A study investigating new drug PD-0332991 (PALBOCICLIB) for treatment of women with Hormone Receptor-Positive, Her2-Negative Metastatic Breast Cancer. Study has two groups: Allpatients will be treated with Fulvestrant (FASLODEX) and Goserelin (Zoladex). In addition, one group will receive PD-0332991 (PALBOCICLIB), the other group an inactive substance. Neither the patient northe doctor will know the treatment group. The distribution into the groups will be random.
- Conditions
- HORMONE RECEPTOR-POSITIVE, HER2-NEGATIVE METASTATIC BREAST CANCERMedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-002580-26-NL
- Lead Sponsor
- Pfizer Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 521
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 taken at the time of presentation with recurrent/metastatic disease
is available. 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 if progression at the treated site after completion of therapy is clearly documented.
8. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
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 entry into this study.
15. Patients who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method