PHASE 1/2, OPEN-LABEL, RANDOMIZED STUDY OF THE SAFETY, EFFICACY,AND PHARMACOKINETICS OF LETROZOLE PLUS PD 0332991 (ORAL CDK 4/6INHIBITOR) AND LETROZOLE SINGLE AGENT FOR THE FIRST-LINETREATMENT OF ER POSITIVE, HER2 NEGATIVE ADVANCED BREASTCANCER IN POSTMENOPAUSAL WOMEN - n/a
- Conditions
- Advanced Breast CancerMedDRA version: 9.1Level: LLTClassification code 10027475Term: Metastatic breast cancer
- Registration Number
- EUCTR2008-002392-27-FR
- 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 FSH and estradiol in the postmenopausal ranges
8. Eastern Cooperative Oncology Group (ECOG) Performance status 0 or 1 (see Appendix 1 of protocol).
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/µL
• Platelets = 100,000/µL
• Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) = 3 x upper limit of normal (ULN), or AST and ALT = 5 x ULN if liver function abnormalities are due to underlying malignancy
• Total serum bilirubin = 1.5 x ULN 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 = 470 msec
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 of protocol)
• (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.
5. Diagnosis of any secondary malignancy within the last 3 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix
6. Any of the following in the previous 6 months: 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.
7. Active inflammatory bowel disease or chronic diarrhea. Short bowel syndrome. Upper gastrointestinal surgery including gastric resection.
8. Known hypersensitivity to letrozole or to any of its excipients
9. Known human immunodeficiency virus infection
10. Other severe acute or chronic medical or psychiatric condition 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 subject inappropriate for entry into this study.
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