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Palbociclib (PD-0332991) Combined With Fulvestrant In Hormone Receptor+ HER2-Negative Metastatic Breast Cancer After Endocrine Failure (PALOMA-3)

Primary Purpose

Metastatic Breast Cancer

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Palbociclib

Fulvestrant

Placebo

Fulvestrant

About this trial

This is an interventional treatment trial for Metastatic Breast Cancer focused on measuring Palbociclib (PD-0332991), Fulvestrant, Goserelin, Hormone receptor-+, HER2-negative, Prior Endocrine treatment, any menopausal status, PALOMA-3

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

Women 18 years or older with metastatic or locally advanced disease, not amenable to curative therapy
Confirmed diagnosis of HR+/HER2- breast cancer
Any menopausal status
Progressed within 12 months from prior adjuvant or progressed within 1 month from prior advanced/metastatic endocrine breast cancer therapy
On an LHRH agonist for at least 28 days, if pre-/peri-menopausal, and willing to switch to goserelin (Zoladex ®) at time of randomization.
Measurable disease defined by RECIST version 1.1, or bone-only disease
Eastern Cooperative Oncology Group (ECOG) PS 0-1
Adequate organ and marrow function, resolution of all toxic effects of prior therapy or surgical procedures
Patient must agree to provide tumor tissue from metastatic tissue at baseline

Exclusion Criteria:

Prior treatment with any CDK inhibitor, fulvestrant, everolimus, or agent that inhibits the PI3K-mTOR pathway
Patients with extensive advanced/metastatic, symptomatic visceral disease, or known uncontrolled or symptomatic CNS metastases
Major surgery or any anti-cancer therapy within 2 weeks of randomization
Prior stem cell or bone marrow transplantation
Use of potent CYP3A4 inhibitors or inducers

