Status:
WITHDRAWN
Trastuzumab in Combination With AMG 479 in HER-2 Overexpressing MBC Progressing on Trastuzumab
Lead Sponsor:
M.D. Anderson Cancer Center
Collaborating Sponsors:
Amgen
Conditions:
Breast Cancer
Eligibility:
FEMALE
18+ years
Phase:
PHASE1
PHASE2
Brief Summary
The goal of Phase 1 of this clinical research study is to test the safety and tolerability of AMG 479 when given with trastuzumab. The goal of Phase 2 of this clinical research study is to learn if t...
Detailed Description
Phase 1 and Phase 2 of the Study: If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Groups of 3 participants will be...
Eligibility Criteria
Inclusion
- History of biopsy-proven HER-2-overexpressing breast cancer and radiographic evidence of metastatic disease. The HER-2 status can be determined either by immunohistochemistry (score, 3+) or by fluorescence in situ hybridization.
- Patients must have received anthracycline-, taxane- and capecitabine-based chemotherapy for breast cancer. In addition, patients must have developed progressive disease to trastuzumab- or lapatinib-based therapy within the last 3 months. Patients who develop metastatic breast cancer within 3 months after receiving trastuzumab or lapatinib in the adjuvant and/or neoadjuvant setting are eligible. Three prior lines of HER2-directed therapy (containing either trastuzumab or lapatinib) for metastatic breast cancer are allowed.
- Woman \>/=18 years old.
- Performance status 0-2 (by Eastern Cooperative Oncology Group {ECOG} scale).
- Laboratory parameters: Absolute neutrophil count (ANC) 1.0 x 10\^9/L or higher; Platelet count 100,000 x 10\^9/L or higher; Hemoglobin 9.0 g/dL or higher; Partial thromboplastin (PTT) \</= 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 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 registration(prior to the start of therapy). Continued in inclusion #6.
- Continuation from # 5: Serum creatinine \</= 1.5 x the ULN or calculated creatinine clearance (by Cockcroft-Gault formula) \>/=40 mL/min; 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.
- Glycosylated hemoglobin (HgbA1c)\</= 8%
- Fasting blood glucose \</= 160 mg/dL (Fasting will require subjects to refrain from all food and beverage \[except water\] for at least 8 hours). Documentation will confirm patient compliance with nothing by mouth (NPO) status prior to lab exam.
- Patients must not be pregnant. A pregnancy test will be obtained if the patient is a woman of child-bearing potential, defined as a sexually mature woman who has not undergone a hysterectomy or who has not been naturally postmenopausal for at least 24 consecutive months (i.e., who has had menses at any time in the preceding 24 consecutive months).
- Patients must have signed an informed consent document stating that they understand the investigational nature of the proposed treatment.
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>/= 20 mm with conventional techniques, including palpation, plain x-ray, or magnetic resonance imaging (MRI), or or \>/= 10 mm with spiral computed tomography (CT) scan. Bone metastases and pleural effusions are not considered measurable disease.
- Patients may not be receiving any other investigational agents within 30 days of registration.
- Left ventricular ejection fraction determined by echocardiogram or multiple-gated acquisition scan (MUGA) (cardiac scan) must be 50% or higher.
Exclusion
- Central nervous system (CNS) metastases , unless previously treated by either radiation therapy and/or surgical resection, clinically stable and off corticosteroids. Subjects with a history of CNS metastases that are both treated and stably controlled are eligible if all of the following apply: therapy has been administered (surgery and/or radiation therapy); there is no additional treatment planned for brain metastases; the subject is clinically stable; the subject is off corticosteroids or on a stable dose of corticosteroids for at least 14 days prior to enrollment
- 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 or longer.
- Administration of other prior anticancer therapies within 4 weeks of enrollment, except Trastuzumab and Lapatinib.
- Toxicities related to prior anticancer treatment (except alopecia) that have not resolved to \</= grade 1 according to common terminology criteria for adverse events (CTCAE V4.0) before registration or prior to start of therapy.
- 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.
- 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 registration (prior to the start of therapy).
- Minor surgical procedures within 7 days of registration although placement of central access device, fine needle aspiration, thoracentesis or paracentesis \> 1 day before registration is acceptable.
- Known inability to tolerate intravenous (IV) drug administration.
- Has not yet completed at least 30 days before registration since ending other investigational device or drug study(s)
- Subject has known sensitivity to any of the products to be administered during dosing.
- 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.
- Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- History of venous thromboembolism.
- Patient with reproductive potential who will not agree to use one highly effective method of contraceptive such as implants, injectables, intrauterine devices (IUDs) such as copper T or Levonorgestrel-releasing intrauterine system (LNG-IUS), sexual abstinence, vasectomised partner, or condom or occlusive cap (diaphragm or cervical/vault cap) supplemented with the use of a spermicide during treatment.
- Poorly controlled diabetes mellitus
- Patient with hearing impairment of \> grade 3.
Key Trial Info
Start Date :
November 1 2012
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
Estimated Enrollment :
Patients enrolled
Trial Details
Trial ID
NCT01479179
Start Date
November 1 2012
Last Update
October 26 2016
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