Clinical trial NCT02297438: A Study Of Palbociclib (PD-0332991) + Letrozole VS. Placebo+ Letrozole For 1st Line Treatment Of Asian Postmenopausal Women With ER+/HER2- Advanced Breast Cancer [PALOMA-4]
Official title: A MULTICENTER, RANDOMIZED, DOUBLE-BLIND PHASE 3 STUDY OF PALBOCICLIB (ORAL CDK 4/6 INHIBITOR) PLUS LETROZOLE VERSUS PLACEBO PLUS LETROZOLE FOR THE TREATMENT OF PREVIOUSLY UNTREATED ASIAN POSTMENOPAUSAL WOMEN WITH ER (+), HER2 (-) ADVANCED BREAST CANCER
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Breast Neoplasms
Keywords: breast cancer
postmenopausal women
estrogen-receptor positive
HER2 negative
locoregionally recurrent
metastatic
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2014-11-21
Enrollment: 340
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study is designed to compare the clinical benefit following treatment with letrozole in combination with Palbociclib versus letrozole in combination with placebo in Asian postmenopausal women with ER(+)/HER2(-) advanced breast cancer who have not received prior systemic anti cancer therapies for their advanced/metastatic disease.


Eligibility criteria: Inclusion Criteria:

* Adult Asian women with locoregionally recurrent or metastatic disease not amenable to curative therapy
* Confirmed diagnosis of ER positive breast cancer
* No prior systemic anti-cancer therapy for advanced ER+ disease
* Postmenopausal women
* Measurable disease as per Response Evaluation Criterion in Solid Tumors \[RECIST\] or bone-only disease
* Eastern Cooperative Oncology Group \[ECOG\] 0-1
* Adequate organ and marrow function
* Patient must agree to provide tumor tissue

Exclusion Criteria:

* Confirmed diagnosis of HER2 positive disease
* Patients with advanced, symptomatic, visceral spread that are at risk of life threatening complication in the short term
* Known uncontrolled or symptomatic CNS metastases
* Prior neoadjuvant or adjuvant treatment with a non steroidal aromatase inhibitor (ie, anastrozole or letrozole) with disease recurrence while on or within 12 months of completing treatment
* Prior treatment with any CDK 4/6 inhibitor

