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

• ClinicalTrials.gov Identifier: NCT02947685
• Recruitment Status: Active, not recruiting
• First Posted: October 28, 2016
• Last Update Posted: May 30, 2023
• Sponsor: Alliance Foundation Trials, LLC.
• Collaborators: Pfizer; German Breast Group; Fondazione Michelangelo; PrECOG, LLC.; Breast Cancer Trials, Australia and New Zealand; Syneos Health; SOLTI Breast Cancer Research Group; UNICANCER
• Information provided by (Responsible Party): Alliance Foundation Trials, LLC.

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
HER-2 Positive Breast Cancer; Estrogen Receptor Positive Breast Cancer	Drug: palbociclib; Drug: trastuzumab; Drug: pertuzumab; Drug: letrozole; Drug: Anastrozole; Drug: Exemestane; Drug: Fulvestrant	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 496 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: June 21, 2017
• Estimated Primary Completion Date: December 30, 2023
• Estimated Study Completion Date: July 31, 2026

Arms and Interventions

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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Faslodex

Outcome Measures

Primary Outcome Measures :

1. Progression-free survival (PFS) as assessed by Investigator [ Time Frame: 24 months ]

Secondary Outcome Measures :

1. Overall Survival (OS) [ Time Frame: 24 months ]
   Defined as time from date of randomization to date of death due to any cause
2. 3 and 5 year survival probabilities [ Time Frame: 24 months ]
   Survival probabilities will be estimated using the Kaplan-Meier method
3. 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
4. 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
5. 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.
6. 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
7. 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
8. Incidence of CNS Metastasis [ Time Frame: 24 months ]
   Compare the incidence of CNS metastasis between treatment arms

Other Outcome Measures:

1. 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
2. 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.
3. 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

UCSF

San Francisco, California, United States, 94115

United States, District of Columbia

Georgetown University Medical Center

Washington, District of Columbia, United States, 20007

United States, Florida

Baycare Healthcare (Morton Plant Mease)

Clearwater, Florida, United States, 33756

Memorial Healthcare System

Hollywood, Florida, United States, 33021

University of Miami

Miami, Florida, United States, 33136

Florida Hospital

Orlando, Florida, United States, 32804

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30322

United States, Illinois

University of Illinois at Chicago

Chicago, Illinois, United States, 60612

The University of Chicago Medical Center

Chicago, Illinois, United States, 60637

Ingalls Memorial Hospital

Harvey, Illinois, United States, 60426

United States, Kansas

Cancer Center of Kansas

Wichita, Kansas, United States, 67214

United States, Louisiana

Ochsner Medical Center Jefferson

New Orleans, Louisiana, United States, 70121

United States, Maine

New England Cancer Specialists

Scarborough, Maine, United States, 04074

United States, Maryland

Anne Arundel Medical Center

Annapolis, Maryland, United States, 21401

University of Maryland - Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, United States, 21201

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States, 21287

United States, Massachusetts

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02215

Lowell General Hospital

Lowell, Massachusetts, United States, 01854

United States, Michigan

Michigan Cancer Research Consortium (St. Joseph Mercy Hospital

Ann Arbor, Michigan, United States, 48106

West Michigan Cancer Center

Grand Rapids, Michigan, United States, 49503

United States, Minnesota

Metro-Minnesota NCI Community Oncology Research Program

Minneapolis, Minnesota, United States, 55416

Mayo Clinic, Rochester, MN

Rochester, Minnesota, United States, 55905

United States, Missouri

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

United States, Nebraska

Nebraska Methodist Hospital

Omaha, Nebraska, United States, 68114

University of Nebraska Medical Center

Omaha, Nebraska, United States, 68198

United States, New Hampshire

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States, 03756

United States, New Jersey

Hackensack Medical Center

Hackensack, New Jersey, United States, 07601

The Valley Hospital, Okonite Research Center

Paramus, New Jersey, United States, 07652

United States, New Mexico

New Mexico Cancer Care Alliance

Albuquerque, New Mexico, United States, 87131

United States, North Carolina

Duke Cancer Institute

Durham, North Carolina, United States, 27710

First Health of the Carolinas Cancer Center

Pinehurst, North Carolina, United States, 28374

United States, Ohio

Ohio State University

Columbus, Ohio, United States, 43210

United States, Oregon

Legacy Good Samaritan Hospital

Portland, Oregon, United States, 97210

United States, Pennsylvania

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19106

United States, South Carolina

Lexington Medical Center

West Columbia, South Carolina, United States, 29169

United States, Tennessee

Vanderbilt University Medical Center

Nashville, Tennessee, United States, 37204

United States, Texas

MD Anderson

Houston, Texas, United States, 77030

United States, Utah

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, United States, 84112

Australia

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

France

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

Germany

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

Italy

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

New Zealand

Auckland City Hospital Cancer and Blood Research

Auckland, New Zealand

Portugal

Hospital Champalimaud

Lisboa, Portugal

Hospital Da Luz

Lisboa, Portugal

Hospital Beatriz Angelo

Loures, Portugal

IPO Porto

Porto, Portugal

Spain

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

Sponsors and Collaborators

Alliance Foundation Trials, LLC.

