Breast Cancer Clinical Trial

Randomized, Open Label, Clinical Study of the Targeted Therapy, Palbociclib, to Treat Metastatic Breast Cancer

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.

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Full Description

Subjects will be randomized into one of two treatment arms following minimum of 4 and maximum of 8 cycles of induction treatment with anti-HER2 therapy. Arm A subjects will receive the experimental therapy, palbociclib, in addition to their current anti-HER2 therapy and endocrine therapy. Arm B subjects will continue to receive the anti-HER2 therapy. It is expected that the addition of palbociclib to the first-line treatment of HER2 disease will delay the onset of therapeutic resistance and ultimately prolong the survival of patients with metastatic breast cancer. The study is designed to treat the subset of patients with HER2+ disease who are also hormone receptor positive (HR+). It is also expected that palbociclib will modulate the endocrine resistance in HER2+/HR+ disease and potentiate the benefits of anti-HER2 therapy. Lastly, the current study includes a comprehensive molecular characterization of the disease at study entrance which will allow us to investigate the benefits of palbociclib in subsets of HER2+/HR+ disease such as PIK3CA mutant.

View Eligibility Criteria

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

Study is for people with:

Breast Cancer

Phase:

Phase 3

Estimated Enrollment:

496

Study ID:

NCT02947685

Recruitment Status:

Active, not recruiting

Sponsor:

Alliance Foundation Trials, LLC.

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There are 38 Locations for this study

