PHASE 1/2, OPEN-LABEL, RANDOMIZED STUDY OF THE SAFETY, EFFICACY, AND PHARMACOKINETICS OF LETROZOLE PLUS PD 0332991 (ORAL CDK 4/6 INHIBITOR) AND LETROZOLE SINGLE AGENT FOR THE FIRST-LINE TREATMENT OF ER POSITIVE, HER2 NEGATIVE ADVANCED BREAST CANCER IN POSTMENOPAUSAL WOMEN - A5481003
- Conditions
- Advanced Breast CancerMedDRA version: 12.0Level: LLTClassification code 10006178Term: Breast adenocarcinoma stage IV
- Registration Number
- EUCTR2008-002392-27-IT
- Lead Sponsor
- Pfizer Inc. 235 East 42nd Street New York NY 10017
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 150
1. Histologically or cytologically proven diagnosis of adenocarcinoma of the breast with evidence of 1) locally recurrent disease not amenable to resection or radiation therapy with curative intent, or 2) metastatic disease. 2 ER positive tumor. Positivity is defined either as ≥ 10 fmol of H3 -estrogen binding per mg of cytosol protein for dextran-coated charcoal and sucrose density methods, or ≥ 0.10 fmol of H3 -estrogen binding per mg of DNA for IF/EIA technique. In case of use of immunohistochemistry, the report should mention positive receptor status according to the standards of the laboratory. 3 HER2 negative breast cancer by FISH or IHC. 4 Paraffin-embedded tumor block(s) available for centralized assessment of Rb and other cell cycle-related proteins. 5 Measurable disease according to RECIST or bone-only disease. Previously irradiated lesions are deemed measurable only if progression is documented at the site after completion of radiation. 6 Females, 18 years of age or older 7 Postmenopausal status defined as:  Prior bilateral surgical oophorectomy;  Amenorrhea and age ≥ 60 years  Age < 60 years and amenorrhea for 12 or more months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression and in the postmenopausal ranges 8 Eastern Cooperative Oncology Group (ECOG) Performance status 0 or 1 (see Appendix 1). 9 Resolution of all acute toxic effects of prior therapy or surgical procedures to CTC grade ≤ 1 (except alopecia or other toxicities not considered a safety risk for the patient). 10 Adequate organ function as defined by the following criteria:  Absolute neutrophil count (ANC) ≥ 1500/?L  Platelets ≥ 100,000/?L  Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 3 x upper limit of normal (ULN), or AST and ALT ≤ 5 x UNL if liver function abnormalities are due to underlying malignancy  Total serum bilirubin ≤ 1.5 x UNL regardless of liver involvement secondary to tumor. Inclusion of patients with increased serum indirect bilirubin due to Gilbert?s syndrome is permitted.  Serum creatinine ≤ 1.5 x ULN ; QTc ≤ 470msec; 11 Signed and dated informed consent document indicating that the subject (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrollment. 12 Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1. Brain metastases (even if treated and stable), spinal cord compression, carcinomatous meningitis, or leptomeningeal disease. 2. Major surgery within 3 weeks of first study treatment. 3. Prior treatment with:  Any anti-cancer therapies for advanced disease, with the exception of radiation therapy to < 25% of bone marrow at least 2 weeks prior to study treatment initiation (see Appendix 2)  (neo)adjuvant letrozole; Any CDK inhibitor. 4. Current treatment with:  Any anti-cancer therapies for advanced disease  Any experimental treatment on another clinical trial  Therapeutic doses of anticoagulant. Low dose anticoagulants for deep vein thrombosis prophylaxis are allowed. Low molecular weight heparin is allowed. Aspirin is permitted.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the effect of letrozole plus PD 0332991 and of letrozole alone on progression-free survival (PFS) in the first line treatment of ER+, HER2 negative ABC ipostmenopausal womenn;Secondary Objective: To assess secondary measures of efficacy for PD 0332991 administered in combination;To assess the safety and tolerability of PD 0332991 administered in combination with letrozole and of letrozole alone;To assess the impact of PD 0332991 in combination with letrozole and of letrozole alone on patient reported outcomes of pain severity and pain interference with various activities of daily life using the Modified Brief Pain Inventory Sho To explore the relationship between the baseline tumor levels of Rb, p16/INK4A, CCND1, CDK4/6 and Ki67 markers and tumor response; To explore the relationship between germline polymorphism in CYP19A1 and CCND1 genes and tumor responsert Form (mBPI-sf) questionnaire;;Primary end point(s): Progression free survival
- Secondary Outcome Measures
Name Time Method