Sites / Locations

University of Alabama at Birmingham, The Kirklin Clinic
UAB Hospital-Investigational Drug Service
University of Alabama at Birmingham
Southern Cancer Center, PC
Southern Cancer Center, PC
Southern Cancer Center, PC
Southern Cancer Center,PC
Arizona Center for Cancer Care
Ironwood Physicians P.C dba Ironwood Cancer & Research Centers
Arizona Oncology Associates, PC- HAL
Ironwood Physicians P.C dba Ironwood Cancer & Research Centers
Palo Verde Hematology Oncology
Arizona Center for Cancer Care
Western Regional Medical Center, Inc.
Ironwood Physicians P.C dba Ironwood Cancer & Research Centers
Ironwood Physicians P.C dba Ironwood Cancer & Research Centers
Arizona Oncology Associates, PC- HAL
Arizona Oncology Associates, PC- HAL
Arizona Center for Cancer Care
The University of Arizona Cancer Center- North Campus
The University of Arizona Cancer Center
CBCC Global Research Inc. at Comprehensive Blood and Cancer Center
Administrative Management Only: Translational Research Management
City of Hope
St. Jude Hospital Yorba Linda DBA St. Joseph Heritage Healthcare
Global Research Management
UC San Diego Medical Center-La Jolla
UC San Diego Moores Cancer Center
Keck Hospital of USC
LAC & USC Medical Center
USC/Norris Comprehensive Cancer Center
UCLA Hematology Oncology
Breastlink Medical Group, Inc.
Hematology Oncology Medical Group of Orange County, Inc. (HOMG)
The Center for Cancer Prevention and Treatment at St. Joseph Hospital of Orange
UCLA Hematology/Oncology - Pasadena
UC San Diego Medical Center-Hillcrest
University of California, San Francisco: Helen Diller Comprehensive Cancer Center
San Luis Obispo Oncology and Hematology Health Center/Pacific Central Coast Health Centers
Breastlink Medical Group, Inc.
Central Coast Medical Oncology Corporation
UCLA Hematology/Oncology - Santa Monica
City of Hope
Torrance Health Association, DBA Torrance Memorial Physician Network/Cancer Care Associates
Torrance Memorial Physician Network-Cancer Care
Wellness Oncology & Hematology
UCLA Hematology - Oncology Clinic - Westlake Village
ATTN - Research Pharmacist
University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)
University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)
Mount Sinai Medical Center- Aventura
Sylvester Comprehensive Cancer Center Deerfield Beach
University of Miami Hospitals and Clinics (UHMC) Sylvester at Deerfield Beach
Holy Cross Hospital/Michael and Dianne Bienes Comprehensive Cancer Center
Memorial Breast Cancer Center at Memorial Regional Hospital
Memorial Cancer Institute at Memorial Regional Hospital
Memorial Regional Hospital
Mount Sinai Comprehensive Cancer Center
Mount Sinai Medical Center
University of Miami Hospitals & Clinics
Orlando Health
Orlando Health Cancer Institute
Memorial Breast Cancer Center at Memorial Hospital West
Memorial Cancer Institute at Memorial Hospital West
Memorial Hospital West
Sylvester at Plantation
Piedmont Cancer Institute, PC
Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital
Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital
Piedmont Cancer Institute, PC
Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital
Northwest Georgia Oncology Centers, PC
Rush University Medical Center
Cancer Treatment Centers of America at Midwestern Regional Medical Center
Maine Center for Cancer Medicine, dba: New England Cancer Specialists
Maine Center for Cancer Medicine, dba: New England Cancer Specialists
Maine Center for Cancer Medicine, dba: New England Cancer Specialists
Sidney Kimmel Comprehensive Cancer Center (SKCCC) at Johns Hopkins
Sidney Kimmel Comprehensive Cancer Center (SKCCC) at Johns Hopkins, Green Spring Station
University of Michigan Health System/Comprehensive Cancer Center
Cancer and Hematology Centers of Western Michigan
Fairview Southdale Oncology Clinic
University of Minnesota Medical Center, Fairview
University of Minnesota Physicians, Masonic Cancer Center
Mercy Clinic St. Louis Cancer and Breast Institute
Mercy Ministry Office
Mercy Clinic St. Louis Cancer and Breast Institute
Mercy Hospital St. Louis
Mercy Hospital St.Louis- David C. Pratt Cancer Center
Comprehensive Cancer Centers of Nevada
Comprehensive Cancer Centers of Nevada
Comprehensive Cancer Centers of Nevada
Comprehensive Cancer Centers of Nevada
Comprehensive Cancer Centers of Nevada
Rutgers Cancer Institute of New Jersey
CareMount Medical
ProHEALTHCARE Associates, LLP
CareMount Medical
Northern Westchester Hospital
Hope Women's Cancer Centers
Mission Hospital, Inc.
UPMC Cancer Center, Monroeville
Hospital of the University of Pennsylvania
Thomas Jefferson University
Magee Womens Hospital of UPMC
University of Pittsburgh Medical Center, William M. Cooper Pavilion, Hillman Cancer Center
The Jones Clinic, PC
Texas Oncology- Dallas Presbyterian Hospital
Investigational Products Center (IPC)
US Oncology Investigational Products Center (IPC)
US Oncology lnvestigational Products Center (IPC)
Texas Oncology- Longview Cancer Center
Texas Oncology- McAllen South Second Street
Cancer Care Centers of South Texas
Cancer Care Centers of South Texas
Cancer Care Centers of South Texas
Texas Oncology- Tyler
Texas Oncology- Weslaco
Huntsman Cancer Hospital
Huntsman Cancer Institute