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UCSF
San Francisco California, 94115, United States
Georgetown University Medical Center
Washington District of Columbia, 20007, United States
Baycare Healthcare (Morton Plant Mease)
Clearwater Florida, 33756, United States
Memorial Healthcare System
Hollywood Florida, 33021, United States
University of Miami
Miami Florida, 33136, United States
Florida Hospital
Orlando Florida, 32804, United States
Emory University
Atlanta Georgia, 30322, United States
University of Illinois at Chicago
Chicago Illinois, 60612, United States
The University of Chicago Medical Center
Chicago Illinois, 60637, United States
Ingalls Memorial Hospital
Harvey Illinois, 60426, United States
Cancer Center of Kansas
Wichita Kansas, 67214, United States
Ochsner Medical Center Jefferson
New Orleans Louisiana, 70121, United States
New England Cancer Specialists
Scarborough Maine, 04074, United States
Anne Arundel Medical Center
Annapolis Maryland, 21401, United States
University of Maryland - Greenebaum Comprehensive Cancer Center
Baltimore Maryland, 21201, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore Maryland, 21287, United States
Dana-Farber Cancer Institute
Boston Massachusetts, 02215, United States
Lowell General Hospital
Lowell Massachusetts, 01854, United States
Michigan Cancer Research Consortium (St. Joseph Mercy Hospital
Ann Arbor Michigan, 48106, United States
West Michigan Cancer Center
Grand Rapids Michigan, 49503, United States
Metro-Minnesota NCI Community Oncology Research Program
Minneapolis Minnesota, 55416, United States
Mayo Clinic, Rochester, MN
Rochester Minnesota, 55905, United States
Washington University School of Medicine
Saint Louis Missouri, 63110, United States
Nebraska Methodist Hospital
Omaha Nebraska, 68114, United States
University of Nebraska Medical Center
Omaha Nebraska, 68198, United States
Dartmouth Hitchcock Medical Center
Lebanon New Hampshire, 03756, United States
Hackensack Medical Center
Hackensack New Jersey, 07601, United States
The Valley Hospital, Okonite Research Center
Paramus New Jersey, 07652, United States
New Mexico Cancer Care Alliance
Albuquerque New Mexico, 87131, United States
Duke Cancer Institute
Durham North Carolina, 27710, United States
First Health of the Carolinas Cancer Center
Pinehurst North Carolina, 28374, United States
Ohio State University
Columbus Ohio, 43210, United States
Legacy Good Samaritan Hospital
Portland Oregon, 97210, United States
University of Pennsylvania
Philadelphia Pennsylvania, 19106, United States
Lexington Medical Center
West Columbia South Carolina, 29169, United States
Vanderbilt University Medical Center
Nashville Tennessee, 37204, United States
MD Anderson
Houston Texas, 77030, United States
Huntsman Cancer Institute, University of Utah
Salt Lake City Utah, 84112, United States
Monash Health
Clayton , , Australia
St. Vincent's Hospital, Sydney Kinghorn Cancer Centre
Darlinghurst , , Australia
The Canberra Hospital
Garran , , Australia
Peter MacCallum Cancer Centre, Royal Melbourne Hospital
Melbourne , , Australia
Breast Cancer Research Centre-WA
Nedlands , , Australia
Icon Cancer Care
South Brisbane , , Australia
Mater Cancer Care Centre
South Brisbane , , Australia
Calvary Mater Newcastle Hospital
Waratah , , Australia
Westmead Hospital
Westmead , , Australia
Institut de Cancérologie de l'Ouest, site Paul Papin
Angers , , France
Institut Sainte Catherine
Avignon , , France
Institut Bergonié
Bordeaux , , France
Centre Francois Baclesse
Caen , , France
Centre Hospitalier Cholet
Cholet , , France
Centre Jean Perrin
Clermont-Ferrand , , France
Centre Georges François Leclerc
Dijon , , France
CHU de Limoges
Limoges , , France
Centre Léon Bérard
Lyon , , France
Institut Paoli Calmettes
Marseille , , France
Centre Antoine Lacassagne
Nice , , France
Hôpital Saint Louis
Paris , , France
Institut Curie Site Paris
Paris , , France
Tenon Oncologie Médicale - APHP
Paris , , France
Centre CARIO-HPCA
Plerin Cedex , , France
Institut Jean Godinot
Reims , , France
Centre Henri Becquerel
Rouen , , France
Institut Curie Site Saint Cloud
Saint-Cloud , , France
Institut de Cancérologie Lucien Neuwirth
Saint-Priest-en-Jarez , , France
Centre Paul Strauss
Strasbourg , , France
Intitut Claudius Regaud
Toulouse , , France
Gustave Roussy
Villejuif , , France
Praxisklinik Krebsheilkunde für Frauen
Berlin , , Germany
Studiengesellschaft Onkologie Bielefeld
Bielefeld , , Germany
Marienhospital Bottrop
Bottrop , , Germany
Luisenkrankenhaus Düsseldorf
Düsseldorf , , Germany
Universitätsklinikum Düsseldorf, Klinik für Frauenheilkunde & Geburtshilfe
Düsseldorf , , Germany
Kliniken Essen-Mitte, Evang. Huyssens-Stiftung/Knappschaft GmbH
Essen , , Germany
Agaplesion Markus Krankenhaus
Frankfurt , , Germany
Sana-Klinikum Hameln
Hameln , , Germany
Diakovere Henriettenstift Frauenklinik
Hannover , , Germany
Vidia Christliche Kliniken Karlsruhe Vincentius-Diakonissen-Kliniken gAG Frauenklinik
Karlsruhe , , Germany
UKSH, Klinik für Gynäkologie und Geburtshilfe
Kiel , , Germany
St. Elisabeth Krankenhaus
Köln , , Germany
Praxis Prof. Nitz im Brustzentrum Niederrhein
Munster , , Germany
Universitätsklinikum Münster
Münster , , Germany
Univ. Klinikum Oldenburg AÖR Hämatologie/Onkologie
Oldenburg , , Germany
Leopoldina-Krankenhaus Schweinfurt
Schweinfurt , , Germany
HELIOS Dr. Horst Schmidt Kliniken Wiesbaden; Klinik für Gynäkologie und gynäkologische Onkologie
Wiesbaden , , Germany
Policlinico Sant'Orsola-Malpighi
Bologna , , Italy
U.O. Oncologia AOU Arcispedale Sant'Anna
Cona , , Italy
Istituto Europeo di Oncologia
Milano , , Italy
Ospedale San Raffaele
Segrate , , Italy
Ospedale Santa Maria della Misericordia
Udine , , Italy
Auckland City Hospital Cancer and Blood Research
Auckland , , New Zealand
Hospital Champalimaud
Lisboa , , Portugal
Hospital Da Luz
Lisboa , , Portugal
Hospital Beatriz Angelo
Loures , , Portugal
IPO Porto
Porto , , Portugal
Hospital Clínic de Barcelona
Barcelona , , Spain
Hospital General de Catalunya
Barcelona , , Spain
Hospital Universitari Vall d'Hebron
Barcelona , , Spain
ICO L'Hospitalet
Barcelona , , Spain
Hospital Universitario 12 de Octubre
Madrid , , Spain
Hospital Universitario de Fuenlabrada
Madrid , , Spain
Hospital Universitario Fundación Alcorcón
Madrid , , Spain
Hospital Universitario Fundación Jiménez Díaz
Madrid , , Spain
Hospital Universitario La Paz
Madrid , , Spain
Hospital Universitario Severo Ochoa
Madrid , , Spain
MD Anderson Cancer Center Spain
Madrid , , Spain
Hospital Universitario Virgen de la Arrixaca
Murcia , , Spain
Hospital Regional Universitario de Málaga
Málaga , , Spain
Complejo Hospitalario de Navarra
Navarro , , Spain
Hospital Universitario de Salamanca
Salamanca , , Spain
Complejo Hospitalario Univ. De Santiago
Santiago , , Spain
Hospital Quirón Sagrado Corazón
Seville , , Spain
Hospital Sant Joan de Reus
Tarragona , , Spain
Hospital Clínico Universitario de Valencia
Valencia , , Spain

How clear is this clinincal trial information?

Study is for people with:

Breast Cancer

Phase:

Phase 3

Estimated Enrollment:

496

Study ID:

NCT02947685

Recruitment Status:

Active, not recruiting

Sponsor:


Alliance Foundation Trials, LLC.

How clear is this clinincal trial information?

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