A Study of AMG 820 in Subjects With Advanced Solid Tumors

Sponsor

Amgen (Industry)

Overall Status

Completed

CT.gov ID

NCT01444404

Collaborator

(none)

Enrollment

Locations

Arms

70.2

Actual Duration (Months)

8.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

First in human, open-label, sequential dose escalation and expansion study of AMG 820 in subjects with advanced solid tumors.

Condition or Disease	Intervention/Treatment	Phase
Advanced Malignancy Advanced Solid Tumors Cancer Oncology Oncology Patients Tumors	Drug: AMG 820	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

25 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 Pharmacokinetics of AMG 820 in Adult Subjects With Advanced Solid Tumors

Actual Study Start Date :

Mar 31, 2008

Actual Primary Completion Date :

Feb 6, 2014

Actual Study Completion Date :

Feb 6, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Expansion The dose expansion will consist of up to 20 subjects and the dose level of AMG 820 will be dependent upon emerging safety and PK data from the dose escalation part of the study.	Drug: AMG 820 AMG 820 is a fully human IgG2 c-fms antagonistic antibody and will be given every two weeks until progression or unacceptable toxicity develops.
Experimental: Dose Escalation The dose escalation part of the study is aimed at evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of AMG 820.	Drug: AMG 820 AMG 820 is a fully human IgG2 c-fms antagonistic antibody and will be given every two weeks until progression or unacceptable toxicity develops.

Arm

Intervention/Treatment

Experimental: Dose Expansion

The dose expansion will consist of up to 20 subjects and the dose level of AMG 820 will be dependent upon emerging safety and PK data from the dose escalation part of the study.

Drug: AMG 820

AMG 820 is a fully human IgG2 c-fms antagonistic antibody and will be given every two weeks until progression or unacceptable toxicity develops.

Experimental: Dose Escalation

The dose escalation part of the study is aimed at evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of AMG 820.

Drug: AMG 820

AMG 820 is a fully human IgG2 c-fms antagonistic antibody and will be given every two weeks until progression or unacceptable toxicity develops.

Outcome Measures

Primary Outcome Measures

Area Under Curve (AUC) Time Frame: predose, 0.5, 1, 2, 4, 8, 24 hours post-dose [3 years]
Dose of AMG 820 where clinically significant or ≥ Grade 3 changes in safety laboratory tests, physical examinations, ECGs, or vitals signs in all subjects enrolled is greater than 33%. [3 years]
Change in tumor associated macrophages (TAMS) as assessed by tumor biopsy at 9 weeks. [3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Men or women ≥ 18 years old
Subjects must have a pathologically documented, definitively diagnosed, advanced solid tumor
Measurable disease per RECIST 1.1 guidelines
Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
Part 2 - Dose Expansion only: Subjects must have tumor tissue that is accessible for core needle biopsy by using minimally invasive procedures and must consent to undergo biopsies of the tumor
Able to fast 4 to 6 hours for FDG-PET/CT scan, except subjects with prostate or bladder cancers
Competent to sign and date an Institutional Review Board approved informed consent form
Adequate hematologic, renal and hepatic function as determined by laboratory blood and urine tests

Exclusion Criteria:

Men and woman of reproductive potential, unwilling to practice a highly effective method of birth control for the duration of the study and an additional 4 months after receiving the last dose of study drug.
Women who are lactating/breastfeeding or planning to become pregnant during the duration of the study
Primary central nervous system (CNS) tumors or CNS metastases
History of presence of hematological malignancies
History of arterial or venous thrombosis within 6 months of study enrollment
History of bleeding diathesis
Myocardial infarction within 6 months of study day 1, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or unstable cardiac arrhythmia requiring medication, or uncontrolled hypertension
Hypertension not adequately controlled with medication (diastolic > 90mmHG; systolic > 140 mmHG)
Left ventricular ejection fraction (LVEF) ≤ 50%
Active infection requiring (IV) antibiotics within 2 weeks of study enrollment
Known positive test for human immunodeficiency virus (HIV)
Known chronic hepatitis B or hepatitis C infection
Positive test for hepatitis B surface antigen or hepatitis C antibody
Known history of tuberculosis (TB), exposure to active TB-infected individuals, or positive TB skin test (tuberculin or purified protein derivative (PPD) test) upon study entry (subjects previously vaccinated for TB are not excluded unless there is evidence of active TB)
Anti-tumor therapy within 4 weeks of study day 1 including chemotherapy, antibody therapy, retinoid therapy, or other investigational agent
Concurrent or prior anticoagulation therapy within 28 days of study day 1
Major surgery within 28 days of study day 1
Any co-morbid medical disorder that may increase the risk of toxicity, in the opinion of the investigator or sponsor

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Philadelphia	Pennsylvania	United States	19111
2	Research Site	Greenville	South Carolina	United States	29605
3	Research Site	San Antonio	Texas	United States	78229