Virginia Cancer Specialists, PC
Emily Couric Clinical Cancer Center
Inova Medical Group
Inova Schar Cancer Institute
Virginia Cancer Specialists, PC
Virginia Cancer Specialists, PC
Virginia Oncology Associates
Virginia Oncology Associates
Shenandoah Oncology, P.C.
Swedish Cancer Institute
Swedish Medical Center First Hill IDS Pharmacy
Swedish Medical Center
Columbia St. Mary's
Columbia St. Mary's
Bankstown - Lidcombe Hospital
Calvary Mater Newcastle
River City Pharmacy
Sunshine Coast Hospital and Health Service
Icon Cancer Care Southport
Cabrini Brighton
Monash Medical Centre
Peninsula and Southeast Oncology
Barwon Health, University Hospital Geelong
Cabrini Hospital
Peter MacCallum Cancer Centre Pharmacy
Peter MacCallum Cancer Centre
Sunshine Hospital Clinical Trials Pharmacy
Sunshine Hospital
Fiona Stanley Hospital - Cancer Centre
UZ Antwerpen
Clinique Saint-Pierre
Institut Jules Bordet
Grand Hôpital de Charleroi - Site Notre Dame
INDC Entité Jolimontoise - CH de Jolimont-Lobbes
CHWaPi - Site IMC
C.H. de l'Ardenne - site Libramont
Hopital Erasme
Imelda Ziekenhuis
Cliniques Universitaires Saint-Luc
UZ Leuven - Campus Gasthuisberg
CHU UCL Namur - Site Sainte-Elisabeth
GZA Ziekenhuizen - Campus St Augustinus
British Columbia Cancer Agency - Sindi Ahluwalia Hawkins Centre for the Southern Interior
British Columbia Cancer Agency - Fraser Valley Centre
Royal Victoria Regional Health Centre
Cancer Centre of Southeastern Ontario @ Kingston Health Sciences Centre
Lakeridge Health Oshawa, R.S. McLaughlin Durham Regional Cancer Centre
The Ottawa Hospital Cancer Centre, General Campus
Niagara Health System Walker Family Cancer Center
Toronto East General Hospital
Sunnybrook Research Institute
Princess Margaret Cancer Centre
Jewish General Hospital
Universitaetsklinikum Leipzig AoeR
Zentrum fuer Radiologie und Nuklearmedizin am Johannisplatz
Klinikum der Universität München
Klinikum der Universität München
Bon Secours Hospital
Azienda Sanitaria Firenze, c/o Ospedale S. M. Annunziata Farmacia Interna
S.O.C. Oncologia Medica I, Azienda Sanitaria Firenze, c/o Ospedale S. M. Annunziata
SSD Oncologia Medica Addarii-Zamagni A.O.U. di Bologna Policlinico S. Orsola Malpighi
U.O. di Oncologia Medica P.O. Policlinico G. Rodolico"
Azienda U.L.S.S. n. 21 di Legnago, Presidio Ospedaliero Mater Salutis
Farmacia Ospedaliera-Azienda U.L.S.S. n. 21 di Legnago
IRST, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
Farmacia IRCCS Ospedale San Raffaele
IRCCS Ospedale S. Raffaele
Fondazione IRCCS Istituto Nazionale dei Tumori
Istituto Europeo di Oncologia
Servizio di Farmacia - Istituto Europeo di Oncologia
Policlinico di Modena Dipartimento ad attivita integrata di Oncologia,
IRCCS Istituto Nazionale per lo Studio e la Cura dei Tumori
Farmacia - Fondazione Policlinico Universitario A. Gemelli
Fondazione Policlinico Universitario A. Gemelli
S.C. Oncologia, A.O.S. Maria
Aichi Cancer Center Hospital
National Cancer Center Hospital East
National Hospital Organization Shikoku Cancer Center
Saitama Cancer Center
Chiba Cancer Center
National Hospital Organization Kyushu Cancer Center
Hakuaikai Medical Corporation Sagara Hospital
National Hospital Organization
National Cancer Center
Seoul National University Bundang Hospital
Seoul National University Hospital
Asan medical Center
Samsung Medical Center
Academisch Ziekenhuis Maastricht
Orbis Medisch Centrum
TweeSteden Ziekenhuis
Haga Ziekenhuis
Leids Universitair Medisch Centrum
Ikazia Ziekenhuis
Champalimaud Cancer Center/ Breast Unit
Instituto Português de Oncologia
Spitalul Clinic CF nr.2 Bucuresti
Spitalul Municipal Ploiesti
Spitalul Judetean de Urgente "Sf. Ioan cel Nou"
Spitalul Clinic Judetean Mures
OGBUZ Belgorod Oncology Dispensary
OGBUZ Belgorod Oncology Dispensary
GBUZ Leningrad regional oncological dispensary
GBUZ Republican Clinical Oncology Dispensary of Ministry of Health of the Republic of Bashkortostan
FGBUZ Clinical Hospital 101 of the Federal Medical and Biological Agency"
GBUZ of Stavropol Territory "Pyatigorsk Oncology Dispensary"
GBUZ Chelyabinsk regional clinical center of oncology and nuclear medicine
FSBSI Russian Cancer Research Center n.a.NN Blokhin
Saint Petersburg GBUZ "City Clinical Oncology Dispensary"
Saint Petersburg GBUZ City Clinical Oncology Dispensary
GBUZ of Stavropol Territory "Stavropol Regional Clinical Oncology Dispensary"
FGBU Russian Research Center for Radiology and Surgical Technologies
National Cheng Kung University Hospital
National Taiwan University Hospital
Ege University Medical Faculty
Oblasne komunalne nekomertsiine pidpryiemstvo "Bukovynskyi klinichnyi onkolohichnyi tsentr"
Komunalnyi zaklad 'Miska klinichna likarnia No.4' Dniprovskoi miskoi rady,
Komunalne nekomertsiyne pidpryiemstvo "Oblasnyi
KNP Lvivskoi oblasnoi rady Lvivskyi onkolohichnyi
Komunalna ustanova "Odeska oblasna klinichna likarnia"
Podilskyi rehionalnyi tsentr onkolohii,
Queen Alexandra Hospital, Portsmouth Hospitals NHS Trust Portsmouth Haematology and Oncology Centre
Velindre Cancer Centre
Royal Hallamshire Hospital
Sheffield Teaching Hospitals NHS Foundation Trust, Weston Park Hospital
The Royal Marsden NHS Foundation Trust
The Royal Marsden NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm A

