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

Advanced Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01137552
• Other study ID #: 20070879
• Status: Terminated
• Phase: Phase 1
• First received: April 22, 2010
• Last updated: March 2, 2015
• Start date: June 2010
• Est. completion date: April 2014

Study information

• Verified date: February 2015
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 44
• Est. completion date: April 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Solid Tumors

Intervention

Drug:
• AMG 780
AMG 780 will be administered by IV infusion every 2 weeks

Locations

Country	Name	City	State
United States	Research Site	Cleveland	Ohio
United States	Research Site	Durham	North Carolina
United States	Research Site	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)		2.5 years	Yes
Primary	To evaluate the pharmacokinetic (PK) parameters of AMG 780 including, but not limited to Cmax, AUC, and accumulation ratio		2.5 years	No
Secondary	To evaluate tumor response using RECIST criteria (measured by CT/MRI)		2.5 years	No
Secondary	To evaluate changes in tumor volume (measured by volumetric CT/MRI)		2.5 years	No
Secondary	To evaluate changes in tumor vascularity and to estimate the relationship between dose/pharmacokinetics and vascular response (measured by DCE-MRI)		2.5 years	No
Secondary	To evaluate the incidence of anti-AMG 780 antibody formation		2.5 years	Yes

External Links

•   AmgenTrials clinical trials website