Advanced Solid Tumors
Conditions
Keywords
AMG 386, AMG 706, Bevacizumab, Sorafenib, Angiogenesis Inhibitors, Combination Therapy, Peptibody, Sunitinib
Brief summary
The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of AMG 386 when used in combination with AMG 706, bevacizumab, sorafenib, or sunitinib and that at least one dose level from each combination will be safe and well tolerated. AMG 386 is a man-made medication that is designed to stop the development of blood vessels in cancer tissues. Cancer tissues rely on the development of new blood vessels, a process called angiogenesis, to obtain a supply of oxygen and nutrients to grow.
Interventions
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men or women at least 18 years old. * Subjects must have a pathologically documented, and definitively diagnosed, advanced solid tumor that is refractory to standard treatment, for which no standard therapy is available, or for subjects who refuse standard therapy. * Subjects enrolling in arms E & F and G & H must have pathologically documented and definitively diagnosed advanced renal cell carcinoma. * Measurable disease or evaluable (non-measurable) disease per Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. * Eastern Cooperative Oncology Group (ECOG) performance status up to 2. * Subjects must be able to self-administer AMG 706 (arms B and D) or sorafenib (arms E and F) on an empty stomach (fasting for 1 hour before and 1 hour postdose) once daily for AMG 706 or twice daily for sorafenib. Subjects enrolling in arms G and H must be able to self-administer sunitinib once daily.
Exclusion criteria
* History of lymphoma or leukemia. * Symptomatic or untreated central nervous system metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation, and corticosteroids. * Subjects with head and neck cancer. * Subjects with lung squamous cell tumors or with large central (located adjacent to or within the hilum or mediastinum) tumor lesions ≥ 3 centimeters, regardless of histology * For arms A and C: Subjects with ovarian cancer. * History of arterial or venous thrombosis or pulmonary embolism within 1 year before enrollment; history of bleeding diathesis. * Cardiovascular events within 1 year before enrollment, such as myocardial infarction, unstable/severe angina, coronary/peripheral artery bypass graft, unstable cardiac arrhythmia requiring medication, symptomatic congestive heart failure (New York Heart Association \>class II), cerebrovascular accident or transient ischemic attack. * For arms G and H: LVEF ≤ 45%, heart rate \< 50 / min. * Chronic uncontrolled hypertension \[diastolic \> 85 mmHg; systolic \>145 mmHg\]. * History of pulmonary hemorrhage or gross hemoptysis within 6 months before enrollment. * History of significant GI surgery or disease, which would impair absorption. * Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Events (CTCAE) grade 0 or 1, or to levels dictated in the inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety including adverse events, clinically significant changes in laboratory results, ECG, and vital signs, to be measured throughout the study. Pharmacokinetic Profile of AMG 386 - blood levels of AMG 386 to be measured throughout the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Response based on biomarker, anti-AMG 386 antibody formation and tumor response measure by RECIST. | End of Study |
Outcome results
None listed