Arm B

Arm Description

Given until objective progression, symptomatic deterioration, unacceptable toxicity, death, or withdrawal of consent, whichever occurs first.

Outcomes

Primary Outcome Measures

Progression-Free Survival (PFS) as Assessed by the Investigator

PFS is the time from the date of randomization to the date of the first documentation of objective progression of disease (PD)or death due to any cause in absence of documented PD. Participants lacking an evaluation of tumor response after randomization had their PFS time censored on the date of randomization with the duration of a day. Participants with documentation of PD or death after a long interval (2 or more incomplete or non-evaluable assessments) since the last tumor assessment were censored at the time of last objective assessment that did not show PD. The length of PFS was calculated as PFS time (months) =[progression/death date(censor date) - randomization date + 1]/30.4. Progression is defined using Response Evaluation Criteria in Solid Tumors(RECIST v1.1) a 20% increase in the sum of diameters of target lesions and the sum must also demonstrate an absolute increase of at least 5mm or unequivocal progression of existing non-target lesions or the appearance of new lesions.

Secondary Outcome Measures

Overall Survival (OS) - Number of Participants Who Died

OS is defined as the time from date of randomization to date of death due to any cause. In the absence of confirmation of death, survival time was censored to last date the participant was known to be alive. For participants lacking survival data beyond the date of their last follow-up, the OS time was censored on the last date they were known to be alive. Participants lacking survival data beyond randomization were to have their OS times be censored at randomization. The length of OS was calculated as OS time (months) = [death date (censor date) - randomization date + 1]/30.4. No inferential statistical analysis were done because of the immaturity of the OS data.

Objective Response (OR)

OR is defined as the overall complete response (CR) or partial response (PR) according to the RECIST version 1.1 Objective Response Rate (ORR) is defined as the proportion of participants with CR or PR relative to all randomized participants and randomized participants with measurable disease at baseline. Participants who do not have on-study radiographic tumor re-evaluation, who received anti-tumor treatment other than the study medication prior to reaching a CR or PR, or who died, progressed, or dropped out for any reason prior to reaching a CR or PR were counted as non-responders in the assessment of ORR. Per response evaluation criteria in solid tumors criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), ≥30% decrease in the sum of the longest diameter of target lesions (longest for non-nodal and short axis for nodal target lesions); Overall Response (OR) = CR + PR.

Duration of Response (DR)

DR is defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of disease progression or to death due to any cause, whichever occurs first. If tumor progression data included more than 1 date, the first date was used. DR was calculated as [the date response ended (ie, date of PD or death) - first CR or PR date + 1)]/30.4. Kaplan-Meier estimate of median of the DR is provided below. No inferential statistical analysis were done for DR. The DR was only calculated for the participants with a CR or PR.

Clinical Benefit Response (CBR)

CBR is defined as the overall complete response (CR), partial response (PR) , or stable disease (SD) ≥24 weeks according to the RECIST version 1.1. Clinical Benefit Response Rate (CBRR) is defined as the proportion of participants with CR, PR, or SD ≥24 weeks relative to all randomized participants and randomized participants with measurable disease at baseline. Participants who do not have on-study radiographic tumor re-evaluation, who received antitumor treatment other than the study medication prior to reaching a CR or PR, a best response of SD ≥24 weeks, or who died, progressed, or dropped out for any reason prior to reaching a CR or PR and a best response of SD ≥24 weeks was counted as non-responders in the assessment of CBR. Per RECIST v1.1 for target lesions and assessed by MRI: CR, disappearance of all target lesions; PR, ≥30% decrease in the sum of the longest diameter of target lesions; OR = CR + PR.

