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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01740427
First received: November 26, 2012
Last updated: August 26, 2014
Last verified: August 2014
  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:


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: October 2016
Estimated Primary Completion Date: October 2015 (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
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 273 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01740427     History of Changes
Other Study ID Numbers: A5481008
Study First Received: November 26, 2012
Last Updated: August 26, 2014
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
Neoplasms by Site
Breast Diseases
Skin Diseases
Letrozole
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014