A Phase 1 Dose Escalation Study of AMG 780 in Adult Subjects With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01137552
Recruitment Status : Terminated (Part A, the dose escalation and primary objective of the study, was completed. Part B, the dose expansion, was not conducted due to a business decision.)
First Posted : June 4, 2010
Last Update Posted : March 4, 2015
Information provided by (Responsible Party):

Brief Summary:
This is a first in human, open-label, sequential dose escalation and expansion study of AMG 780 in up to 62 subjects with advanced solid tumors. The dose escalation part of the study is aimed at evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of AMG 780. The dose expansion will consist of up to 20 subjects and the dose level of AMG 780 will be dependent upon emerging safety and PK data from the dose escalation part of the study.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Drug: AMG 780 Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, First-in-Human Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AMG 780 in Adult Subjects With Advanced Solid Tumors
Study Start Date : June 2010
Actual Primary Completion Date : December 2013
Actual Study Completion Date : April 2014

Arm Intervention/treatment
Experimental: A
Dose Escalation
Drug: AMG 780
AMG 780 will be administered by IV infusion every 2 weeks
Experimental: B
Dose Expansion
Drug: AMG 780
AMG 780 will be administered by IV infusion every 2 weeks

Primary Outcome Measures :
  1. To assess the safety and tolerability of AMG 780 in subjects with advanced solid malignancies (including adverse event rate, incidence of dose-limiting toxicities, and determination of maximum tolerated dose) [ Time Frame: 2.5 years ]
  2. To evaluate the pharmacokinetic (PK) parameters of AMG 780 including, but not limited to Cmax, AUC, and accumulation ratio [ Time Frame: 2.5 years ]

Secondary Outcome Measures :
  1. To evaluate tumor response using RECIST criteria (measured by CT/MRI) [ Time Frame: 2.5 years ]
  2. To evaluate changes in tumor volume (measured by volumetric CT/MRI) [ Time Frame: 2.5 years ]
  3. To evaluate changes in tumor vascularity and to estimate the relationship between dose/pharmacokinetics and vascular response (measured by DCE-MRI) [ Time Frame: 2.5 years ]
  4. To evaluate the incidence of anti-AMG 780 antibody formation [ Time Frame: 2.5 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Men and women ≥ 18 years old
  • Must have a pathologically documented, and definitely diagnosed, advanced solid tumor that is refractory to standard treatment, or for which no curative therapy is available, or for subjects who refuse standard therapy
  • Measurable disease by RECIST criteria
  • Must be able to undergo MRI evaluation
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Competent to sign and date an Institutional Review Board approved informed consent form

Exclusion Criteria:

  • Presence of untreated or symptomatic primary central nervous system tumors or metastases
  • Presence of leukemia or myelodysplastic syndrome
  • Subjects with head and neck cancer
  • Previous hematopoietic stem cell transplant (allogeneic)
  • Unresolved hematological toxicities > grade 1 with the exception of grade 2 lymphopenia and non-hematological toxicities > grade 1, excluding alopecia and grade 2 neuropathy, from prior anti-cancer therapy
  • Myocardial infarction within 1 year before study day 1, or unstable or uncontrolled disease/condition related to or affecting cardiac function
  • History of stroke, arterial or venous thrombosis, or pulmonary embolism within 1 year before study
  • Active peripheral vascular disease
  • History of bleeding diathesis
  • History of pulmonary hemorrhage or gross hemoptysis within 6 months before study
  • Known history of adrenal hemorrhage
  • Known positive test for human immunodeficiency virus infection, or active hepatitis B or hepatitis C
  • Major surgery within 1 month before study
  • Prior treatment with any agent targeting the angiopoietin-Tie2 signaling pathway
  • Concurrent antitumor treatment, except Lupron for subjects with prostate cancer and selective estrogen receptor modulators (SERMS) for subjects with breast cancer, within 4 weeks (6 weeks for nitrosoureas or mitomycin) before study day 1
  • Known sensitivity to mammalian-derived products, bacterially-produced proteins, or any of the products to be administered during dosing
  • Investigational agent within 30 days before study
  • Pregnant (eg, positive urine test) or breastfeeding
  • Subjects of childbearing potential, or subject who has a partner of childbearing potential, and is not using highly effective contraceptive precautions

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01137552

United States, California
Research Site
Los Angeles, California, United States, 90048
United States, North Carolina
Research Site
Durham, North Carolina, United States, 27710
United States, Ohio
Research Site
Cleveland, Ohio, United States, 44106
Sponsors and Collaborators
Study Director: MD Amgen

Additional Information:
Responsible Party: Amgen Identifier: NCT01137552     History of Changes
Other Study ID Numbers: 20070879
First Posted: June 4, 2010    Key Record Dates
Last Update Posted: March 4, 2015
Last Verified: February 2015

Keywords provided by Amgen:
Dose Escalation
Dose Expansion
Advance Solid Tumors
Advance Malignancy
Oncology Patients
Phase 1
Clinical Trial
Solid Tumors
Angiogenesis Inhibitors

Additional relevant MeSH terms: