NCT01740427 · CITED IN SOURCE DOCUMENTS

A Study of Palbociclib (PD-0332991) + Letrozole vs. Letrozole For 1st Line Treatment Of Postmenopausal Women With ER+/HER2- Advanced Breast Cancer (PALOMA-2)

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2024-11-14

The study is designed to compare the clinical benefit following treatment with letrozole in combination with PD-0332991 versus letrozole in combination with placebo in postmenopausal women with ER(+)/HER2(-) advanced breast cancer who have not received prior systemic anti cancer therapies for their advanced/metastatic disease.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

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

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outcome · POSTED

Objective Response as Assessed by the Investigator

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outcome · POSTED

Objective Response: Participants With Measurable Disease at Baseline as Assessed by the Investigator

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outcome · POSTED

Duration of Response (DR)

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outcome · POSTED

Disease Control (DC)/Clinical Benefit Response (CBR)

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outcome · POSTED

PFS by Tumor Tissue Biomarkers Status, Including Genes (eg, Copy Numbers of CCND1, CDKN2A), Proteins (eg, Ki67, pRb), and RNA Expression (eg, cdk4, cdk6)

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outcome · POSTED

Corrected QT Interval (QTc) Time-Matched Change From Baseline on Cycle 1 Day 14

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outcome · POSTED

Percentage of Participants With Corrected QT Interval (QTc)

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outcome · POSTED

Observed Plasma Trough Concentration (Ctrough) at Steady-State

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outcome · POSTED

Change From Baseline Between Treatment Comparison in Euro Quality of Life (EQ-5D) Index

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outcome · POSTED

Change From Baseline Between Treatment Comparison in Functional Assessment of Cancer Therapy-Breast (FACT-B)

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outcome · POSTED

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

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outcome · POSTED

Overall Survival (OS): Primary Analysis

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outcome · POSTED

Overall Survival (OS): Final Analysis

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outcome · POSTED

Survival Probability at 1 Year, 2 Year and 3 Year

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outcome · POSTED

Number of Participants With Laboratory Abnormalities by Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Adult 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 \[ECOG\] 0-2 * 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 (neo)adjuvant treatment with letrozole or anastrozole with DFI ≤ 12-months from completion of treatment. * Prior treatment with any CDK 4/6 inhibitor.
gender Based: true
healthy Volunteers: false
minimum Age: 18 Years
sex: FEMALE
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
PD-0332991, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment in combination with Letrozole, 2.5mg, orally once daily (continuously).
intervention Names
Drug: PD-0332991
Drug: Letrozole
label
PD-0332991 + Letrozole
type
EXPERIMENTAL
description
Placebo, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment in combination with Letrozole, 2.5mg, orally once daily (continuously).
intervention Names
Drug: Placebo
Drug: Letrozole
label
Placebo + Letrozole
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
PD-0332991 + Letrozole
description
PD-0332991, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment
name
PD-0332991
type
DRUG
arm Group Labels
PD-0332991 + Letrozole
description
Letrozole, 2.5mg, orally once daily (continuously)
name
Letrozole
type
DRUG
arm Group Labels
Placebo + Letrozole
description
Placebo, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment
name
Placebo
type
DRUG
arm Group Labels
Placebo + Letrozole
description
Letrozole, 2.5mg, orally once daily (continuously)
name
Letrozole
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: QUADRUPLE
who Masked: PARTICIPANT
CARE_PROVIDER
INVESTIGATOR
OUTCOMES_ASSESSOR

primary Purpose

TREATMENT

Enrollment

count: 666
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
PFS is defined as the time from the date of randomization to the date of the first documentation of objective tumor progression as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) or death due to any cause in the absence of documented PD, whichever occurs first. If tumor progression data include more than 1 date, the first date will be used. PFS (in months) will be calculated as (first event date - randomization date +1)/30.4. Progression is defined using RECIST v1.1, as a 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing non-target lesions, or the appearance of new lesions.
measure
Progression-Free Survival (PFS) as Assessed by the Investigator
time Frame
From randomization date to date of first documentation of progression or death (up to approximately 2.5 years)