Pfizer

German Breast Group

Fondazione Michelangelo

PrECOG, LLC.

Breast Cancer Trials, Australia and New Zealand

Syneos Health

SOLTI Breast Cancer Research Group

UNICANCER

More Information

Publications of Results:

Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, Ettl J, Patel R, Pinter T, Schmidt M, Shparyk Y, Thummala AR, Voytko NL, Fowst C, Huang X, Kim ST, Randolph S, Slamon DJ. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015 Jan;16(1):25-35. doi: 10.1016/S1470-2045(14)71159-3. Epub 2014 Dec 16.

Finn, R.S., et al., PALOMA-2: Primary results from a phase III trial of palbociclib (P) with letrozole (L) compared with letrozole alone in postmenopausal women with ER+/HER2- advanced breast cancer (ABC). ASCO Meeting Abstracts, 2016. 34(15_suppl): p. 507.

Paridaens R, Dirix L, Lohrisch C, Beex L, Nooij M, Cameron D, Biganzoli L, Cufer T, Duchateau L, Hamilton A, Lobelle JP, Piccart M; European Organization for the Research and Treatment of Cancer (EORTC)- Investigational Drug Branch for Breast Cancer (IDBBC). Mature results of a randomized phase II multicenter study of exemestane versus tamoxifen as first-line hormone therapy for postmenopausal women with metastatic breast cancer. Ann Oncol. 2003 Sep;14(9):1391-8. doi: 10.1093/annonc/mdg362.

Pfizer, Inc. Palbociclib (PD-0332991): Investigator's Brochure. N.p.: Pfizer, 2015. Print.

Other Publications:

Early Breast Cancer Trialists' Collaborative Group (EBCTCG); Peto R, Davies C, Godwin J, Gray R, Pan HC, Clarke M, Cutter D, Darby S, McGale P, Taylor C, Wang YC, Bergh J, Di Leo A, Albain K, Swain S, Piccart M, Pritchard K. Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet. 2012 Feb 4;379(9814):432-44. doi: 10.1016/S0140-6736(11)61625-5. Epub 2011 Dec 5.

Welch HG, Gorski DH, Albertsen PC. Trends in Metastatic Breast and Prostate Cancer--Lessons in Cancer Dynamics. N Engl J Med. 2015 Oct 29;373(18):1685-7. doi: 10.1056/NEJMp1510443. No abstract available.

Baselga J, Cortes J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, Clark E, Benyunes MC, Ross G, Swain SM; CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012 Jan 12;366(2):109-19. doi: 10.1056/NEJMoa1113216. Epub 2011 Dec 7.

Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Heeson S, Clark E, Ross G, Benyunes MC, Cortes J; CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015 Feb 19;372(8):724-34. doi: 10.1056/NEJMoa1413513.

Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, Forman D, Bray F. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013 Apr;49(6):1374-403. doi: 10.1016/j.ejca.2012.12.027. Epub 2013 Feb 26.

Sherr CJ, Roberts JM. CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev. 1999 Jun 15;13(12):1501-12. doi: 10.1101/gad.13.12.1501. No abstract available.

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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Peddi PF, Slamon DJ. Frontiers in HER2-positive breast cancer in 2020. Curr Opin Obstet Gynecol. 2021 Feb 1;33(1):48-52. doi: 10.1097/GCO.0000000000000677.

• Responsible Party: Alliance Foundation Trials, LLC.
• ClinicalTrials.gov Identifier: NCT02947685
• Other Study ID Numbers: AFT-38
• First Posted: October 28, 2016
• Last Update Posted: May 30, 2023
• Last Verified: April 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Alliance Foundation Trials, LLC.:

breast cancer; malignant tumor of the breast; HER2+; HR+; metastatic breast cancer

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Trastuzumab; Pertuzumab; Letrozole; Fulvestrant; Palbociclib; Anastrozole; Exemestane; Antineoplastic Agents, Immunological; Antineoplastic Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Estrogen Receptor Antagonists; Protein Kinase Inhibitors