Palbociclib (PD-0332991) Combined With Fulvestrant In Hormone Receptor+ HER2-Negative Metastatic Breast Cancer After Endocrine Failure (PALOMA-3)
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Palbociclib; Fulvestrant; Placebo; Fulvestrant
Intervention description: Palbociclib 125 mg/day orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle.; Fulvestrant 500 mg intramuscularly on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle.; Placebo orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle.; Fulvestrant 500 mg intramuscularly on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle.
Intervention MeSH terms: Fulvestrant; Palbociclib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 521.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Palbociclib (PD-0332991); Fulvestrant; Goserelin; Hormone receptor-+; HER2-negative; Prior Endocrine treatment; any menopausal status; PALOMA-3

Summary:

      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).
    

Eligibility 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