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

Phase 3

Completed

Conditions: breast cancer
10006291

Registration Number: NL-OMON50735

Lead Sponsor: Pfizer

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 35

Inclusion Criteria

Women 18 years of age or older, who are either:, - Postmenopausal, as defined
by at least one of the following criteria:, - Age * 60 years;, - Age <60
years and cessation of regular menses for at least 12 consecutive months with
no alternative pathological or physiological cause; and serum estradiol and FSH
level within the laboratory*s reference range for postmenopausal females;, -
Documented bilateral oophorectomy;, - Medically confirmed ovarian failure., OR,
- Pre/peri-menopausal, ie, not meeting the criteria for being postmenopausal.,
- Pre/perimeopausal women can be enrolled if amenable to be treated with the
LHRH agonist goserelin. Patients must have commenced treatment with goserelin
or an alternative LHRH agonist at least 4 weeks prior to randomization. But, if
patients have received an alternative LHRH agonist prior to study entry, they
must switch to goserelin for the duration of the trial., 2. Histologically or
cytologically proven diagnosis of breast cancer with evidence of metastatic or
locally advanced disease, not amenable to resection or radiation therapy with
curative intent., 3. Documentation of ER-positive and/or PR-positive tumor (*1%
positive stained cells) based on most recent tumor biopsy (unless bone-only
disease, see below) utilizing an assay consistent with local standards., 4.
Documented HER2-negative tumor based on local testing on most recent tumor
biopsy: HER2-negative tumor is determined as immunohistochemistry score 0/1+ or
negative by in situ hybridization (FISH/CISH/SISH) defined as a HER2/CEP17
ratio <2 or for single probe assessment a HER2 copy number <4., 5.
Patients must satisfy the following criteria for prior therapy:, - Progressed
during treatment or within 12 months of completion of adjuvant therapy with an
aromatase inhibitor if postmenopausal, or tamoxifen if pre- or perimenopausal.,
OR, - Progressed while on or within 1 month after the end of prior aromatase
inhibitor therapy for advanced/metastatic breast cancer if postmenopausal, or
prior endocrine treatment for advanced/metastatic breast cancer if pre- or
perimenopausal., One previous line of chemotherapy for advanced/metastatic
disease is allowed in addition to endocrine therapy., 6. Except where
prohibited by local regulations, all patients must agree to provide and have
available a formalin-fixed paraffin embedded (FFPE) tissue biopsy sample taken
at the time of presentation with recurrent or metastatic disease. A de novo
biopsy is required, if no archived tissue is available taken at the time of
presentation with recurrent/metastatic. The sole exception is those patients
with bone, only disease for whom provision of previous archival tissue only is
acceptable. Patients, who had surgery within the last 3 years (but without
neoadjuvant chemotherapy prior to surgery) and relapsed while receiving
adjuvant therapy, may provide a tumor specimen from that surgery., 7.
Measurable disease as defined by RECIST version 1.1, or bone-only disease.
Patients with bone-only metastatic cancer must have a lytic or mixed
lytic-blastic lesion that can be accurately assessed by CT or MRI. Patients
with bone-only disease and blastic-only metastasis are not eligible. Tumor
lesions previously irradiated or subjected to other loco, regional therapy will
only be deemed measurable

Exclusion Criteria

1. Prior treatment with any CDK inhibitor, or fulvestrant, or with everolimus,
or any agent whose mechanism of action is to inhibit the PI3K-mTOR pathway., 2.
Patients with advanced/metastatic, symptomatic, visceral spread, that are at
risk of life-threatening complications in the short term (including patients
with massive uncontrolled effusions [pleural, pericardial, peritoneal],
pulmonary lymphangitis, and over 50% liver involvement)., 3. Known active
uncontrolled or symptomatic Central Nervous System (CNS) metastases,
carcinomatous meningitis, or leptomeningeal disease as indicated by clinical
symptoms, cerebral edema, and/or progressive growth. Patients with a history of
CNS metastases or cord compression are eligible if they have been definitively
treated (eg, radiotherapy,, stereotactic surgery) and are clinically stable off
anticonvulsants and steroids for at least 4 weeks before randomization., 4.
Current use of food or drugs known to be potent CYP3A4 inhibitors, drugs known
to be potent CYP3A4 inducers (for examples, see the Prohibited Medications
section), and drugs that are known to prolong the QT interval., 5. Major
surgery, chemotherapy, radiotherapy, or other anti cancer therapy within 2
weeks before randomization. Patients who received prior radiotherapy to * 25%
of bone marrow are not eligible independent of when it was received., 6. Any
other malignancy within 3 years prior to randomization, except for adequately
treated basal cell or squamous cell skin cancer, or carcinoma in situ of the
cervix., 7. QTc interval >480 msec (based on the mean value of the
triplicate ECGs), family or personal history of long or short QT syndrome,
Brugada syndrome or known history of QTc prolongation or Torsade de Pointes.,
8. Any of the following within 6 months of randomization: myocardial
infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE
Grade *2, atrial fibrillation of any grade, coronary/peripheral artery bypass
graft, symptomatic congestive heart failure, cerebrovascular accident including
transient ischemic attack, or symptomatic pulmonary embolism., 9. Impairment of
gastro-intestinal (GI) function or GI disease that may significantly alter the
absorption of palbociclib, such as history of GI surgery with may result in
intestinal blind loops and patients with clinically significant gastroparesis,
short bowel syndrome, unresolved nausea, vomiting, active inflammatory bowel
disease or diarrhea of CTCAE Grade >1., 10. Prior hematopoietic stem cell or
bone marrow transplantation., 11. Known abnormalities in coagulation such as
bleeding diathesis, or treatment with anticoagulants precluding intramuscular
injections of fulvestrant or goserelin (if applicable)., 12. Known or possible
hypersensitivity to fulvestrant, goserelin, any of their excipients or to any
palbociclib/placebo excipients., 13. Known human immunodeficiency virus
infection., 14. Other severe acute or chronic medical or psychiatric condition,
including recent or active suicidal ideation or behavior, or laboratory
abnormality that may increase the risk associated with study participation or
investigational product administration or may interfere with the interpretation
of study results and, in the judgment of the investigator, would make the
patient inappropriate for