secondary Outcomes

description
Objective Response (OR) defined as overall complete response (CR) or partial response (PR) according to RECIST v1.1. Objective Response Rate (ORR) is defined as proportion of participants with CR or PR relative to all randomized participants with measurable disease at baseline. Participants who do not have on-study radiographic tumor re-evaluation, who received anti-tumor treatment, or who died, progressed/ dropped out for any reason prior to reaching a CR or PR were counted as non-responders in assessment of ORR. Per RECIST v1.1, CR: Complete disappearance of target lesions with exception of nodal disease. All target nodes must decrease to normal size (short axis \<10mm). PR: \>=30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter is used in the sum for target nodes, while the longest diameter is used in the sum for all other target lesions. Stable Disease: neither sufficient shrinkage nor increase to qualify for disease progression.
measure
Objective Response as Assessed by the Investigator
time Frame
From randomization until end of treatment (up to approximately 2.5 years)
description
The OR is defined as the overall CR or PR according to the RECIST v1.1. ORR is defined as proportion of participants with CR or PR relative to all randomized participants with measurable disease at baseline. Participants who do not have on-study radiographic tumor re-evaluation, who received anti-tumor treatment, or who died, progressed/ dropped out for any reason prior to reaching a CR or PR were counted as non-responders in the assessment of ORR. Per RECIST v1.1, CR: Complete disappearance of target lesions with exception of nodal disease. All target nodes must decrease to normal size (short axis \<10mm). PR: \>=30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter is used in the sum for target nodes, while the longest diameter is used in the sum for all other target lesions. Stable Disease: neither sufficient shrinkage nor increase to qualify for disease progression.
measure
Objective Response: Participants With Measurable Disease at Baseline as Assessed by the Investigator
time Frame
From randomization until end of treatment (up to approximately 2.5 years)
description
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 will be used. DR was calculated as \[the date response ended (i.e. date of PD or death) - first CR or PR date + 1)\]/30.4. DR would only be calculated for the subgroup of participants with an objective tumor response. Per RECIST v1.1, CR: Complete disappearance of target lesions with exception of nodal disease. All target nodes must decrease to normal size (short axis \<10mm). PR: \>=30% decrease under baseline of the sum of diameters of all target measurable lesions.The short diameter is used in the sum for target nodes, while the longest diameter is used in the sum for all other target lesions. Stable Disease: neither sufficient shrinkage nor increase to qualify for disease progression.
measure
Duration of Response (DR)
time Frame
From randomization until end of treatment (up to approximately 2.5 years)
description
DC is defined as overall CR, PR, or stable disease (SD) \>=24 weeks according to RECIST version 1.1. Disease Control Rate (DCR) is defined as participants with CR, PR, or SD \>=24 weeks relative to all randomized participants. Participants who do not have on-study radiographic tumor reevaluation, who received anti-tumor treatment, a best response of SD\>=24 weeks, or who died, progressed, or dropped out for any reason prior to achieving reaching a CR or PR and a best response of SD\>=24 weeks was counted as non-responders in DCR. Per RECIST v1.1, CR: Complete disappearance of target lesions with exception of nodal disease. All target nodes must decrease to normal size (short axis \<10mm). PR: \>=30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter is used in the sum for target nodes, while the longest diameter is used in the sum for all other target lesions. SD: neither sufficient shrinkage nor increase to qualify for disease progression.
measure
Disease Control (DC)/Clinical Benefit Response (CBR)
time Frame
From randomization until end of treatment (up to approximately 2.5 years)
description
PFS by biomarker status by Investigator assessment. Progression is defined using RECIST v1.1, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Positive is defined as H-Score \>=1 and negative as H-Score \<1. H-Score is calculated as the sum of the % of cells at each level of staining intensity (0, 1+, 2+, and 3+) multiplied by the staining intensity value: H-Score = (% at 0)\*0 + (% at 1+)\*1 + (% at 2+)\*2 + (% at 3+)\*3. H-Score values range from 0 to 300. ER stands for estrogen receptor and Rb stands for retinoblastoma susceptibility gene product.
measure
PFS by Tumor Tissue Biomarkers Status, Including Genes (eg, Copy Numbers of CCND1, CDKN2A), Proteins (eg, Ki67, pRb), and RNA Expression (eg, cdk4, cdk6)
time Frame
From randomization until end of treatment (up to approximately 24 Months)
description
