Estudio internacional, aleatorizado, a doble ciego, controlado con placebo y de fase 2 de AMG 479 con exemestano o fulvestrant en mujeres posmenopáusicas que presentan cáncer de mama localmente avanzado o metastásico con receptor hormonal positivo.An International, Randomized, Double-blind, Placebo-controlled, Phase 2 Study of AMG 479 with Exemestane or Fulvestrant in Postmenopausal Women with Hormone Receptor Positive Locally Advanced or Metastatic Breast Cancer

Conditions: Cáncer de mama localmente avanzado o metastásico con receptor hormonal positivoHormone Receptor Positive Locally Advanced or Metastatic Breast Cancer
MedDRA version: 9.1Level: LLTClassification code 10027475Term: Metastatic breast cancer

Registration Number: EUCTR2007-006050-25-ES

Lead Sponsor: Amgen Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Female

Target Recruitment: 150

Inclusion Criteria

Disease related
• Histologically or cytologically confirmed carcinoma of the breast with locally advanced or metastatic disease not amenable to surgery or radiation with curative intent (based on medical history review)
• Confirmation of hormone receptor (ER and/or progesterone receptor) positive disease using institutional standards for analysis of the primary tumor tissue or tissue obtained thereafter (based on medical history review)
• Amenable to receive endocrine therapy as per investigator discretion
• Disease progression while receiving prior endocrine therapy for locally advanced or metastatic breast cancer or recurrence while receiving prior endocrine therapy as adjuvant treatment or within 12 months of treatment discontinuation. Although, endocrine therapy must have been administered for at least 6 months before disease progression/recurrence occurred
• Measurable or non-measurable disease, as defined by RECIST criteria
• Eastern Cooperative Oncology Group (ECOG, refer to Appendix I) performance status of 0 or 1
• Documented life expectancy greater than 3 months

Demographic
• Woman = 18 years old
• Postmenopausal as defined by any of the following criteria:
- History of bilateral oophorectomy, or
- Age = 55 years old, or
- = 45 years old with amenorrhea for = 12 months, or
- = 45 years old with amenorrhea and follicle stimulating hormone concentrations within postmenopausal range, or
- Follicle stimulating hormone concentrations within postmenopausal range in patients previously treated with bilateral ovarian radiation, or patients with chemotherapy induced amenorrhea

Laboratory
• Hematological function, as follows:
- Absolute neutrophil count (ANC) = 1.0 x 10e9/L
- Platelet count = 100 x 10e9/L
- Hemoglobin = 9 g/dL
• Partial thromboplastin = 1.3 x upper limit of normal (ULN) and international normalized ratio (INR) = 1.5, unless subject is on anticoagulation therapy. Subjects on therapeutic anticoagulation are eligible if they will be prescribed exemestane as their endocrine therapy on the study, there is no bleeding and they are on a stable dose of anticoagulation therapy (eg, on coumadin with an INR of 2 to 3) for at least 7 days before randomization.
• Renal function, as follows:
- Serum creatinine = 1.5 x the ULN or calculated creatinine clearance (by Cockcroft-Gault formula) = 40 mL/min
• Hepatic function, as follows:
- Aspartate aminotransferase (AST) = 2.5 x ULN
- Alanine aminotransferase (ALT) = 2.5 x ULN
- Alkaline phosphatase = 2.5 x ULN (= 5 x ULN with bone/liver metastases)
- Bilirubin = 1.5 x ULN
• Adequate glycemic function, for subjects with known diabetes (Type 1 or 2), as
follows:
- Must be controlled with a glycosylated hemoglobin (HgbA1c) of < 8.0%
- Documented fasting blood sugars < 160 mg/dL. Diabetic subjects who have recently had their glycemic control regimens adjusted and have documented fasting blood glucose concentrations < 160 mg/dL may be considered, regardless of HgbA1c value, if per investigator discretion are considered to have adequate glycemic function
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

Exclusion Criteria

Disease Related
• HR-unknown, or -negative disease (based on medical history review)
• Not amenable to receive endocrine therapy, including but not limited to, inflammatory breast cancer, rapidly progressing disease, or symptomatic visceral
disease
• Central nervous system metastases, unless previously treated by either radiation therapy and/or surgical resection, who are clinically stable off corticosteroids before randomization
• Prior malignancy (other than in situ cervical cancer, or basal cell or squamous cell carcinoma of the skin), unless treated with curative intent and without evidence of disease for = 3 years

Medications
• More than 1 prior endocrine regimen for metastatic breast cancer, or locally advanced breast cancer. There are no restrictions for their administration in the neoadjuvant or adjuvant settings, except subjects should not have previously been treated with the endocrine therapy planned for use in this study
• More than 1 prior regimen including immunotherapy (eg, vaccines), antibody therapy (eg, trastuzumab, bevacizumab), small-molecule therapy (eg, lapatinib) for metastatic breast cancer, or locally advanced breast cancer, although there are no restrictions for their administration in the neoadjuvant or adjuvant settings
• More than 1 prior regimen including chemotherapy for metastatic breast cancer,
or locally advanced breast cancer, although there are no restrictions for their administration in the neoadjuvant or adjuvant settings
• For subjects with measurable disease, previous radiation therapy to a lesion being used for RECIST assessment, unless it has subsequently progressed after completion of therapy
• Administration of prior endocrine anticancer therapies within 1 week of randomization
• Administration of other prior anticancer therapies within 2 weeks of randomization
• Toxicities related to prior anticancer treatment (except alopecia) have not resolved to common terminology criteria for adverse events version 3.0 (CTCAE V 3.0) defined = grade 1 before randomization
• Prior treatment with investigational treatment targeted to IGF axis including, but not limited to, CP 751,871, IM-A12, RO4858696
• Previous exposure to AMG 479
• Currently receiving systemic antibiotic therapy for the treatment of an active infection
• Requirement for other endocrine therapy including:
- systemic hormone-replacement therapy or intravaginal estrogen
- megestrol acetate

General
• History of bleeding diathesis
• Known positive test for human immunodeficiency virus, or chronic hepatitis B or C infection
• Any co-morbid medical condition that may put the subject at significant risk for toxicity
• Major surgical procedure within 28 days of randomization
• Minor surgical procedures within 7 days of randomization, although placement of central access device, fine needle aspiration, thoracentesis or paracentesis > 1 day before randomization is acceptable
• Inability to tolerate IV drug administration
• Has not yet completed at least 30 days before randomization since ending other investigational device or drug study(s)
• Subject has known sensitivity to any of the products to be administered during dosing
• Subject previously randomized to this study
• Subject will not be available for follow-up assessments
• Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures
• Unable to initiation study treatment within 3 days of randomization