To Evaluate the Safety, Tolerability and Pharmacokinetics of AMG 386 When Used in Combination With AMG 706, Bevacizumab, Sorafenib, or Sunitinib.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00861419
First received: March 12, 2009
Last updated: March 29, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Advanced Solid Tumors
Drug: Sorafenib
Drug: AMG 706
Drug: AMG 386
Drug: Sunitinib
Drug: Bevacizumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • 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. [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Response based on biomarker, anti-AMG 386 antibody formation and tumor response measure by RECIST. [ Time Frame: End of Study ] [ Designated as safety issue: No ]

Estimated Enrollment: 88
Study Start Date: December 2005
Study Completion Date: September 2012
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: D
3 mg/kg AMG 386 IV (QW) / 125 mg AMG 706 PO (QD)
Drug: AMG 706
AMG 706 125 mg PO (QD)
Other Name: Motesanib Diphosphate
Drug: AMG 386
AMG 386 3 mg/kg IV (QW)
Experimental: A
3 mg/kg AMG 386 IV (QW) / 15 mg/kg bevacizumab IV (Q3W)
Drug: Bevacizumab
Bevacizumab 15mg/kg IV Q3W
Other Name: Avastin
Drug: AMG 386
AMG 386 3 mg/kg IV (QW)
Experimental: B
3 mg/kg AMG 386 IV (QW) / 75 mg AMG 706 PO (QD)
Drug: AMG 706
AMG 706 75 mg PO (QD)
Other Name: Motesanib Diphosphate
Drug: AMG 386
AMG 386 3 mg/kg IV (QW)
Experimental: E
3 mg/kg AMG 386 IV (QW) / 400 mg sorafenib PO (BID)
Drug: Sorafenib
Sorafenib 400 mg PO (BID)
Other Name: Nexavar
Drug: AMG 386
AMG 386 3 mg/kg IV (QW)
Experimental: H
10 mg/kg AMG 386 IV (QW) / 50 mg sunitinib PO (QD - 4 weeks on/2 weeks off)
Drug: AMG 386
AMG 386 10 mg/kg IV (QW)
Drug: Sunitinib
Sunitinib 50 mg PO (QD)
Other Name: Sutent
Experimental: G
3 mg/kg AMG 386 IV (QW) / 50 mg sunitinib PO (QD - 4 weeks on/2 weeks off)
Drug: Sunitinib
Sunitinib 50 mg PO (QD)
Other Name: Sutent
Drug: AMG 386
AMG 386 3 mg/kg IV (QW)
Experimental: C
10 mg/kg AMG 386 IV (QW) / 15 mg/kg bevacizumab IV (Q3W)
Drug: AMG 386
AMG 386 10 mg/kg IV (QW)
Drug: Bevacizumab
Bevacizumab 15mg/kg IV Q3W
Other Name: Avastin
Experimental: F
10 mg/kg AMG 386 IV (QW) / 400 mg sorafenib PO (BID)
Drug: Sorafenib
Sorafenib 400 mg PO (BID)
Other Name: Nexavar
Drug: AMG 386
AMG 386 10 mg/kg IV (QW)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00861419

Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00861419     History of Changes
Other Study ID Numbers: 20050170
Study First Received: March 12, 2009
Last Updated: March 29, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Amgen:
AMG 386
AMG 706
Bevacizumab
Sorafenib
Angiogenesis Inhibitors
Combination Therapy
Peptibody
Sunitinib

Additional relevant MeSH terms:
Bevacizumab
Sunitinib
Sorafenib
Niacinamide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients

ClinicalTrials.gov processed this record on October 01, 2014