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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01137552
First received: April 22, 2010
Last updated: April 17, 2014
Last verified: April 2014
  Purpose

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 Intervention Phase
Advanced Solid Tumors
Drug: AMG 780
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • To evaluate the pharmacokinetic (PK) parameters of AMG 780 including, but not limited to Cmax, AUC, and accumulation ratio [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate tumor response using RECIST criteria (measured by CT/MRI) [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]
  • To evaluate changes in tumor volume (measured by volumetric CT/MRI) [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • To evaluate the incidence of anti-AMG 780 antibody formation [ Time Frame: 2.5 years ] [ Designated as safety issue: Yes ]

Enrollment: 44
Study Start Date: June 2010
Study Completion Date: April 2014
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

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

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
  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: NCT01137552

Locations
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
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01137552     History of Changes
Other Study ID Numbers: 20070879
Study First Received: April 22, 2010
Last Updated: April 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Amgen:
First-In-Human
Dose Escalation
Dose Expansion
Advance Solid Tumors
Anti-Angiopoietin
Advance Malignancy
Cancer
Oncology
Oncology Patients
Phase 1
Clinical Trial
Tumors
Solid Tumors
Angiogenesis Inhibitors

Additional relevant MeSH terms:
Neoplasms
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 23, 2014