre Francois Baclesse
Caen
Centre Hospitalier Cholet
Cholet
Centre Jean Perrin
Clermont-ferrand
Centre Georges François Leclerc
Dijon
CHU de Limoges
Limoges
Centre Léon Bérard
Lyon
Institut Paoli Calmettes
Marseille
Centre Antoine Lacassagne
Nice
Hôpital Saint Louis
Paris
Institut Curie Site Paris
Paris
Tenon Oncologie Médicale - APHP
Paris
Centre CARIO-HPCA
Plerin Cedex
Institut Jean Godinot
Reims
Centre Henri Becquerel
Rouen
Institut Curie Site Saint Cloud
Saint-cloud
Institut de Cancérologie Lucien Neuwirth
Saint-priest-en-jarez
Centre Paul Strauss
Strasbourg
Intitut Claudius Regaud
Toulouse
Gustave Roussy
Villejuif
Germany
Praxisklinik Krebsheilkunde für Frauen
Berlin
Studiengesellschaft Onkologie Bielefeld
Bielefeld
Marienhospital Bottrop
Bottrop
Luisenkrankenhaus Düsseldorf
Düsseldorf
Universitätsklinikum Düsseldorf, Klinik für Frauenheilkunde & Geburtshilfe
Düsseldorf
Kliniken Essen-Mitte, Evang. Huyssens-Stiftung/Knappschaft GmbH
Essen
Agaplesion Markus Krankenhaus
Frankfurt
Sana-Klinikum Hameln
Hameln
Diakovere Henriettenstift Frauenklinik
Hannover
Vidia Christliche Kliniken Karlsruhe Vincentius-Diakonissen-Kliniken gAG Frauenklinik
Karlsruhe
UKSH, Klinik für Gynäkologie und Geburtshilfe
Kiel
St. Elisabeth Krankenhaus
Köln
Praxis Prof. Nitz im Brustzentrum Niederrhein
Munster
Universitätsklinikum Münster
Münster
Univ. Klinikum Oldenburg AÖR Hämatologie/Onkologie
Oldenburg
Leopoldina-Krankenhaus Schweinfurt
Schweinfurt
HELIOS Dr. Horst Schmidt Kliniken Wiesbaden; Klinik für Gynäkologie und gynäkologische Onkologie
Wiesbaden
Italy
Ospedale San Raffaele
Segrate
New Zealand
Auckland City Hospital Cancer and Blood Research
Auckland
Spain
Hospital Clínic de Barcelona
Barcelona
Hospital General de Catalunya
Barcelona
Hospital Universitari Vall d'Hebron
Barcelona
ICO L'Hospitalet
Barcelona
Hospital Universitario 12 de Octubre
Madrid
Hospital Universitario de Fuenlabrada
Madrid
Hospital Universitario Fundación Alcorcón
Madrid
Hospital Universitario Fundación Jiménez Díaz
Madrid
Hospital Universitario La Paz
Madrid
Hospital Universitario Severo Ochoa
Madrid
MD Anderson Cancer Center Spain
Madrid
Hospital Regional Universitario de Málaga
Málaga
Hospital Universitario Virgen de la Arrixaca
Murcia
Complejo Hospitalario de Navarra
Navarro
Hospital Universitario de Salamanca
Salamanca
Complejo Hospitalario Univ. De Santiago
Santiago
Hospital Quirón Sagrado Corazón
Seville
Hospital Sant Joan de Reus
Tarragona
Hospital Clínico Universitario de Valencia
Valencia
Time Frame
Start Date: June 21, 2017
Estimated Completion Date: March 31, 2026
Participants
Target number of participants: 496
Treatments
Experimental: Arm A
Palbociclib 125 mg daily + AntiHER2 Therapy (trastuzumab/pertuzumab) q3wks + Endocrine Therapy (letrozole, anastrozole, exemstane OR fulvestratnt) until confirmed disease progression
Active Comparator: Arm B
AntiHER2 Therapy (trastuzumab/pertuzumab) q3wks + Endocrine Therapy (letrozole, anastrozole, exemstane OR fulvestrant) until confirmed disease progression
Authors
Jean-Philippe Jaquin, Miguel Q Fandino, Christoph Mundenke, Nicole Gorddard, Katherine Tzaczuk, Alfonso S Muñoz, César A Sánchez, Aleix P Aparicio, Adam Brufsky, Charles Kuzma, Jane Meisel, Jose Eugenio Najera, Rima Couzi, Robert Behrens, John Cole, Elgene Lim, Donald Northfelt, Regan Look, Michael Maroules, Kimberly Kruczek, Daniel Flora, Kathleen Harnden, Michael Schwartz, Elizabeth Prystas, Ingrid Mayer, Kirsten Leu, Sarah Sinclair, Ben Yan, Gary Schwartz, Elie Dib, Brian Heller, Peter Kaufman, Eleonora Teplinsky, Kent Hoskins, Carlos Alemany, Paula Pohlmann, Pavankumar Tandra, Steven Madden, Matthew Goetz, Norah Lynn Henry, Rashmi Murthy, Kathy Albain, Carmen Calfa, Rachel Lerner, Lavanya Sundararajan, Richard Zuniga, Rafael V Vazquez, Rajesh Bajaj, Olwen Hahn, Shaker Dakhil, Vered Stearns, Chiara Battelli, Michel Velez, Haeseong Park, Nasfat Shehadeh, Otto Metzger, Deena Graham, Aurelio Castrellon, Angela DeMichele, Carol Tweed, Alain Zannetti, Barbara Pistilli, Joseph Gligorov, Paule Augereau, Christelle Jouannaud, Tanja Fehm, Peter Klare, Kristina Lubbe, Claudia Schumacher, Florian Clatot, Pierre Heudel, Thomas Noesselt, Mattea Reinisch, Francesco Ricci, Richard de Boer, Joke Tio, Oliver Tome, Florence Dalenc, Christelle Levy, Claus-Henning Köhne, Luis Teixeira, Renaud Sabatier, Raquel von Schumann, Thierry Petit, Nathalie Quenel-Tueux, Hans-Christian Kolberg, Michael Weigel, Philippe Follana, Marc Thill, Audrey Hennequin, Marianne Just, Pilar Sánchez Henarejos, Cinta Albacar, David Porter, Raúl M Vázquez, Maren Darsow, Kelly Westbrook, Xavier G Farré, Sagar Sardesai, Nicole McCarthy, Luca Gianni, Arlene Chan, Julien Grenier, Anne-Claire Hardy-Bessard, Ali Conlin, Shylenda Sreenivasappa, Begoña Bermejo, Kathleen Yost, Nguyet Le-Lindqwister, Nicholas Wilcken, Ursa Brown-Glaberman, Michael Eichbaum, Susana Sánchez, Eva Ciruelos, Marie Ange Mouret Reynier, Michelle White, Yann I Peron, Diana Moreno, Juan Antonio Virizuela, Rafael López, Jose E González, Janine Lombard, Amy Jo Chien, Laurence Venat Bouvet, Natasha Woodward, Santiago Escrivà, Katherine Tkaczuk
Related Therapeutic Areas
Sponsors
Collaborators: Pfizer, Breast Cancer Trials, Australia and New Zealand, PrECOG, LLC., SOLTI Breast Cancer Research Group, German Breast Group, Syneos Health, Fondazione Michelangelo, UNICANCER
Leads: Alliance Foundation Trials, LLC.

This content was sourced from clinicaltrials.gov

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