Primary outcomes:
measure: Progression-Free Survival (PFS) Based on Investigator's Assessment
timeFrame: Randomization up to 65 months
Secondary outcomes:
measure: Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR)
timeFrame: Randomization up to 65 months
measure: Percentage of Participants Wiht Objective Response (OR) Based on Investigator Assessment
timeFrame: Randomization up to 65 months
measure: Percentage of Participants With Objective Response (OR) Based on Investigator Assessment (Participants With Measureable Disease at Baseline)
timeFrame: Randomization up to 65 months
measure: Percentage of Participants With Objective Response (OR) Based on Blinded Independent Central Review (BICR)
timeFrame: Randomization up to 65 months
measure: Percentage of Participants With Objective Response (OR) Based on Blinded Independent Central Review (BICR) (Participants With Measureable Disease at Baseline)
timeFrame: Randomization up to 65 months
measure: Duration of Response (DOR) Based on Investigator Assessment (Participants With Objective Disease Response)
timeFrame: Randomization up to 65 months
measure: Duration of Response (DOR) Based on Blinded Independent Central Review (BICR) (Participants With Objective Disease Response)
timeFrame: Randomization up to 65 months
measure: Percentage of Participants With Disease Control/Clinical Benefit Response (DC/CBR) Based on Investigator Assessment
timeFrame: Randomization up to 65 months
measure: Percentage of Participants With Disease Control/Clinical Benefit Response (DC/CBR) Based on Investigator Assessment (Participants With Measureable Disease at Baseline)
timeFrame: Randomization up to 65 months
measure: Percentage of Participants With Disease Control/Clinical Benefit Response (DC/CBR) Based on Blinded Independent Central Review (BICR)
timeFrame: Randomization up to 65 months
measure: Percentage of Participants With Disease Control/Clinical Benefit Response (DC/CBR) Based on Blinded Independent Central Review (BICR) (Participants With Measureable Disease at Baseline)
timeFrame: Randomization up to 65 months
measure: Overall Survival (OS)
timeFrame: Randomization up to 65 months
measure: 1-Year, 2-Year and 3-Year Survival Probability
timeFrame: Randomization up to 65 months
measure: Number of Participants With Treatment-Emergent Adverse Events (All Causalities)
timeFrame: Randomization up to 65 months
measure: Number of Participants With Treatment-Emergent Adverse Events (Treatment Related)
timeFrame: Randomization up to 65 months
measure: Number of Participants With Postbaseline Laboratory Abnormalities of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 (Participants With Baseline Laboratory Abnormalities of CTCAE Grade <=2) - Hematology
timeFrame: Randomization up to 65 months
measure: Number of Participants With Postbaseline Laboratory Abnormalities of Common Terminology Criteria for Adverse Events(CTCAE) Grade 3 or 4 (Participants With Baseline Laboratory Abnormalities of CTCAE Grade <=2) - Chemistry
timeFrame: Randomization up to 65 months
measure: Trough Plasma Concentration of Palbociclib
timeFrame: Pre-dose on Day 14 of Cycle 1 and Cycle 2
measure: Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
timeFrame: Baseline up to Cycle 65 Day 1
measure: Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
timeFrame: Baseline up to Cycle 65 Day 1
measure: Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
timeFrame: Baseline up to Cycle 65 Day 1
measure: Median Baseline Percent (%) Positive Cells for Ki67
timeFrame: Baseline
measure: Number of Participants With Detection in Estrogen Receptor (ER)
timeFrame: Baseline
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College/Medical Oncology Department
state: Anhui
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital/Medical Oncology Department
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center
state: Guangdong
city: Guangzhou
country: China
facility: Zhongshan Ophthalmic Center,Sun Yat-Sen University
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Breast Tumor Center, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
state: Guangdong
city: Shijiazhuang
country: China
facility: Fourth Hospital of Hebei Medical University
state: Hebei
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital/Oncology Department
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: Hunan Provincial Tumor Hospital/Breast Internal Medicine Department
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Changchun
country: China
facility: Jilin Provincial Cancer Hospital
state: Jilin
city: Shenyang
country: China
facility: The First Hospital of China Medical University/Oncology Department
state: Liaoning
city: Shenyang
country: China
facility: Liaoning Province Cancer Hospital
state: Liaoning
city: Shanghai
country: China
facility: Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Cancer Hospital/Breast cancer department
state: Tianjin
city: Kunming
country: China
facility: The Tumor Hospital of Yunnan Province
state: Yunnan
city: Hangzhou
country: China
facility: The First Affiliated Hospital of College of Medicine, Zhejiang University
state: Zhejiang
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital of College of Medicine of Zhejiang University, Center for Oncology
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Beijing
country: China
facility: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
city: Beijing
country: China
facility: 307 Hospital of PLA
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Beijing
country: China
facility: Peking University Third Hospital/Department of Oncology
city: Beijing
country: China
facility: Chinese PLA General Hospital/Oncology
city: Chongqing City
country: China
facility: Oncology Department, the Second Affiliated Hospital of Third Military Medical University, PLA
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Hong Kong
country: Hong Kong
facility: Block R
city: Hong Kong
country: Hong Kong
facility: Department of Clinical Oncology
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: HongKong
country: Hong Kong
facility: Queen Mary Hospital
city: Singapore
country: Singapore
facility: Raffles Cancer Centre
city: Singapore
country: Singapore
facility: Parkway Cancer Centre
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital / Internal Medicine
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Mackay Memorial Hospital
city: Taipei
country: Taiwan
facility: Taipei Medical University Hospital/ Department of Surgery
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital/Surgery Department
city: Taipei
country: Taiwan
facility: Koo Foundation, Sun Yat-Sen Cancer Center
city: Taipei
country: Taiwan
facility: Taipei Municipal Wanfang Hospital (Managed by Taipei Medical University )
city: Pathumwan
country: Thailand
facility: King Chulalongkorn Memorial Hospital
state: Bangkok
city: Patumwan
country: Thailand
facility: Chula Clinical Research Center (Chula CRC)
state: Bangkok
city: Muang
country: Thailand
facility: Division of Therapeutic Radiology and Oncology, Department of Radiology
state: Chiang MAI
city: Muang
country: Thailand
facility: Department of Medicine, Faculty of Medicine, Naresuan University
state: Phitsanulok
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital, Mahidol University
state: Ratchathevi
city: Bangkok
country: Thailand
facility: Oncology Unit, Department of Internal Medicine, Phramongkutklao Hospital
city: Bangkok
country: Thailand
facility: Division of Medical Oncology, Department of Medicine,
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Xu B, Hu X, Li W, Sun T, Shen K, Wang S, Cheng Y, Zhang Q, Cui S, Tong Z, Geng C, Song E, Huang CS, Sriuranpong V, Ngan RKC, Chia YH, Wang X, Zhao H. Palbociclib plus letrozole versus placebo plus letrozole in Asian postmenopausal women with oestrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: Primary results from PALOMA-4. Eur J Cancer. 2022 Nov;175:236-245. doi: 10.1016/j.ejca.2022.08.012. Epub 2022 Sep 22.