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

Purpose

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.

Condition	Intervention	Phase
Breast Neoplasms	Drug: PD-0332991 Drug: Letrozole Drug: Placebo	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Randomized, Multicenter, Double-Blind Phase 3 Study Of PD-0332991 (Oral CDK 4/6 Inhibitor) Plus Letrozole Versus Placebo Plus Letrozole For The Treatment Of Postmenopausal Women With ER (+), HER2 (-) Breast Cancer Who Have Not Received Any Prior Systemic Anti Cancer Treatment For Advanced Disease

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Letrozole Palbociclib

U.S. FDA Resources

Further study details as provided by Pfizer:

Primary Outcome Measures:

Progression-Free Survival (PFS) [ Time Frame: Baseline up to 2.5 years ] [ Designated as safety issue: No ]
Median time from the first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.

Secondary Outcome Measures:

Probability of Participant Survival [ Time Frame: From start of study treatment up to 6 years ] [ Designated as safety issue: Yes ]
Probability of survival 1-year, 2- and 3-years after the first dose of study treatment
Overall Survival (OS) [ Time Frame: Baseline to date of death from any cause (up to 6 years) ] [ Designated as safety issue: Yes ]
Time from date of randomization to date of death due to any cause.
Objective Response (OR) [ Time Frame: Baseline up to 2.5 years ] [ Designated as safety issue: No ]
OR is defined as a complete response (CR) or partial response (PR) according to RECIST v.1.1. recorded from randomization until disease progression or death due to any cause.
Duration of Response (DR) [ Time Frame: Baseline up to 2.5 years ] [ Designated as safety issue: No ]
Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cancer.
Disease Control (DC) [ Time Frame: Baseline up to 2.5 years ] [ Designated as safety issue: No ]
DC is defined as complete response (CR), partial response (PR), or stable disease (SD) ≥24 weeks according to the RECIST version 1.1 recorded in the time period between randomization and disease progression or death to any cause.
QTc interval [ Time Frame: Baseline and Day 14 of Cycle 1 ] [ Designated as safety issue: Yes ]
Time between the start of the Q wave and the end of the T wave corrected for heart rate.
Minimum Observed Plasma Trough Concentration (Cmin) [ Time Frame: Day 14 of cycles 1 and 2 ] [ Designated as safety issue: No ]
Minimum Observed Plasma Trough Concentration (Cmin)
Change From Baseline in Euro Quality of Life (EQ-5D)- Health State Profile Utility at Week X [ Time Frame: Baseline up to 2.5 years ] [ Designated as safety issue: No ]
Instrument designed to assess health status in terms of a single index value or utility score.
Change From Baseline in Functional Assessment od Cancer therapy -Breast (FACT-B) at Week X [ Time Frame: Baseline up to 2.5 years ] [ Designated as safety issue: No ]
Instrument designed to assess patient concerns relating to breast cancer
Tumor tissue biomarkers [ Time Frame: Baseline, 24 months ] [ Designated as safety issue: No ]
Tumor tissue biomarkers will be analyzed to investigate possible associations with resistance/sensitivity to treatment with study drugs. Biomarkers that will be analyzed will be selected based on their known relevance to mechanisms involved in cell cycle regulation.


Estimated Enrollment:	650
Study Start Date:	February 2013
Estimated Study Completion Date:	November 2018
Primary Completion Date:	February 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: PD-0332991 + Letrozole 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).	Drug: PD-0332991 PD-0332991, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment Drug: Letrozole Letrozole, 2.5mg, orally once daily (continuously)
Active Comparator: Placebo + Letrozole 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).	Drug: Placebo Placebo, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment Drug: Letrozole Letrozole, 2.5mg, orally once daily (continuously)

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01740427

Show 320 Study Locations

Sponsors and Collaborators

Pfizer

Investigators


Study Director:	Pfizer CT.gov Call Center	Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. This link exits the ClinicalTrials.gov site


Responsible Party:	Pfizer
ClinicalTrials.gov Identifier:	NCT01740427 History of Changes
Other Study ID Numbers:	A5481008 2012-004601-27
Study First Received:	November 26, 2012
Last Updated:	July 13, 2016
Health Authority:	United States: Food and Drug Administration

Keywords provided by Pfizer:


breast cancer postmenopausal women estrogen-receptor positive HER2 negative	locoregionally recurrent metastatic Palbociclib (PD-0332991) PALOMA-2

Additional relevant MeSH terms:


Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Letrozole Palbociclib 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 Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on September 30, 2016