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and sent to a central laboratory for blinded manual adjudication. The average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR), by Bazette's formula (QTcB = QT divided by square root of RR) and corrected QT interval according to study-specific criteria (QTcS). Time-matched change from baseline values were reported for QTc analysis population.
measure
Corrected QT Interval (QTc) Time-Matched Change From Baseline on Cycle 1 Day 14
time Frame
Time-matched triplicate ECGs were collected at 0 (predose), 2, 4, 6 and 8 hours on Day 0 and on Cycle1 Day14
description
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and sent to a central laboratory for blinded manual adjudication. The average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR), by Bazette's formula (QTcB = QT divided by square root of RR) and corrected QT interval according to study-specific criteria (QTcS). Percentage of participants with post-baseline maximum absolute values and maximum increase from baseline were summarized for the safety analysis population.
measure
Percentage of Participants With Corrected QT Interval (QTc)
time Frame
For safety monitoring triplicate ECGs were obtained at 0 hour (pre-dose) on Day 1 of Cycle 1, Day 14 of Cycles 1 and Cycle 2, then on Day 1 of Cycles 4, 7, and 10 (ECGs beyond Cycle 10 were performed as clinically indicated)
description
Summary of plasma palbociclib within-participant mean steady-state trough concentrations.
measure
Observed Plasma Trough Concentration (Ctrough) at Steady-State
time Frame
0 hour (predose) on Day 14 of cycles 1 and 2
description
The EuroQol EQ-5D is a 6-item instrument designed to assess health status in terms of a single index value or utility score. It contains 5 descriptors of current health state (mobility, self-care, usual activities, pain or discomfort, and anxiety or depression) with each dimension having 3 levels of function (1=no problem, 2=some problem, and 3=extreme problem). The scores on the 5 descriptors are summarized to create a single summary score. An overall utility score is calculated based on these domains, with a range score from 0 (worse health scenario) to a maximum of 1.0 (best health scenario).
measure
Change From Baseline Between Treatment Comparison in Euro Quality of Life (EQ-5D) Index
time Frame
From Baseline up to 2.5 years
description
FACT is a modular approach to assess participant health-related quality of life using a 'core' set of questions (FACT-G) as well as a cancer site-specific module. The FACT-G is a 27-item compilation of general questions divided into 4 domains: Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, and Functional Well-Being. The FACT-B consisted of the FACT-G (27-item) and a breast-specific module: a 10-item instrument designed to assess participant concerns relating to breast cancer. For all questions, participants were asked to respond to a five-level scale where 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much. FACT-B total score = Physical Well-Being + Social/Family Well-Being + Emotional Well-Being + Functional Well-Being + Breast Cancer Subscale. As each of the items ranges from 0-4, the range of possible scores is 0-144, with 0 being the worst possible score and 144 the best.
measure
Change From Baseline Between Treatment Comparison in Functional Assessment of Cancer Therapy-Breast (FACT-B)
time Frame
From Baseline up to 2.5 years
description
An AE was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. SAE was any untoward medical occurrence at any dose that resulted in death; was life-threatening; required hospitalization; resulted in persistent or significant disability or in congenital anomaly/birth defect. TEAE were events that occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Severity was graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0 as Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening and Grade 5 = death related to AE. Discontinuation included permanent, temporary discontinuation and dose reduction due to AEs.
measure
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs): All Causalities
time Frame
From date of randomization up to 28 days after last dose of study drug (final analysis till study completion, approximately up to 10.51 years)
description
OS was defined as the time from date of randomization to date of death due to any cause. Participants without survival data beyond the date of their last follow-up were censored on the last date they were known to be alive. Data for this outcome measure was reported at primary analysis.
measure
Overall Survival (OS): Primary Analysis
time Frame
From date of randomization until death due to any cause or censored, (assessed up to data cut-off date of 15-Nov-2021, approximately 8.7 years)

Full study description

brief Summary: The study is designed to compare the clinical benefit following treatment with letrozole in combination with PD-0332991 versus letrozole in combination with placebo in postmenopausal women with ER(+)/HER2(-) advanced breast cancer who have not received prior systemic anti cancer therapies for their advanced/metastatic disease.

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