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

January 29, 2024 updated by: Alliance Foundation Trials, LLC.

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Estimated)

496

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria (Preliminary Screening)

  1. Signed Preliminary Screening Informed Consent Form obtained prior to any study specific assessments and procedures
  2. Age ≥18 years (or per national guidelines)
  3. 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.
  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. 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.

  6. 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)

  7. Signed Main Informed Consent Form 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 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).
  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) 12 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

    Prior Treatment Specifics

  14. 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.
  15. 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).

  16. 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

  17. Absolute neutrophil count ≥ 1,000/mm3
  18. Platelets ≥ 100,000/mm3
  19. Hemoglobin ≥ 10g/dL
  20. Total serum bilirubin ≤ ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin within normal range in patients with documented Gilbert's Syndrome.
  21. Aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) ≤ 3 × institutional ULN (≤5 x ULN if liver metastases are present).
  22. 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.
  23. Left ventricular ejection fraction (LVEF) ≥ 50% at baseline as determined by either ECHO or MUGA

Exclusion Criteria (Randomization)

  1. Concurrent therapy with other Investigational Products.
  2. Prior therapy with any CDK 4/6 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 (see Section 8.6.3 for list of strong inhibitors or inducers of CYP3A isoenzymes).
  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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A
Palbociclib 125 mg daily + AntiHER2 Therapy (trastuzumab/pertuzumab) q3wks + Endocrine Therapy (letrozole, anastrozole, exemstane OR fulvestratnt) until confirmed disease progression
Drug: palbociclib
o Starting dose: 125 mg capsule taken orally once per day for 21 days followed by 7 days off to complete 28 day cycle. Dose reductions: 100 mg, 75 mg. allowed. Number of Cycles: until progression or unacceptable toxicity develops
Other Names:
  • Ibrance
Drug: trastuzumab
Patients must have received a minimum of 4 and maximum of 8 cycles of induction therapy prior to randomization to Arm A or B, at which point they will continue on antiHER2 therapy and endocrine therapy, with or without palbociclib. Trastuzumab dosing will be determined based on a loading dose of 8mg trastuzumab/kg body weight for Q3WK dosing schedules or a maintenance dose of 6mg/kg trastuzumab/kg dosing weight for Q3WK dosing schedules. Loading dose will be administered on Cycle 1, Day 1.
Other Names:
  • Herceptin
Drug: pertuzumab
Patients must have received a minimum of 4 and maximum of 8 cycles of induction therapy prior to randomization to Arm A or B, at which point they will continue on antiHER2 therapy and endocrine therapy, with or without palbociclib.Pertuzumab will be administered at a loading dose of 840 mg infusion and then at a maintenance dose of 420 mg q3wks. If patient is within 5 weeks of receiving loading dose at Cycle 1, Day 1, patient may start with maintenance dose of 420 mg.
Other Names:
  • Perjeta
Drug: letrozole
There are several allowed endocrine treatment agents for Arm A and Arm B of this study. Administration is performed on an outpatient, self-administration basis according to local requirements and local standard practice. Endocrine treatment may have started before the patient enters the study. Agents will be administered at the discretion of principal investigator as well as according to standard institutional or regional practice. Recommended dosing regimen for letrozole oral therapy is 2.5 mg orally, once a day.
Other Names:
  • Femara
Drug: Anastrozole
There are several allowed endocrine treatment agents for Arm A and Arm B of this study. Administration is performed on an outpatient, self-administration basis according to local requirements and local standard practice. Endocrine treatment may have started before the patient enters the study. Agents will be administered at the discretion of principal investigator as well as according to standard institutional or regional practice. Recommended dosing regimen for anastrozole is 1 mg orally, once a day.
Other Names:
  • Arimidex
Drug: Exemestane
There are several allowed endocrine treatment agents for Arm A and Arm B of this study. Administration is performed on an outpatient, self-administration basis according to local requirements and local standard practice. Endocrine treatment may have started before the patient enters the study. Agents will be administered at the discretion of principal investigator as well as according to standard institutional or regional practice. Recommended dosing regimen for exemestane is 25 mg orally, once a day.
Other Names:
  • Aromasin
Drug: Fulvestrant
There are several allowed endocrine treatment agents for Arm A and Arm B of this study. Administration is performed on an outpatient, self-administration basis according to local requirements and local standard practice. Endocrine treatment may have started before the patient enters the study. Agents will be administered at the discretion of principal investigator as well as according to standard institutional or regional practice. Recommended dosing regimen for Fulvestrant is 250 mg injections on Day 1 and Day 15 of Cycle 1, and q4weeks thereafter.
Other Names:
  • Faslodex
Active Comparator: Arm B
AntiHER2 Therapy (trastuzumab/pertuzumab) q3wks + Endocrine Therapy (letrozole, anastrozole, exemstane OR fulvestrant) until confirmed disease progression
Drug: pertuzumab
