To Evaluate the Safety, Tolerability and Pharmacokinetics of AMG 386 When Used in Combination With AMG 706, Bevacizumab, Sorafenib, or Sunitinib.
February 7, 2017 updated by: Amgen
An Open-Label, Dose Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of AMG 386 With AMG 706, AMG 386 With Bevacizumab, AMG 386 With Sorafenib, and AMG 386 With Sunitinib in Adult Patients With Advanced Solid Tumors
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Anticipated)
88
Phase
- Phase 1
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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/exclusion criteria with the exception of alopecia.
- Active infection within 2 weeks before enrollment.
- Subject known to have tested positive for HIV.
- Subject known to have chronic hepatitis (e.g., hepatitis B or hepatitis C).
- Coumarin anticoagulants including warfarin, at doses greater than 2 mg/day. The concurrent use of low molecular weight heparin or low dose warfarin (ie, ≤ 2 mg daily for prophylaxis against central venous catheter thrombosis is acceptable.
- Treatment with anti-cancer therapy within 30 days before study day 1 (treatment with bevacizumab within 42 days before study day 1) unless prior written approval is received from the sponsor
- Hormonal anti-tumor therapy within 30 days before enrollment. Does not include hormones for non-cancer related conditions (eg, insulin for diabetes, HRT) or the use of gonadotropin-releasing hormone (GnRH) agonists for prostate cancer
- Therapeutic or palliative radiation therapy within 2 weeks before enrollment
- Prior treatment with AMG 386
- Prior radiation therapy to the abdomen
- For arms A, B, C, and D: prior treatment with bevacizumab, sorafenib, sunitinib, or investigational agents known to directly inhibit the functions of vascular endothelial growth factor, vascular endothelial growth factor receptors, angiopoietins, or angiopoietin receptors, unless prior written approval is received from the sponsor
- For arms E and F: prior treatment with sorafenib, unless prior written approval is received from the sponsor
- For arms G and H: prior treatment with sunitinib, unless prior written approval is received from the sponsor
- For arms E & F and G & H: treatment with bevacizumab within 42 days before study day 1, unless prior written approval is received from the sponsor
- Major surgery within 30 days before enrollment or recovering from prior surgery
- Subject who is pregnant or nursing
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
EXPERIMENTAL: D
3 mg/kg AMG 386 IV (QW) / 125 mg AMG 706 PO (QD)
|
AMG 706 125 mg PO (QD)
Other Names:
AMG 706 75 mg PO (QD)
Other Names:
AMG 386 10 mg/kg IV (QW)
AMG 386 3 mg/kg IV (QW)
|
|
EXPERIMENTAL: A
3 mg/kg AMG 386 IV (QW) / 15 mg/kg bevacizumab IV (Q3W)
|
AMG 386 10 mg/kg IV (QW)
AMG 386 3 mg/kg IV (QW)
Bevacizumab 15mg/kg IV Q3W
Other Names:
|
|
EXPERIMENTAL: B
3 mg/kg AMG 386 IV (QW) / 75 mg AMG 706 PO (QD)
|
AMG 706 125 mg PO (QD)
Other Names:
AMG 706 75 mg PO (QD)
Other Names:
AMG 386 10 mg/kg IV (QW)
AMG 386 3 mg/kg IV (QW)
|
|
EXPERIMENTAL: E
3 mg/kg AMG 386 IV (QW) / 400 mg sorafenib PO (BID)
|
AMG 386 10 mg/kg IV (QW)
AMG 386 3 mg/kg IV (QW)
Sorafenib 400 mg PO (BID)
Other Names:
|
|
EXPERIMENTAL: H
10 mg/kg AMG 386 IV (QW) / 50 mg sunitinib PO (QD - 4 weeks on/2 weeks off)
|
AMG 386 10 mg/kg IV (QW)
AMG 386 3 mg/kg IV (QW)
Sunitinib 50 mg PO (QD)
Other Names:
|
|
EXPERIMENTAL: G
3 mg/kg AMG 386 IV (QW) / 50 mg sunitinib PO (QD - 4 weeks on/2 weeks off)
|
AMG 386 10 mg/kg IV (QW)
AMG 386 3 mg/kg IV (QW)
Sunitinib 50 mg PO (QD)
Other Names:
|
|
EXPERIMENTAL: C
10 mg/kg AMG 386 IV (QW) / 15 mg/kg bevacizumab IV (Q3W)
|
AMG 386 10 mg/kg IV (QW)
AMG 386 3 mg/kg IV (QW)
Bevacizumab 15mg/kg IV Q3W
Other Names:
|
|
EXPERIMENTAL: F
10 mg/kg AMG 386 IV (QW) / 400 mg sorafenib PO (BID)
|
AMG 386 10 mg/kg IV (QW)
AMG 386 3 mg/kg IV (QW)
Sorafenib 400 mg PO (BID)
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
|---|
|
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 Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Response based on biomarker, anti-AMG 386 antibody formation and tumor response measure by RECIST.
Time Frame: End of Study
|
End of Study
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
December 1, 2005
Study Registration Dates
First Submitted
March 12, 2009
First Submitted That Met QC Criteria
March 12, 2009
First Posted (ESTIMATE)
March 13, 2009
Study Record Updates
Last Update Posted (ESTIMATE)
February 8, 2017
Last Update Submitted That Met QC Criteria
February 7, 2017
Last Verified
February 1, 2017
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Micronutrients
- Protein Kinase Inhibitors
- Vitamins
- Vitamin B Complex
- Sorafenib
- Sunitinib
- Bevacizumab
- Niacinamide
- Trebananib
- Imetelstat
- Motesanib diphosphate
Other Study ID Numbers
- 20050170
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.