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

Phase 1

Terminated

• Conditions: Advanced Solid Tumors
• Interventions: Drug: AMG 780

• Registration Number: NCT01137552
• Lead Sponsor: Amgen

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-04-22
• Study Start: 2010-06
• Study First Submitted QC: 2010-06-03
• Study First Posted: 2010-06-04
• Primary Completion: 2013-12
• Study Completion: 2014-04
• Status Verified: 2015-02
• Last Update Submitted: 2015-03-02
• Last Update Posted: 2015-03-04

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 44

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

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
A	AMG 780	Dose Escalation
B	AMG 780	Dose Expansion

Primary Outcome Measures

Name	Time	Method
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
To evaluate the pharmacokinetic (PK) parameters of AMG 780 including, but not limited to Cmax, AUC, and accumulation ratio	2.5 years

Secondary Outcome Measures

Name	Time	Method
To evaluate the incidence of anti-AMG 780 antibody formation	2.5 years
To evaluate changes in tumor vascularity and to estimate the relationship between dose/pharmacokinetics and vascular response (measured by DCE-MRI)	2.5 years
To evaluate tumor response using RECIST criteria (measured by CT/MRI)	2.5 years
To evaluate changes in tumor volume (measured by volumetric CT/MRI)	2.5 years

Trial Locations

Locations (1)

Research Site; 🇺🇸 Cleveland, Ohio, United States