A TWO-ARM RANDOMIZED OPEN LABEL PHASE 2 STUDY OF CP-751,871 IN COMBINATION WITH EXEMESTANE VERSUS EXEMESTANE ALONE AS FIRST LINE TREATMENT FOR POSTMENOPAUSAL PATIENTS WITH HORMONE RECEPTOR POSITIVE ADVANCED BREAST CANCER
- Conditions
- Hormone receptor positive advanced breast cancer in postmenopausal women.MedDRA version: 9.1Level: LLTClassification code 10057654Term: Breast cancer female
- Registration Number
- EUCTR2006-005573-21-GB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 250
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the study, unless there is compelling reason which is to be agreed by the investigator and sponsor prior to randomization:
1. Females >18 years of age.
2. Histologically or cytologically confirmed adenocarcinoma of the breast, either
metastatic, or locally advanced Stage IIIB, or loco-regional recurrent and not amenable to curative treatment with surgery or radiotherapy.
3. Measurable or evaluable disease.
4. Patients must be postmenopausal. Postmenopausal is defined by any of the
following:
• Woman = / > 60 yrs;
• Amenorrhea for = / >5 years prior to randomization;
• Woman of age 45-59 yrs with spontaneous amenorrhea for >1 year prior to randomization;
• Woman of age 45-59 yrs with cessation of menses duration <1 year or secondary
to hysterectomy AND with FSH levels pre-randomization clearly in the laboratory
postmenopausal range (or >34.4 IU/L if institutional range is not available);
• Woman of age 45-59 yrs previously on HRT who discontinued HRT at breast
cancer diagnosis and who has FSH level pre-chemotherapy or pre-randomization
clearly in the laboratory postmenopausal range (or >34.4 IU/L if institutional
range is not available);
• Bilateral oophorectomy;
• Ovarian ablation by radiotherapy confirmed by FSH level in the postmenopausal
range.
5. Evidence of hormone sensitivity (ER+ and/or PR+) of primary or secondary tumor
tissue according to the criteria of the participating Institution.
6. Must be appropriate to receive endocrine therapy as treatment for advanced disease.
7. Prior palliative radiotherapy is allowed. A measurable or evaluable lesion that has
been previously irradiated will be evaluated only after it is considered to have
progressed before randomization. Patients must have recovered from all acute
radiation toxicities.
8. Patients must have HbA1c<5.7%.
9. Concurrent bisphosphonate treatment is allowed but not required. Patients on
bisphosphonates at randomization must be kept on bisphosphonate during the study.
10. Patients must have an ECOG performance status 0, 1, or 2 ).
11. Adequate recovery from major surgery prior to randomization. Wound healing must be complete.
12. Patients must have adequate hematologic function as defined by:
• ANC = / >1500/mm3;
• Platelets = / >100000/mm3;
• Hemoglobin = / >8.5 g/Dl.
13. Patients must have adequate renal and liver function as defined by:
• Serum creatinine and serum bilirubin level < / =1.5 x ULN;
• ALT and AST < / = 2.5 x ULN (or =5 in case of liver metastasis).
14. Serum calcium < / = 11.6 mg/dL (or < / = 2.75 mmol/L).
15. Written and voluntary informed consent understood, signed and dated.
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
Patients presenting with any of the following will not be included in the study, unless there is compelling reason which is to be agreed by the investigator and sponsor prior to randomization:
1. Male patients.
2. Presence of life threatening metastatic disease defined as extensive (more than one third of the organ) hepatic involvement, any past or present brain or leptomeningeal involvement, or symptomatic pulmonary lymphangitic spread (>50% lung involvement). Patients with discrete pulmonary parenchymal metastases will not be excluded as long as their respiratory function is not compromised.
3. Presence of unevaluated central nervous system (CNS) symptoms suggestive of brain metastases within 2 weeks prior to randomization. CNS symptoms must be evaluated by CT or MRI scan.
4. Patients who are highly symptomatic from their breast cancer, or who require urgent palliative chemotherapy, as decided by their treating physician.
5. Adjuvant/neoadjuvant therapy with steroidal aromatase inhibitors within 12 months of randomization.
6. Adjuvant/neoadjuvant tamoxifen within 2 weeks of randomization.
Adjuvant/neoadjuvant chemotherapy (excluding anthracycline) within 4 weeks of
randomization.
8. Adjuvant/neoadjuvant anthracycline and/or trastuzumab therapy within 6 months of randomization.
9. Prior anti-IGF-1R investigational therapy.
10. Prior therapy for metastatic/advanced disease including, but not limited to,
chemotherapy, hormonal (eg, tamoxifen, SERMs, LHRH agonists, ovariectomy,
radiocastration) or targeted therapy, including immunotherapy. Prior AI is allowed if
less than 4 weeks prior to randomization.
11. Patients with a known hypersensitivity to exemestane or to any of its excipients.
12. Patients with a known hypersensitivity to antibody therapy.
13. History of malignancy other than breast cancer within 5 years before study start with the exception of appropriately treated cervical carcinoma in situ, basal cell carcinoma, or squamous cell carcinoma of the skin.
14. A serious uncontrolled medical disorder or active infection that would impair the
ability to receive study treatment.
15. Any history of unstable angina, myocardial infarction or symptomatic congestive
heart failure. Significant active cardiac disease including: uncontrolled high blood pressure (ie, systolic blood pressure =180 mm Hg, diastolic blood pressure =95 mm Hg), deep venous thrombosis, pulmonary embolism, endocarditis, cerebro-vascular attack, or valvular disease within the previous 6 months. Patients with a requirement for inotropic support or serious uncontrolled cardiac arrhythmia (including atrial flutter/fibrillation) within 3 years prior to screening. Patients requiring the use of pacemakers or implanted defibrillators.
16. Use of high dose corticosteroids within 2 weeks prior to randomization
(=100 mg prednisone per day or = / > 40 mg dexamethasone per day).
17. Dementia or significantly altered mental status that would limit the understanding or rendering of informed consent and compliance with the requirements of this protocol.
18. Any other major illnesses or laboratory abnormality that, in the Investigator’s
judgment, will substantially increase the risk associated with the patient’s participation in the 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