Survival Probabilities at Months 12, 24 and 36

One-, Two- or Three-year Survival Probability is defined as the probability of survival 1 year, 2 or 3 years after the date of randomization based on the Kaplan-Meier estimate. Survival time was censored to last date the participant is known to be alive.

Observed Plasma Trough Concentration (Ctrough) for Palbociclib

Ctrough for palbociclib (if applicable). The method of dispersion applied here is "percent coefficient of variation" (%CV).

Ctrough for Fulvestrant

Ctrough for Fulvestrant (if applicable). The method of dispersion applied here is "percent coefficient of variation" (%CV).

Ctrough for Goserelin

Cmin for goserelin (if applicable). The method of dispersion applied here is "percent coefficient of variation" (%CV).

Change From Baseline Between Treatment Comparison in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Functional Scale Scores

The EORTC-QLQ-C30 is a 30-item questionnaire composed of five multi-item functional subscales (physical, role, emotional, cognitive , and social functioning), three multi-item symptom scales (fatigue, nausea/vomiting, and pain), a global quality of life (QOL) subscale, and six single item symptom scales assessing other cancer-related symptoms (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and the financial impact of cancer). The questionnaire employs 28 4-point Likert scales with responses from "not at all" to "very much" and two 7-point Likert scales for global health and overall QOL. Responses to all items are then converted to a 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represents more severe symptoms. A 10-point or higher change in scores from baseline is considered clinically significant.

Change From Baseline Between Treatment Comparison in EORTC QLQ-C30 Symptom Scale Scores

Change From Baseline Between Treatment Comparison in European Organization for Research and Treatment of Cancer Breast Cancer Module (EORTC QLQ BR23) Functional Scale Scores

The EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual functioning, sexual enjoyment, future perspective) and four symptom scales (systemic side effects, breast symptoms, arm symptoms, upset by hair loss). QLQ-BR23 questionnaire employs 4-point scales with responses from 'not at all' to 'very much'. All scores are converted to a 0 to 100 scale. For functional scales, higher scores represent a better level of functioning.

Change From Baseline Between Treatment Comparison in EORTC QLQ BR23 Symptom Scale Scores

The EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual functioning, sexual enjoyment, future perspective) and four symptom scales (systemic side effects, breast symptoms, arm symptoms, upset by hair loss). QLQ-BR23 questionnaire employs 4-point scales with responses from 'not at all' to 'very much'. All scores are converted to a 0 to 100 scale. For symptom-oriented scales, a higher score represent more severe symptoms.

Change From Baseline Between Treatment Comparison in EuroQoL 5D (EQ-5D)- Health Index Scores

The EuroQol-5D (version 3L) is a brief self-administered, validated instrument consisting of 2 parts. The first part consists of 5 descriptors of current health state (mobility, self care, usual activities, pain/discomfort, and anxiety/ depression); a participant is asked to rate each state on a three level scale (1=no problem, 2=some problem, and 3=extreme problem) with higher levels indicating greater severity/ impairment Published weights are available that allow for the creation of a single summary score called the EQ-5D index, which basically ranges from 0 to 1 with low scores representing a higher level of dysfunction and 1 as perfect health. The second part consists of the EQ-5D general health status as measured by a visual analog scale (EQ-5D VAS). EQ-5D VAS measures the participant's self-rated health status on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state).

Change From Baseline Between Treatment Comparison in EQ-5D Visual Analog Scale (VAS) Scores Scale

The EuroQol-5D (version 3L) is a brief self-administered, validated instrument consisting of 2 parts. The second part consists of the EQ-5D general health status as measured by a visual analog scale (EQ-5D VAS). EQ-5D VAS measures the participant's self-rated health status on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state).

Time to Deterioration (TTD)

A time to event analysis was pre-specified for pain. An analysis of TTD in pain defined as time between baseline and first occurrence of increase of ≥10 points in pain. Deterioration will be defined increase in score of 10 points or greater from baseline. The Kaplan-Meier estimates of quartiles (time to deterioration) with 95% CI is mentioned below.

Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs; All Causalities)

An AE is any untoward medical occurrence in a clinical investigation patient administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An SAE is any untoward medical occurrence at any dose that results in death; is life-threatening; requires hospitalization; results in persistent or significant disability or in congenital anomaly/birth defect. Severity will be graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0.