Patients must have received a minimum of 4 and maximum of 8 cycles of induction therapy prior to randomization to Arm A or B, at which point they will continue on antiHER2 therapy and endocrine therapy, with or without palbociclib.Pertuzumab will be administered at a loading dose of 840 mg infusion and then at a maintenance dose of 420 mg q3wks. If patient is within 5 weeks of receiving loading dose at Cycle 1, Day 1, patient may start with maintenance dose of 420 mg.
Other Names:
  • Perjeta
Drug: letrozole
There are several allowed endocrine treatment agents for Arm A and Arm B of this study. Administration is performed on an outpatient, self-administration basis according to local requirements and local standard practice. Endocrine treatment may have started before the patient enters the study. Agents will be administered at the discretion of principal investigator as well as according to standard institutional or regional practice. Recommended dosing regimen for letrozole oral therapy is 2.5 mg orally, once a day.
Other Names:
  • Femara
Drug: Anastrozole
There are several allowed endocrine treatment agents for Arm A and Arm B of this study. Administration is performed on an outpatient, self-administration basis according to local requirements and local standard practice. Endocrine treatment may have started before the patient enters the study. Agents will be administered at the discretion of principal investigator as well as according to standard institutional or regional practice. Recommended dosing regimen for anastrozole is 1 mg orally, once a day.
Other Names:
  • Arimidex
Drug: Exemestane
There are several allowed endocrine treatment agents for Arm A and Arm B of this study. Administration is performed on an outpatient, self-administration basis according to local requirements and local standard practice. Endocrine treatment may have started before the patient enters the study. Agents will be administered at the discretion of principal investigator as well as according to standard institutional or regional practice. Recommended dosing regimen for exemestane is 25 mg orally, once a day.
Other Names:
  • Aromasin
Drug: Fulvestrant
There are several allowed endocrine treatment agents for Arm A and Arm B of this study. Administration is performed on an outpatient, self-administration basis according to local requirements and local standard practice. Endocrine treatment may have started before the patient enters the study. Agents will be administered at the discretion of principal investigator as well as according to standard institutional or regional practice. Recommended dosing regimen for Fulvestrant is 250 mg injections on Day 1 and Day 15 of Cycle 1, and q4weeks thereafter.
Other Names:
  • Faslodex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Progression-free survival (PFS) as assessed by Investigator
Time Frame: 24 months
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: 24 months
Defined as time from date of randomization to date of death due to any cause
24 months
3 and 5 year survival probabilities
Time Frame: 24 months
Survival probabilities will be estimated using the Kaplan-Meier method
24 months
Duration of Response (DOR)
Time Frame: 24 months
Defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression or to death from any cause, whichever occurs first
24 months
Clinical Benefit Rate (CBR: CR or PR or SD ≥ 24 weeks
Time Frame: 24 months
The Clinical Benefit Rate (CBR) on each treatment arm will be estimated by dividing the number of patients with CR, PR, or SD/Non-CR and Non-PD (for patients with measurable disease) ≥ 24 weeks by the number of patients randomized to the treatment arm.
24 months
Safety: Type incidence and severity (as graded by NCI CTCAE v 4.0)
Time Frame: 24 months
Seriousness and attribution to the study medications of AEs and any laboratory abnormalities
24 months
Patient Reported Outcomes
Time Frame: 24 months
Time to symptom progression (FACT-B PFB-TOI), breast cancer specific health treatment related quality of life and general health status
24 months
Objective Response Rate (OR: CR or PR)
Time Frame: 24 months
Defined as complete response (CR) or partial response (PR) according to RECIST v1.1
24 months
Incidence of CNS Metastasis
Time Frame: 24 months
Compare the incidence of CNS metastasis between treatment arms
24 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Trough Plasma concentration of palbociclib, trastuzumab and pertuzumab
Time Frame: Palbociclib PK assessment: Day 22, Cycle 1, No; Pertuzumab, Trastuzumab PK assessment: Day 1, Cycle 4
only for patients enrolled in the US
Palbociclib PK assessment: Day 22, Cycle 1, No; Pertuzumab, Trastuzumab PK assessment: Day 1, Cycle 4
PIK3CA genotype assessed in circulating cfDNA
Time Frame: Day 1, Cycle 1, Day 1, Cycle 4, End of Treatment, approx 24 months
Progression Free Survival (PFS) based upon investigator assessment of progression between patients in the two treatment arms in the subset of patients with tumors bearing a PIK3CA mutation.
Day 1, Cycle 1, Day 1, Cycle 4, End of Treatment, approx 24 months
Tumor tissue biomarkers including genes, proteins, and RNA expression
Time Frame: Baseline
Will evaluate baseline tumor and blood-based markers as predictors of benefit from the addition of palbociclib to anti-HER2 therapy plus endocrine therapy
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alliance Foundation Trials, LLC.

Collaborators

Pfizer
Syneos Health
UNICANCER
German Breast Group
SOLTI Breast Cancer Research Group
PrECOG, LLC.
Fondazione Michelangelo
Breast Cancer Trials, Australia and New Zealand

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 21, 2017

Primary Completion (Estimated)

April 30, 2024

Study Completion (Estimated)

July 31, 2026

Study Registration Dates

First Submitted

October 26, 2016

First Submitted That Met QC Criteria

October 26, 2016

First Posted (Estimated)

October 28, 2016

Study Record Updates

Last Update Posted (Actual)

January 30, 2024

Last Update Submitted That Met QC Criteria

January 29, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AFT-38

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on HER-2 Positive Breast Cancer

Clinical Trials on palbociclib

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Burundi

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe