Hormone Receptor Positive Locally Advanced or Metastatic Breast Cancer MedDRA version: 9.1 Level: LLT Classification code 10027475 Term: Metastatic breast cancer
Conditions
Interventions
Product Name: AMG 479
Product Code: AMG 479
Pharmaceutical Form: Concentrate for solution for infusion
Current Sponsor code: AMG479
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type
Sponsors
Amgen Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
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. • 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 109/L - Platelet count = 100 x 109/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 or if total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 except the following is allowable: • Malignancy treated with curative intent and with no known active disease present for = 3 years before enrollment and felt to be at low risk for recurrence by the treating physician • Adequately treated non-melanomatous skin cancer or lentigo maligna without evidence of disease • Adequately treated cervical carcinoma in situ without evidence of disease 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 •
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To provide an estimate of the relative efficacy of Arm A (AMG 479 in combination with endocrine therapy [exemestane or fulvestrant] versus Arm B (AMG 479 placebo in combination with endocrine therapy [exemestane or fulvestrant]) as measured by the PFS hazard ratio. This estimate will be precise enough to provide guidance for further development of AMG 479.for use in the planning of a phase 3 study in this patient population. Additionally, this study will provide qualitative estimates of PFS for treatment arms A and B.;Secondary Objective: To investigate the effect of AMG 479 compared with placebo when administered in combination with exemestane or fulvestrant on: • the safety and tolerability • the impact to patient reported outcomes (PROs) • the pharmacokinetics (PK) of AMG 479 • additional efficacy measures including clinical benefit rate, objective response rate, duration of response, time to progression (TTP), time-to-response, time-to-treatment failure, and survival time;Primary end point(s): To provide an estimate of the relative efficacy of Arm A (AMG 479 in combination with endocrine therapy [exemestane or fulvestrant] versus Arm B (AMG 479 placebo in combination with endocrine therapy [exemestane or fulvestrant]) as measured by the PFS hazard ratio. This estimate will be precise enough to provide guidance for further development of AMG 479.for use in the planning of a phase 3 study in this patient population. Additionally, this study will provide qualitative estimates of PFS for treatment arms A and B. | — |
Countries
France, Germany, Ireland, Spain, United Kingdom
Outcome results
None listed