Full Information

NCT ID

NCT01942135

First Posted

September 10, 2013

Last Updated

April 25, 2023

Sponsor

Pfizer

Collaborators

AstraZeneca

1. Study Identification

Unique Protocol Identification Number

NCT01942135

Brief Title

Palbociclib (PD-0332991) Combined With Fulvestrant In Hormone Receptor+ HER2-Negative Metastatic Breast Cancer After Endocrine Failure (PALOMA-3)

Official Title

MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE 3 TRIAL OF FULVESTRANT (FASLODEX (REGISTERED)). WITH OR WITHOUT PD-0332991 (PALBOCICLIB) +/- GOSERELIN IN WOMEN WITH HORMONE RECEPTOR-POSITIVE, HER2-NEGATIVE METASTATIC BREAST CANCER WHOSE DISEASE PROGRESSED AFTER PRIOR ENDOCRINE THERAPY

Study Type

Interventional

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Completed

Study Start Date

September 26, 2013 (Actual)

Primary Completion Date

December 5, 2014 (Actual)

Study Completion Date

September 28, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pfizer

Collaborators

AstraZeneca

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The study is a randomized, double blind, placebo controlled, Phase 3 clinical trial with the primary objective of demonstrating the superiority of palbociclib in combination with fulvestrant (Faslodex®) over fulvestrant alone in prolonging PFS in women with HR+, HER2 negative metastatic breast cancer whose disease has progressed after prior endocrine therapy. The safety between the two treatment arms will also be compared. During study treatment, pre- and perimenopausal women must be receiving therapy with the LHRH agonist goserelin (Zoladex® or generic).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic Breast Cancer

Keywords

Palbociclib (PD-0332991), Fulvestrant, Goserelin, Hormone receptor-+, HER2-negative, Prior Endocrine treatment, any menopausal status, PALOMA-3

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

521 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A

Arm Type

Experimental

Arm Description

Given until objective progression, symptomatic deterioration, unacceptable toxicity, death, or withdrawal of consent, whichever occurs first.

Arm Title

Arm B

Arm Type

Active Comparator

Arm Description

Given until objective progression, symptomatic deterioration, unacceptable toxicity, death, or withdrawal of consent, whichever occurs first.

Intervention Type

Drug

Intervention Name(s)

Palbociclib

Intervention Description

Palbociclib 125 mg/day orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle.

Intervention Type

Drug

Intervention Name(s)

Fulvestrant

Intervention Description

Fulvestrant 500 mg intramuscularly on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle.

Intervention Type

Drug

Intervention Name(s)

Fulvestrant

Intervention Description

Fulvestrant 500 mg intramuscularly on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle.

Primary Outcome Measure Information:

Title

Progression-Free Survival (PFS) as Assessed by the Investigator

Description

Time Frame

From randomization date to date of first documentation of progression or death (assessed up to 12 months)

Secondary Outcome Measure Information:

Title

Overall Survival (OS) - Number of Participants Who Died

Description

Time Frame

From randomization until death (up to approximately 36 months)

Title

Objective Response (OR)

Description

Time Frame

From randomization until end of treatment (assessed up to 12 months)

Title

Duration of Response (DR)

Description

Time Frame

From randomization until end of treatment (assessed up to 12 months)

Title

Clinical Benefit Response (CBR)

Description

Time Frame

From randomization until end of treatment (assessed up to 12 months)

Title

Survival Probabilities at Months 12, 24 and 36

Description

Time Frame

From randomization until death (assessed up to 36 months)

Title

Observed Plasma Trough Concentration (Ctrough) for Palbociclib

Description

Ctrough for palbociclib (if applicable). The method of dispersion applied here is "percent coefficient of variation" (%CV).

Time Frame

Cycle 1/Day 15 and Cycle 2/Day 15

Title

Ctrough for Fulvestrant

Description

Ctrough for Fulvestrant (if applicable). The method of dispersion applied here is "percent coefficient of variation" (%CV).

Time Frame

Cycles 2/Day 1 and Cycle 3/Day 1

Title

Ctrough for Goserelin

Description

Cmin for goserelin (if applicable). The method of dispersion applied here is "percent coefficient of variation" (%CV).

Time Frame

Cycles 2/ Day 1 and Cycle 3/ Day 1

Title

Change From Baseline Between Treatment Comparison in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Functional Scale Scores

Description

Time Frame