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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01942135
First received: September 10, 2013
Last updated: August 26, 2014
Last verified: August 2014
  Purpose

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).


Condition Intervention Phase
Metastatic Breast Cancer
Drug: Palbociclib
Drug: Fulvestrant
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)
Primary Purpose: Treatment
Official Title: Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial Of Fulvestrant (Faslodex®) 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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Progression-Free Survival [ Time Frame: Baseline up to approximately 10 months ] [ Designated as safety issue: No ]
    Time from randomization to the first documentation of objective tumor progression or to death due to any cause.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: Baseline until death (up to approximately 28 months) ] [ Designated as safety issue: No ]
    Time from randomization to date of death due to any cause.

  • Objective Response [ Time Frame: Baseline until approximately 10 months ] [ Designated as safety issue: No ]
    Complete or partial response recorded from randomization until disease progression or death due to any cause.

  • Duration of Response [ Time Frame: Baseline up to approximately 10 months ] [ Designated as safety issue: No ]
    Time from the first documentation of objective tumor response to objective tumor progression or death due to any cause.

  • Clinical Benefit Response (CBR) [ Time Frame: Baseline up to approximately 10 months ] [ Designated as safety issue: No ]
    CBR is defined as complete response or partial response or stable disease equal to or greater than 24 weeks according to RECIST version 1.1 recorded in the time period between randomization and disease progression or death of any cause.

  • 1 Year Probability of Participant Survival [ Time Frame: From baseline through 1 year ] [ Designated as safety issue: No ]
    Probability of survival one year after randomization.

  • 2 Year Probability of Participant Survival [ Time Frame: From baseline through 2 years ] [ Designated as safety issue: No ]
    Probability of survival 2 years after randomization

  • 3 Year Probability of Participant Survival [ Time Frame: From baseline through 3 years ] [ Designated as safety issue: Yes ]
    Probability of survival 3 years after randomization.

  • Minimum Observed Plasma Trough Concentration (Cmin) [ Time Frame: Cycles 1 and 2 ] [ Designated as safety issue: No ]
    Cmin for palbociclib, fulvestrant and goserelin (if applicable)

  • Alterations in genes, proteins, and ribonucleic acids relevant to the cell cycle, drug targets, tumor sensitivity and/or resistance [ Time Frame: From baseline until approximately 10 months ] [ Designated as safety issue: No ]
    Biomarkers from tissue including genes, proteins, and RNA expression

  • Euro Quality of Life (EQ-5D)- Health State Profile Utility Score [ Time Frame: From baseline through approximately month 10 ] [ Designated as safety issue: No ]
    EQ 5D (version 3L) is a 6 item instrument designed to assess health status in terms of a single index value or utility score.

  • European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) [ Time Frame: From baseline through approximately month 10 ] [ Designated as safety issue: No ]
    The EORTC QLQ C30 is a 30 item questionnaire composed of functional subscales; symptom scales; and other cancer related symptoms.

  • European Organization for Research and Treatment of Cancer breast cancer module (EORTC QLQ BR23) [ Time Frame: From baseline through approximately month 10 ] [ Designated as safety issue: No ]
    EORTC QLQ BR23 is a 23 item breast cancer specific companion module to the EORTC QLQ C30.

  • Time to Deterioration (TTD) [ Time Frame: From baseline through approximately month 10 ] [ Designated as safety issue: No ]
    Time from randomization to the first documentation of objective tumor progression, death due to any cause, and/or reduction in quality of life

  • Minimally Important Difference Cut-Off [ Time Frame: From baseline through approximately month 10 ] [ Designated as safety issue: No ]
    Number of time points where the minimally importance difference in QoL is achieved


Estimated Enrollment: 417
Study Start Date: September 2013
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A
Given until objective progression, symptomatic deterioration, unacceptable toxicity, death, or withdrawal of consent, whichever occurs first.
Drug: Palbociclib
Palbociclib 125 mg/day orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle.
Drug: Fulvestrant
Fulvestrant 500 mg intramuscularly on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle.
Active Comparator: Arm B
Given until objective progression, symptomatic deterioration, unacceptable toxicity, death, or withdrawal of consent, whichever occurs first.
Drug: Placebo
Placebo orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle.
Drug: Fulvestrant
Fulvestrant 500 mg intramuscularly on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01942135

  Show 278 Study Locations
Sponsors and Collaborators
Pfizer
AstraZeneca
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01942135     History of Changes
Other Study ID Numbers: A5481023
Study First Received: September 10, 2013
Last Updated: August 26, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Palbociclib (PD-0332991)
Fulvestrant
Goserelin
Hormone receptor-+
HER2-negative
Prior Endocrine treatment
any menopausal status
PALOMA-3

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Hormones
Estradiol
Fulvestrant
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Estrogens

ClinicalTrials.gov processed this record on August 27, 2014